Search Results for: female sexual dysfunction

FDA Advisory Committee Recomends Approval Of Dynavax's Helplisav-b Vaccine

The FDA’s Vaccines and Related Biological Products Advisory Committee voted 12-1 (with 3 abstentions) that Dynavax Technologies’ Heplisav-B, a hepatitis B vaccine, is safe. The proposed indication is for immunization against infection caused by all known subtypes of hepatitis B virus in adults age ≥18. It would be administered in two 0.5 mL doses, given four weeks apart.

FDA Advisory Committee Unanimously Recommends Approval Of Gene Therapy For All

The FDA’s Oncologic Drugs Advisory Committee (ODAC) met to review the biologics license application for Novartis’ tisagenlecleucel-T (CTL-019), an intravenous CAR T therapy for treating pediatric and young adult patients (age 3-25) with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). The panel voted unanimously (10-0) that the benefits outweigh the risks, sending a strong message to the FDA in favor of approval. The FDA PDUFA date is October 3, 2017.

Transcatheter Valve Therapies (TVT)

Attendance at TVT was up ~20% this year. While there isn’t a lot going on with new transcatheter aortic valves beyond the move to intermediate-risk patients (and perhaps low-risk patients in the future), it is a busy space, with a multitude of other devices in development and generating excitement, including ~70 mitral valves, several tricuspid valves, embolic protection devices, and new imaging approaches. One of the themes running through the meeting was the need for a “full toolbox” of devices to treat patients.

American Urological Association (AUA)

Among the therapies discussed at AUA this year were: new therapies for benign prostatic hyperplasia, treatment of overactive bladder, prostate cancer tests and treatment, PD-1/L1 inhibitors for renal cell carcinoma and urothelial cancer, locally-delivered therapies for bladder and urothelial cancer, and robotic treatment of kidney stones.

ASCO-SITC Clinical Immuno-Oncology Symposium

There were no data or major announcements at this meeting. It was more of an Immunology 101 course, with most of the focus on the basics of immunotherapy for cancer. There was a lot of attention to CAR T therapies and biomarkers, though none of the many biomarkers being investigated has been able to show clear utility in predicting which patients will respond to immunotherapy drugs or even for monitoring patients on those agents. The role of the microbiome also came up frequently.

Angiogenesis, Exudation, And Degeneration

The Angiogenesis, Exudation, and Degeneration meeting, sponsored by Bascom Palmer Eye Institute, always offers a great overview of the status of research in retinal diseases. And there is a long list of drugs/therapies in development to treat retinal diseases, but there isn’t anything on the near horizon that experts believe will be a game changer.

International Symposium On Endovascular Therapy (ISET)

This meeting, attended mostly by interventional radiologists and vascular surgeons, provided a good opportunity to review the therapies available and in development to treat peripheral artery disease, pulmonary embolisms (PEs), and aortic aneurysms -- atherectomy devices, drug-coated balloons, stents (bare, drug-eluting, and covered), aspiration devices, embolic protection, and more. There wasn’t much breaking news, but the meeting offered an overview of trends in device usage. There was even an update on new percutaneous cardiovascular devices.

American Heart Association Scientific Sessions

The annual American Heart Association (AHA) meeting was packed with clinical trials, including a number of surprises. There were too many to cover all of them, but here are some of the highlights of the meeting, reporting on COX-2 inhibitors, fractional flow reserve (FFR), left ventricular assist devices (LVADs) for heart failure, lipids, novel oral anticoagulants (NOACs), transcatheter aortic valve replacement (TAVR), and more.

Transcatheter Cardiovascular Therapeutics (TCT)

TCT was very data-packed this year. The news on Absorb Absorb, a bioabsorbable stent, was disappointing. New drug-eluting stents are having a hard time competing with existing drug-eluting stents. Use of Boston Scientific’s Watchman LAA closure device is increasing, but there are several competitors on the horizon. Spectranetics’ Stellarex drug-coated balloon will be third to market, but it is likely to be a strong contender. Endologix’s Nellix is off the European market due to a migration problem, and that could delay approval in the U.S. In TAVR, Medtronic’s CoreValve Evolut R pivotal data were positive, but Boston Scientific’s Lotus continues to have a high rate of new pacemakers. The migration to intermediate-risk patients should not be a problem for TAVR, but low-risk patients may be more of a challenge, especially younger patients. Even though industry would like it as a way to spur innovation, CMS is unlikely to change its policy of not paying for devices until they are proven.

Bulletin: Donald Trump And Healthcare

What would a Donald Trump presidency mean for healthcare? The candidate hasn’t revealed much about his plans, but this report pulls together what he's said officially as well as what experts predict that will mean for the FDA, hospitals, drug and device development, individuals, and more.

European Society Of Cardiology

There were many trials and data presented at the European Society of Cardiology meeting but no really dramatic news. Yet, it was an opportunity to take the pulse of U.S. and European doctors on adoption of new drugs and the outlook for some pipeline drugs. Among the topics reviewed in this report: the U.S. and European uptake of PCSK9 inhibitors for hypercholesterolemia and Novartis’ Entresto for heart failure; a look at data on several other cardiac drugs; some details on Portola Pharmaceuticals’ AndexXa, a Factor Xa inhibitor reversal agent which the FDA rejected; trends in cardiovascular drug development; new European guidelines for dyslipidemia and atrial fibrillation; and, last but not least, data on cardiac devices such as ICDs, CPAP, bare metal stents vs. drug-eluting stents, and Accumetrics’ VerifyNow platelet reactivity test.

FDA Moves To Keep Zika Out Of U.S. Blood Supply

The FDA is requiring that all blood donated in the U.S. be tested for Zika virus infection using one of two RNA tests that are still investigational. In this report, the FDA answers some questions about this action.

FDA Advisory Committee Recommends Approval Of Valeant's Siliq (Brodalumab) To Treat Psoriasis

An FDA Advisory Committee voted unanimously to recommend approval of Valeant Pharmaceuticals’ Siliq (brodalumab), an anti-IL-17 to treat moderate-to-severe plaque psoriasis, determining that the drug is effective, with safety “concerns” related to suicidality, but not enough to withhold the drug from patients. However, more than a third of the panel recommended a mandatory registry, and a few would like to see a postmarketing trial evaluating suicidality. However, the panel dismissed concerns about a cardiac signal.

Transcatheter Valve Therapeutics (TVT)

Interventional cardiologists are anxious for FDA approval of TAVR in intermediate-risk patients, but there is no waiting list of patients.  The durability of TAVR is a concern, but it is not much worse than surgical valves.  Patients may need to be followed for ≥10 years with TAVR, but a valve-in-valve procedure is an option if there is a failure.  And the durability issue will not delay FDA approval of new valves  Leaflet thickening also is a problem, but again, not a technology killer, just more monitoring and perhaps warfarin for life in some patients.  Endocarditis has probably been an under-appreciated complication.  To get the cost down, some centers are taking a minimalist approach.  As more valves become available, mMost U.S. centers expect to use 2-3 of them only, most likely Sapien, CoreValve, and Lotus (now that the pacemaker rate is starting to come down).  The outlook for other valves is murkier, unless they win on price.

International Workshop on NASH Biomarkers

While there is a lot of work going on to find a biomarker for use in NAFLD and NASH, the efforts are fragmented, competitive instead of collaborative, and early. The lack of any regulatory input at this conference didn’t help. It is clear the field still has a long way to go to identify patients and stage them, much less monitor response to drug therapy. And with outcomes trials likely to be necessary, it may be years before a biomarker is ready for prime time.

FDA Advisory Committee Recommends Approval of Intercept’s Drug for PBC

The FDA’s Gastrointestinal Drugs Advisory Committee voted unanimously (17-0) to recommend accelerated approval of Intercept Pharmaceuticals’ obeticholic acid (OCA) in combination with ursodeoxycholic acid (UDCA) for adults with primary biliary cirrhosis (PBC) who don’t respond well enough or who cannot tolerate UDCA.

American Academy of Dermatology (AAD)

Cosmetic dermatology procedures are holding pretty steady, but there is less interest in expensive new lasers. Dermatologists who have started using Allergan’s Kybella are generally pleased with the results, and use is expect to continue to increase but not negatively affect use of Zeltiq’s CoolSculpt. ♦ In toxins, Revance Therapeutics’ daxibotulinumtoxinA (RT-002) might last longer than Allergan’s Botox, but the data weren’t convincing, and there are dosing and ptosis issues. ♦ Valeant’s “bad boy” pricing image is causing dermatologists to try to avoid its products. ♦ In acne, Novan Therapeutics’ SB-204 looks promising. ♦ In atopic dermatitis, both Anacor’s crisaborole and Chugai’s nemolizumab look promising. ♦ In psoriasis, the excitement is over IL-17 inhibitors. The estimate is for ≥12% of patients to be on an anti-IL-17 in a year. Novartis’ secukinumab was first to market, but Lilly’s ixekizumab offers slightly easier dosing.

International Symposium on Endovascular Therapy (ISET)

Atherectomy use is flat to slightly down. ♦ Use of both bare and drugeluting stents is down, though Boston Scientific’s Eluvia could give drug-eluting stents a boost. ♦ Use of drug-coated balloons (DCBs) is increasing, and they are being combined with atherectomy. ♦ The choice between C. R. Bard’s Lutonix and Medtronic’s Admiral is often dictated by hospital buying contracts, lesion length, and doctor experimentation. Reports of powdered drug coming off of Admiral DCBs raised some eyebrows at the meeting. ♦ Device pricing appears to be holding steady, at least for now. ♦ Endologix’s Nellix appears to be a promising new way to treat aneurysms. ♦ Penumbra’s Indigo is getting attention for treating embolisms.

Zika Virus Update

Zika is getting worse in the U.S., not just through travel but also through sexual transmission, and pregnancies are being affected. In a teleconference with reporters, Thomas Frieden, MD, MPH, director of the Centers for Disease Control and Prevention (CDC), Denise Jamieson, MD, MPH, a captain in the U.S. Public Health Service (USPHS) and co-lead of the CDC’s Pregnancy and Birth Defects Team, CDC Zika Virus Response Team, and other government officials provided an update on the Zika virus situation.

Bulletin: Zika Virus Update

In a teleconference with reporters, Thomas Frieden, MD, MPH, director of the Centers for Disease Control and Prevention (CDC), reviewed what is known about Zika and the latest recommendations. The bottom line: The CDC’s priority is to prevent infection in pregnant women, “Spread in other populations is much less a concern because 4 of 5 Zika infections are asymptomatic, and the symptoms are generally mild...The real effect is on development of the brain of the fetus.”

Zika Virus Update

In a teleconference with reporters, government officials discussed the status of the Zika virus outbreak – what they know, what they don’t know, and what they want to find out.

2016 Genitourinary Cancers Symposium

Prostate cancer: · Docetaxel is being used earlier. · Doctors are splitting use evenly of abiraterone and enzalutamide. · There are reports of an increasing issue with neurotoxicity with enzalutamide, opening the door for Johnson & Johnson’s ARN-509 if it has less toxicity. · PARP inhibitors are promising but PD-1 inhibitors have little effect. · Hypofractionation is catching on but reimbursement is holding use back. · Use of both diagnostic and prognostic genomic testing is increasing slowly. ♦ Renal cell carcinoma: · Use of Bristol-Myers Squibb’s Opdivo is quickly catching on but sequencing it with Exelixis’ cabozantinib is uncertain, pending survival data from the METEOR trial. ♦ Urothelial cancer:  Checkpoint inhibitors appear very effective, and as soon as one is approved, it will get widespread use.

European Society of Cardiology (ESC)

There were some positive studies, even more negative news, and a few neutral reports at this year’s European Society of Cardiology meeting. For details, see: ♦ Anticoagulation . . . . . . Page 2 (NOACs and Factor Xa inhibitors and antidotes) ♦ Heart failure . . . . . . . . . Page 4 (Novartis’ Entresto) ♦ PCSK9 inhibitors . . . . . Page 6 (Sanofi and Regeneron’s Praluent and The Medicines Company and Alnylam’s ALN-PCSsc) ♦ CETP inhibitors . . . . . . Page 11 ♦ Miscellaneous drugs . . Page 12 (The Medicines Company’s Angiomax, Merck’s Januvia, Sanofi’s Lyxumia) ♦ Gene therapy . . . . . . . . Page 14 ♦ Medical devices . . . . . . Page 14 (Abbott’s Absorb, Abiomed’s Impella, ResMed’s VPAP, St. Jude Medical’s FFR and Nanostim)

American Headache Society (AHS)

Neurologists are excited about CGRP inhibitors. Use is likely to be limited mostly by cost and insurance coverage. Four CGRP inhibitors are in a dead heat to be first-to-market. All appear safe and effective, and there is very, very little that differentiates them. ♦ Most neurologists already are trained in doing injections of Allergan’s Botox for chronic migraine. Insurance coverage for on-label use is good if patients first fail several drugs. ♦ CGRP inhibitors are expected to impact use of Botox, but just a little (from 13% of patients now to 11% in 2020). ♦ Doctors remain excited about Allergan’s Semprana (formerly Levadex), and they hope it will finally become available. ♦ CoLucid Pharmaceuticals’ lasmiditan will be useful for the growing number of patients who can’t take a triptan for cardiac reasons. ♦ Perhaps PFO closure for migraine is finally dead, with the trial failure of St. Jude Medical’s Amplatzer.

American Academy of Dermatology

Aesthetic procedure volume is relatively flat, and few dermatologists are buying any big-ticket items this year. ♦ Actavis/Allergan’s Botox and dermal fillers remain hot, while ablative lasers have cooled off, but the real excitement is over Kythera’s ATX-101 for submental fat, which will do very well if it isn’t over-priced. ♦ In atopic dermatitis, doctors expect to use Anacor’s AN-2728, a topical therapy, and will reserve Sanofi and Regeneron’s dupilumab, a systemic therapy, for a niche group of severe patients. ♦ Several new drugs are in development for psoriasis, but the choice may be dictated by insurers. ♦ In onychomycosis, Valeant’s Jublia has caught on much faster, and is substantially less expensive, than Anacor and Novartis’ Kerydin.

Endocrine Society’s ENDO 2015

Investigational drugs abounded at ENDO 2015, from 7 long-acting growth hormones to a new treatment for secondary hyperparathyroidism (SHPT) and the first enzyme replacement therapy for hypophosphatasia (HPP). In addition, use of the new obesity drugs appears to be increasing, though endocrinologists aren’t very excited about them and cost is limiting patient interest. Insulin pumps, however, are popular for Type 1 diabetics, though still underutilized.

Society for Immunotherapy of Cancer

Combination therapy will contribute to the success of T cell therapy. The most experience is with anti-CTLA-4, although anti-PD-1 is promising. ♦ There have been complete and lasting responses in patients with metastatic melanoma given autologous TILs and IL-2. ♦ CAR therapy is promising in ALL, but severe cytokine response syndrome is a challenge. ♦ OX40 antibodies do not work alone, but they do work well in combinations. ♦ CD137 is promising, and Pfizer has launched an anti-CD137 program. ♦ The CD40 antibody may be promising as monotherapy as well as in combination.

FDA Public Workshop on Female Sexual Dysfunction

An FDA public meeting on female sexual dysfunction gave women an opportunity to describe what this problem means to them personally and how it affects their life. The meeting also may help the FDA formulate some new guidelines for drug development for this condition, particularly trial endpoints and measures.

Heart Failure Society of America

LVAD use is growing at a steady ~5%- 10%/year, and it is expected to continue at the same pace, driven by the prospect of smaller, more durable devices used in less sick patients. Doctors see no slowdown in the U.S. market and no dips/surges. ♦ Pump thrombosis continues to be a mystery, but patient management may be the key. At some hospitals, it spiked and then returned to normal levels. At others it remains elevated. ♦ Thoratec’s HeartMate II is easier to explant but more prone to thrombosis. HeartWare’s HVAD is smaller and easier to implant but has more strokes. So, it really comes down to physician preference. The results of the ongoing head-to-head ENDURANCE trial could be critical to the choice of device, but doctors describe them as fairly interchangeable. ♦ The positive news: Pumps are improving, and survival is improving. ♦ The negative news: The devices continue to be plagued by adverse events – pump thrombosis, GI bleeding, infections, and stroke – so they are not really ready for use in less sick patients. ♦ New devices are on the horizon, but the holy grail is a fully implantable pump, with no drivewires and a long-lasting battery.

Ebola Update October 12, 2014

A healthcare worker in Texas, a female nurse who cared for Thomas Duncan (U.S “patient zero”), the Ebola patient from Liberia, has tested positive for Ebola. The nurse provided care to Duncan on multiple occasions, and it included “extensive contact.”

FDA Advisory Committee Recommends Approval of Novo Nordisk’s Liraglutide for Obesity

Another diet drug moved a step closer to FDA approval, with the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voting 14-1 to recommend approval of Novo Nordisk’s Saxenda (liraglutide 3.0 mg) to treat obesity. For diabetes, liraglutide is sold as Victoza (1.8 mg), but it was given a new name and dosage for obesity.

American Urological Association

For overactive bladder, Allergan’s Botox is the first choice after anticholinergics. Uroplasty’s Urgent PC is an interesting option but requires too many patient visits, and they implant Medtronic’s InterStim as a last resort. The treatment to watch, though, is Lipella’s Lipo-BoNT. ♦ There is interest in Auxilium’s Xiaflex for Peyronie’s disease, but urologists are taking a cautious approach and warned that uptake will depend on insurance coverage. ♦ For metastatic castration-resistant prostate cancer urologists prefer Johnson & Johnson’s Zytiga over Astellas and Medivation’s Xtandi, and there is little interest in Dendreon’s Provenge. The cost of new tests and lack of insurance coverage is discouraging urologists from using them.♦ Urologists are not concerned about the cardiac safety of testosterone supplementation, use is expected to go up, and the preference is for topical formulations because of cost. However, an oral testosterone without adverse liver effects would be a game changer.

Finding a Regulatory Pathway for Antidotes for Anticoagulants

The FDA is anxious for an antidote to the novel oral anticoagulants to be approved in the hope that it will help get more people who need an anticoagulant to take one. Antidotes may be able to be approved through the FDA’s accelerated approval pathway.  The FDA is likely to accept data from healthy volunteers in lieu of a randomized trial in patients, provided there are enough volunteers studied.  A postmarketing registry is likely to be mandated to monitor for unexpected safety issues. At least one antidote developer believes there is now “light at the end of the tunnel.”

International Liver Congress of the European Association for the Study of the Liver

Hepatologists are excited about the array of new drugs becoming available to treat HCV, but cost is a huge concern and a limiting factor. New WHO and EASL guidelines recommend using the costly new drugs for the most severe patients. ♦ Thus, while the number of patients treated is going up, there will still be plenty of patients for newer agents on the near horizon – provided screening increases and there really are as many undiagnosed patients as projections indicate. ♦ Gilead’s Sovaldi has the lead, but three other companies are likely to have highly effective all-oral regimens on the market soon: AbbVie, Bristol-Myers Squibb, and Merck. The differences are relatively minor, so market share may be dictated by marketing, pricing, and payors. However, each may have an advantage in some subgroup. ♦ Intercept’s obeticholic acid is showing promising results for primary biliary cirrhosis.

AF Symposium 2014

Atrial fibrillation procedure volume is expected to increase in 2014 at the same rate as 2013. ♦ Medtronic’s Arctic Front cryoballoon for AF ablation is gaining popularity quickly. ♦ Among hybrid ablation procedures, the highest interest is a combination of a traditional endocardial catheter ablation and an epicardial procedure, done entirely by an EP in the EP lab. ♦ New ablation navigation systems are interesting but won’t be ready for prime time for at least 2-3 years. ♦ Novel oral anticoagulants are catching on gradually, with use limited by a number of factors, including cost, lack of a reversal agent, switching issues, cardioversion, timing, etc. ♦ Demand for Boston Scientific’s Watchman, a left atrial appendage closure device, is expected to be very strong. ♦ EPs are not ready to give up on renal denervation.  

2014 Genitourinary Cancers Symposium

Oncologists and urologists were impressed with the PREVAIL data on Astellas and Medivation’s Xtandi in pre-chemotherapy metastatic castration-resistant prostate cancer, in terms of survival, chemotherapy delay, and PFS, making it seem similar to Johnson & Johnson’s Zytiga – all without the steroid requirement. ♦ Xtandi won’t expand the number of patients on treatment because that market is fairly saturated. Xtandi is expected to capture 65% of the market, with Zytiga falling to 35%. ♦ How best to sequence prostate cancer drugs is still a moving target. Xtandi after Zytiga, or vice versa, only adds an extra ~3 months of benefit. Combining Xtandi and Zytiga is a possibility but, because of cost, is unlikely to happen until and unless trial data show benefit. ♦ There is no indication that use of Dendreon’s Provenge is likely to increase. ♦ Doctors using Bayer and Algeta’s Xofigo report very good results, and it is likely to slowly gain use.

FDA Advisory Committee Recommends Approval of Boston Scientific’s Watchman

The FDA’s Circulatory System Devices Advisory Committee voted 13-1 that Boston Scientific’s Watchman, a left atrial appendage closure device, is safe, effective, and has a positive risk:benefit for use in preventing stroke in patients with atrial fibrillation.

FDA Advisory Committee Does Not Recommend Approval of Sanofi/Genzyme’s Lemtrada for Multiple Sclerosis

The FDA’s Peripheral and Central Nervous System Drugs Advisory Committee sent a mixed message to the FDA about Sanofi/Genzyme’s Lemtrada (alemtuzumab) for multiple sclerosis. The panel decided the clinical trials were not adequate, and the drug did not impact disability. The panel voted that the drug was effective, but the FDA said the panel couldn’t say that if the trials were inadequate. The panel also said the drug is safe, but it should not be a first-line therapy, if approved.

FDA Advisory Committee Recommends Approval of Biomarin’s Vimizim for Morquio A Syndrome

The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted to recommend approval of BioMarin Pharmaceutical’s Vimizim, an enzyme replacement therapy to treat Morquio A syndrome, a rare congenital metabolic disorder that affects bone development, growth, and movement. The only controversy may be the participation of a panel member whose child is successfully being treated with the drug.

Obesity Week

Uptake of brand obesity medications is relatively slow but expected to gradually improve. The key issues are cost and lack of insurance coverage, but physician unfamiliarity with them, attitudes about obesity, and fear of another late-occurring fen-phen-type adverse event also play a role. ♦ Employers are reluctant to cover obesity medications, even as part of a wellness program, and that is not expected to improve substantially in the near term. ♦ Use of Vivus’ Qsymia outpaces Arena and Eisai’s Belviq because it was approved first and has more insurance coverage, but obesity specialists expect use to begin to even out. ♦ Zafgen’s beloranib could be the game changer if the data hold up in Phase III. It produces rapid and significant weight loss with a once-every-twoweek injection. ♦ Two devices in development may help people lose weight, but it is hard to believe anyone would use them.

FDA Subcommittee Discusses Pediatric Trials of Cancer Biologics

The pediatric oncology subcommittee of the FDA’s Oncologic Drugs Advisory Committee (ODAC) agreed with the goal of speeding pediatric trials of PD-1 inhibitors, and the FDA is nudging Bristol-Myers Squibb and Merck to move faster. The panel also praised Novartis for its pediatric studies of LEE-011, a CDK4/6 inhibitor.

FDA Advisory Committee Recommends Approval of Gilead Sciences’ Sofosbuvir to Treat Hcv

The FDA’s Antiviral Drugs Advisory Committee voted unanimously (15-0) that Gilead Sciences’ sofosbuvir, an NS5B polymerase inhibitor, should be approved in an all-oral combination with ribavirin to treat HCV-2/3 patients.  And the panel voted unanimously (15-0) that it should be approved in combination with interferon and ribavirin for treatment-naïve HCV-1/4 patients.

FDA Advisory Committee Recommends Approvalof J&J And Medivir’s HCV Drug Simeprevir

The FDA’s Antiviral Drugs Advisory Committee voted unanimously (19-0) that the benefits of Johnson & Johnson/Janssen Pharmaceuticals and Medivir’s simeprevir, given in combination with pegylated interferon and ribavirin (PR), outweigh the risks for HCV-1 patients. The question is how many patients will be interested in another protease inhibitor regimen with PR when all-oral therapies are coming soon. However, the panel was acutely aware that simeprevir could become part of the first all-oral, interferon-free regimen through offlabel use with Gilead Sciences’ sofosbuvir, even though that use was not an issue before the panel.,

Heart Failure Society of America (HFSA)

Doctors are very optimistic about  Novartis’ serelaxin for acute heart  failure.  Doctors are less familiar with  Novartis’ LCZ-696, a combination of  valsartan and AHU-377, a neprilysin  inhibitor, for chronic heart failure  patients, but those who know about it  said that it is potentially very  interesting.  If both Novartis drugs are successful,  doctors predicted they will be  blockbusters, but the enthusiasm was  tempered by the history of heart  failure drug failures.  LVAD use is up slightly, with doctors  predicting an average 11%  increase this year vs. last year.  Not having approval for destination  therapy is limiting use of HeartWare’s  LVAD, and use will increase if it gains  that approval.  While HeartWare’s LVAD has higher  bleeding and clotting risks and needs  more aggressive  anticoagulation,  doctors are concerned about a possible  increase in pump thrombosis over the  past four years with Thoratec’s  HeartMate II, though no one really knows why that has occurred.

FDA Advisory Committee Rejects Expanded Indication for Amarin’s Vascepa

The FDA’s Endocrinologic and  Metabolic Drugs Advisory  Committee voted 9-2 that the FDA  should  not expand the label for  Amarin Pharmaceuticals’ Vascepa  to allow treatment of patients with  moderately-high triglycerides  ( ≥ 200 mg/dL to <500 mg/dL) and  mixed dyslipidemia who are already  on a statin. Panel members said  that any decision should wait until  the ongoing REDUCE-IT  cardiovascular outcomes trial is  completed.

American Neurological Association (ANA)

Alzheimer’s disease. Neurologists are  hopeful that Merck’s MK-8931, a BACE  inhibitor, will work, but a failure could  seriously set the field back.  nALS.  Neurologists are cautiously optimistic  about Cytokinetics’ tirasemtiv and Isis’  ISIS-333611, an SOD1 inactivator, for  symptoms, about Neuralstem’s NSI-566, a  stem cell therapy, and about an Isis C9orf72  mutation blocker for extending survival.   Multiple sclerosis.  Adverse events are  worse in practice than in clinical trials with  Biogen Idec’s Tecfidera, and Teva’s  laquinimod, if and when it is approved,  may do better than expected.  Orphan neurological diseases. ALD –  Skepticism about Bluebird bio’s  Lenti-D.  TTR/FAP –  Excitement about  diflunisal, a generic NSAID.  DMD –  Both GSK’s drisapersen and  Sarepta’s eteplirsen expected to work,  and too early to say which is better.  MG – Alexion’s Soliris and Roche/  Genentech’s Rituxan are promising.  Myositis –  Watch Orphazyme’s  arimoclomol and Novartis’ siponimod.  NMO – Alexion’s Soliris looks very  promising, but cost will limit use.  SMA – Isis and Biogen Idec’s ISIS- SMNRx may work in a subset of patients,  but the excitement is with gene therapy.

 

European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)

ECTRIMS may issue guidelines this year on  choosing among the available MS drugs.  ♦ Neurologists predicted that in 1 year, <5% of  patients on an oral agent would be on Sanofi/  Genzyme’s Aubagio, ~5% on Novartis’ Gilenya,  and 16% on Biogen Idec’s Tecfidera. Teva’s  laquinimod is expected to have limited, non- first-line use, but doctors are intrigued with the  brain atrophy data.  ♦ U.S. doctors said ~30% of real-world  Tecfidera patients have intolerable flushing or  GI side effects, and half of these discontinue.  ♦ European doctors are excited about Tecfidera  and are warehousing patients for it, and they  will be  very unhappy if it isn’t launched in  Europe. But there are other fumarates in devel- opment, including Forward Pharma’s FP-187.  ♦ Doctors have adjusted to the PML risk with  Biogen Idec’s Tysabri. There is little worry  about PML with Gilenya or Tecfidera.  ♦ Neurologists expect Sanofi/Genzyme’s  Lemtrada to be a niche treatment, given at  select centers primarily to Tysabri failures.  ♦ Second-generation S1P  receptor modulators  may have improved safety profiles vs. Gilenya,  but experts are not convinced that they won’t  have cardiovascular side effects or will avoid a  class warning or first-dose monitoring.  ♦ Doctors are fairly excited about anti-CD20  therapies, especially Roche/Genentech’s  ocrelizumab, but the advantages of ocrelizumab  over Rituxan are not clear. 

European Society of Cardiology: Drugs

Use of novel oral anticoagulants is expected to increase, with newer ones taking share from the less new ones. ♦ Three antidotes are in development for oral anticoagulants, and Perosphere bears special attention. ♦ PCSK9 inhibitors continue to look promising for lowering very high cholesterol, but the different agents are not well differentiated. ♦ Data appear to confirm the cardiovascular safety of DPP-4 inhibitors. ♦ Evidence continues to mount that raising HDL is not helpful, even though low HDL is a risk marker. ♦ Experts were underwhelmed with data on The Medicines Company’s cangrelor. ♦ Drugs continue to struggle to show a benefit in heart failure, but there is still hope.

European Society of Cardiology: Devices

Use of coronary thrombus aspiration devices may decrease after a study showed no mortality benefit with Medtronic’s Export.  Leadless pacemakers are intriguing and may be the future, with Boston Scientific/Cameron and Nanostim leading the way.  LVAD use may be steady in Europe, but in the U.S. doctors predicted a 12% increase in the next year. The HeartWare and Thoratec devices are considered very similar, and doctors want both companies in the game.  TAVR volume is increasing in Europe, but there is little interest in newer valves outside of Germany and Switzerland, but doctors are very interested in Boston Scientific/Sadra’s Lotus.  Interest in renal denervation is growing in Europe, but the realworld results may not be as good as in the trials.

American Psychiatric Association

Device therapy for severe depression is effective, but it is used sparingly. ♦ ECT remains the most common device therapy. ♦ TMS is catching on but slowly, limited by cost, lack of reimbursement, and a need for more data. ♦ Psychiatrists estimated that ~6% of their patients are eligible for device therapy but only about half get it. ♦ Neuronetics’ NeuroStar is the only TMS currently being used, but psychiatrists are interested in Brainsway’s Deep TMS. ♦ TMS is reserved for patients failing antidepressants, which are generally continued during TMS treatment. ♦ Proponents said that the benefits of TMS can last up to 6 months or more post-treatment, but few would give patients a second course. ♦ TMS is likely to negatively impact use of Cyberonics’ VNS, but VNS is expected to continue to have a niche role.

American Congress of Obstetricians and Gynecologists

Up to 30% of American women have endometriosis, with ~9% needing treatment, usually oral contraceptives, GnRH agonist injections, or surgery. New drugs, like Neurocrine Biosciences and AbbVie’s elagolix, an oral GnRH agonist, have an opportunity, but doctors know little about elagolix and worry about compliance and side effects.  ~30% of women have fibroids, with a third of them candidates for new therapies like Repros’ Proellex, a vaginal SPRM, but Proellex is seen as more of a new delivery method than a new drug. Doctors didn’t know much about it but thought it might be another useful option. Use of Intuitive Surgical’s da Vinci robot for gynecological surgery is flat to slightly up, but use is likely to increase in the future, with hospitals pressured to buy more robots and doctors to use them. Training is becoming a critical issue as is the realization that not every doctor should be doing robotic procedures. Non-invasive prenatal testing is viewed as a huge breakthrough and will be used in low-risk as well as high-risk women in the next few years, but it is seen as basically a pre-test for amniocentesis and should not be used diagnostically.

American Urological Association (AUA)

A growing shortage of urologists means patients may have to wait longer and longer to be seen and treated.  Urologists are anxious to find ways to better select prostate cancer patients for treatment so that fewer are overtreated, and they hope that will encourage more screening. J&J’s Zytiga is the big winner in the new AUA prostate cancer guidelines, but those guidelines are expected to be changed quickly as new drugs get approved. Urologists predicted that Medivation and Astellas’ Xtandi will be used ahead of Zytiga in most cases when it gets a pre-docetaxel label. There was very little interest in Sanofi’s Jevtana, but there is a fair amount of enthusiasm for Bayer’s Xofigo (radium-223). Immunotherapy for prostate cancer with Dendreon’s Provenge is growing slowly but steadily. Interest in molecular diagnostic testing is growing, but doctors don’t know which test to use, and cost and reimbursement are issues. Men are very interested in treating low testosterone (hypogonadism), but cost is a barrier; the negative effect on sperm count is only an issue for a real minority of patients

American Academy of Neurology (AAN)

Biogen Idec’s Tecfidera (BG-12) is poised for a very successful launch as the third oral multiple sclerosis drug, but dropouts may be higher than in clinical trials due mostly to GI toxicity but also to flushing. Low body weight appears to put users of Biogen Idec’s Tysabri at higher risk of PML, so some experts are recommending those patients get it every 6 weeks instead of monthly. Use of Novartis’ Gilenya is expected to hold fairly steady. Initiation is a hassle, but doctors are getting more comfortable with its safety profile. Some big gun drugs also look very promising in MS, and the data continue to be positive: Biogen Idec’s daclizumab, Sanofi/Genzyme’s Lemtrada, and Roche/Genentech’s ocrelizumab. Biogen Idec’s Plegridy (pegylated Avonex) is expected to cannibalize Avonex and perhaps give a little life to injectables in face of the oral threat. There was a mish mash of news on other neurological conditions, but nothing dramatic.  

FDA Advisory Committee Recommends Approval of Abbott Vascular's MitraClip

Abbott’s MitraClip is approved and used in Europe to treat mitral regurgitation, but the outlook at the FDA remains cloudy. The FDA’s Circulatory System Devices Advisory Committee did not send the FDA a definitive message about approvability, voting 5-3 that the benefits outweigh the risks. The panel voted unanimously that it is safe, but split the other direction (4-5) on efficacy.

American Academy of Dermatology (AAD)

Traffic was slightly down in the exhibit hall, but sessions on hot topics were generally packed. ♦ Merz’s Xeominis is expected to gain market share but how much will depend on marketing.  All three toxins are viewed as comparable in efficacy, with Xeomin cheaper but Allergan’s Botox having the name recognition.  ♦ Use of facial fillers is flat, but doctors are excitedly awaiting Allergan’s Juvéderm Voluma. ♦ The laser market is still challenging, but laser company executives claim they are seeing a little pickup and are optimistic. ♦ Celgene’s apremilastmet the primary endpoint in a Phase III trial, but the results were disappointing to dermatologists, who predicted it will be a niche product unless it is priced low enough to drive use. ♦ Dermatologists believe biologics are the future for psoriasis patients, particularly anti-IL-17s.

Cardiovascular Research Technologies (CRT) 2013

TAVR continues to gain momentum, but there are concerns about cost, hospitals losing money on the procedure, and how quickly smaller hospitals will start implementing it. On average, except for a few centers, most hospitals are doing fewer than 5 TAVRs a month.  ♦  Renal denervation (RDN) seems to work for hypertension, but about 10%-20% are nonresponders. Some doctors are looking at applying it to other conditions.  ♦  There is high interest in bioabsorbables, but doctors agree that more long-term data are needed.  ♦  Doctors are extremely interested in drug-eluting balloons.

Advances in Genome Biology and Technology (AGBT)

Lab budgets are under pressure, but there is generally still money for sequencing machines.  ♦ Illumina’s MiSeq, and to a lesser extent HiSeq, are break-down prone, but scientists still really like the instruments.  ♦ Life Technologies’ Proton is generating interest, but it isn’t delivering on its promises – yet, and the company is pushing labs to buy multiple machines, which is meeting resistance.  ♦ Interest in single-cell analysis is high, and Fluidigm has created a niche, but there is competition from numerous companies and approaches.  ♦ Oxford Nanopore kept a low profile and offered no explanation for not delivering on last year’s promises of thumb drive size sequencers and 15-minute runs.  ♦ Labs are still buying PacBio RSs from Pacific Biosciences for their long reads, but they have pretty much given up on Roche 454s.

MEDCAC Rejects Beta-Amyloid PET Imaging for Alzheimer’s Disease

CMS is unlikely to change its noncoverage decision on PET imaging of brain beta-amyloid based on the findings of the MEDCAC. ♦ MEDCAC had low confidence that PET imaging of brain beta-amyloid changes outcomes in Alzheimer’s disease patients with early disease. ♦ The panel also said they had high confidence that the data are applicable to Medicare beneficiaries. ♦ Despite a long list of experts, all but one of whom urged coverage and stressed the value of PET-amyloid imaging, the panel was not convinced.

Angiogenesis, Exudation, and Degeneration 2013

Questions have been raised about the safety of “too much” VEGF inhibition – retinal thinning, ciliary body damage, intraocular pressure decreases, and geographic atrophy. ♦ Use of Regeneron’s Eylea continues to increase. ♦ If Allergan’s DARPin, a longer-acting VEGF inhibitor, really lasts even 3 months, it is expected to take share from Eylea the way Eylea has from Roche/Genentech’s Lucentis. ♦ The FDA has given approval for a Phase III trial of Ophthotech’s Fovista, a PDGF inhibitor that boosts the efficacy of VEGF inhibition. The trial design is being finalized, but it will start soon. ♦ A Phase II trial of Roche/Genentech’s Lucentis Reservoir is expected to start soon. Experts insisted temperature is not an issue. ♦ Doctors are optimistic that in DME Eylea will work as well as Lucentis and will get approved, but Avastin is not perceived as working as well.

American Academy of Cosmetic Surgery (AACS)

2013 is starting off a little slow for cosmetic surgeons, and many are delaying big ticket purchases or buying very selectively, but most are optimistic that things are getting better. ♦ Fillers, toxins, liposuction, and breast implants are hot, while interest in nonablative lasers – and anything without proven results – is down. ♦ There is no pent up demand for Allergan's Voluma ahead of FDA approval. ♦ Allergan's Botox is losing some share to Valeant/Medicis¡¦ Dysport. Merz's Xeomin is likely to pick up share but slowly. ♦ Doctors are very dubious about Kythera's ATX-101, an injection therapy for submental fat because it is too similar to the controversial mesotherapy. Mostly users will be doctors still doing mesotherapy. FDA approval is less important than might be expected, but it will help. ♦ Breast implant procedures are up, and silicone implants are gaining popularity, held back mostly by cost. ♦ Autologous fat is very, very popular, and some doctors are using it for stem cell procedures, but marketing that remains somewhat controversial

FDA Advisory Committee Recommends Approval of J&J’s Invokana (canagliflozin)

The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 10-5 to recommend approval of Johnson & Johnson/Janssen’s Invokana, an SGLT2 inhibitor for Type 2 diabetes, despite safety concerns. ♦ The panel was concerned with cardiovascular safety, bone fractures, and efficacy/safety in renally impaired patients but not enough to block approval. ♦ It appears likely that the FDA will approve Invokana but will require postmarketing studies and may limit use in renally impaired patients.

American Academy of Cosmetic Surgery (AACS)

2013 is starting off a little slow for cosmetic surgeons, and many are delaying big ticket purchases or buying very selectively, but most are optimistic that things are getting better. ♦ Fillers, toxins, liposuction, and breast implants are hot, while interest in nonablative lasers – and anything without proven results – is down. ♦ There is no pent up demand for Allergan’s Voluma ahead of FDA approval. ♦ Allergan’s Botox is losing some share to Valeant/Medicis’ Dysport. Merz’s Xeomin is likely to pick up share but slowly. ♦ Doctors are very dubious about Kythera’s ATX-101, an injection therapy for submental fat because it is too similar to the controversial mesotherapy. Mostly users will be doctors still doing mesotherapy. FDA approval is less important than might be expected, but it will help. ♦ Breast implant procedures are up, and silicone implants are gaining popularity, held back mostly by cost. ♦ Autologous fat is very, very popular, and some doctors are using it for stem cell procedures, but marketing that remains somewhat controversial

San Antonio Breast Cancer Sympoium

0332991, a CDK4/6 inhibitor, more than tripled survival in ER+/HER2- breast cancer. ♦ Investigators insisted that pretreatment can prevent the diarrhea with Puma Biotechnology’s neratinib, but experts insisted it has to prove some clear advantage to carve out a niche. 0332991, a CDK4/6 inhibitor, more than tripled survival in ER+/HER2- breast cancer. ♦ Investigators insisted that pretreatment can prevent the diarrhea with Puma Biotechnology’s neratinib, but experts insisted it has to prove some clear advantage to carve out a niche. ♦ Doctors are anxious for FDA approval of Roche/Genentech’s T-DM1 but will use it as approved, not earlier off-label. ♦ It’s too early to predict how Pfizer’s PF-05280014, a biosimilar Herceptin (trastuzumab), will do but pricing will be important.  Celldex’s glembatumumab vedotin (CDX-011), a tubulin inhibitor, appears to work in a subset of triple-negative breast cancer patients. ♦ PI3K inhibitors continue to look promising in metastatic breast cancer, particularly Novartis’ buparlisib (BKM- 120) and perhaps Novartis’ BYL-719. ♦ Medivation and Astellas’ Xtandi, a prostate cancer drug, may have utility in Doctors are anxious for FDA approval of Roche/Genentech’s T-DM1 but will use it as approved, not earlier off-label. ♦ It’s too early to predict how Pfizer’s PF-05280014, a biosimilar Herceptin (trastuzumab), will do but pricing will be important. ♦ Celldex’s glembatumumab vedotin (CDX-011), a tubulin inhibitor, appears to work in a subset of triple-negative breast cancer patients.  PI3K inhibitors continue to look promising in metastatic breast cancer, particularly Novartis’ buparlisib (BKM- 120) and perhaps Novartis’ BYL-719. ♦ Medivation and Astellas’ Xtandi, a prostate cancer drug, may have utility in

CMS’ MEDCAC Considers VAD Coverage Issues

 The Centers for Medicare and Medicaid Services (CMS) Office of Clinical Standards and Quality, Coverage and Analysis Group, Division of Medical and Surgical Services, asked a Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) to discuss Medicare’s existing national coverage determination (NCD) for ventricular assist devices (VADs), focusing on how to select appropriate patients and centers as well as who may do the procedures.

FDA Advisory Committee Recommends Approval of Aegerion’s Lomitapide for HoFH

Despite concerns about toxicity and possible liver damage, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-2 to recommend approval of Aegerion Pharmaceuticals’ lomitapide for the treatment of homozygous familial hypercholesterolemia (HoFH), saying it was clear that the drug works to lower LDL.

Transcatheter Cardiovascular Therapeutics (TCT): Stem Cells

There was no real news at TCT on stem cells. Experts still believe they will eventually succeed, at least in heart failure, but are perhaps a decade or more away from real clinical utility. ♦ There are still many unanswered questions – from what type of cells to what conditions to treat, trial design, patient enrollment, etc. ♦ The most promising approaches right now appear to be Baxter’s CD34 cells and Cytori Therapeutics’ Celution, but there is a long list of companies trying to find a solution that works.

TRANSCATHETER CARDIOVASCULAR THERAPEUTICS (TCT): STEM CELLS

There was no real news at TCT on stem cells. Experts still believe they will eventually succeed, at least in heart failure, but are perhaps a decade or more away from real clinical utility. ♦ There are still many unanswered questions – from what type of cells to what conditions to treat, trial design, patient enrollment, etc. ♦ The most promising approaches right now appear to be Baxter’s CD34 cells and Cytori Therapeutics’ Celution, but there is a long list of companies trying to find a solution that works.

American Neurological Association

LILLY’s solanezumab failed in Alzheimer’s disease, but experts still hold out hope for the beta-amyloid theory and perhaps solanezumab – with more studies. ♦ Tau aggregation inhibitors are another option, though experts did not appear really excited about them. ♦ An NIH study found there is no safe level of JC virus in the CSF. ♦ Neurologists treating multiple sclerosis said they plan to prescribe Sanofi/Genzyme’s Aubagio, but they predicted Biogen Idec’s BG-12 will be the No. 1 oral agent when it is approved. ♦ There continues to be little interest in Questcor Pharmaceuticals’ Acthar injectable gel for MS flares. ♦ A Phase I trial showed very positive results with Alexion Pharmaceuticals’ Soliris (eculizumab) in preventing flares in patients with neuromyelitis optica.

American Neurological Association

LILLY’s solanezumab failed in Alzheimer’s disease, but experts still hold out hope for the beta-amyloid theory and perhaps solanezumab – with more studies. ♦ Tau aggregation inhibitors are another option, though experts did not appear really excited about them. ♦ An NIH study found there is no safe level of JC virus in the CSF.  Neurologists treating multiple sclerosis said they plan to prescribe Sanofi/Genzyme’s Aubagio, but they predicted Biogen Idec’s BG-12 will be the No. 1 oral agent when it is approved. ♦ There continues to be little interest in Questcor Pharmaceuticals’ Acthar injectable gel for MS flares. ♦ A Phase I trial showed very positive results with Alexion Pharmaceuticals’ Soliris (eculizumab) in preventing flares in patients with neuromyelitis optica.

26th Annual North American Cystic Fibrosis Conference (NACFC)

Vertex Pharmaceuticals’ combination of lumicaftor (VX-809) and ivacaftor (Kalydeco, VX-770) in homozygous F508del mutation patients missed the primary endpoint (sweat chloride), but experts focused instead on the improvement in FEV1, which they said was more important clinically and justifies a Phase III trial. The combination of VX-809 and VX-770 did not work at all in heterozygous F508del patients. ♦ The uptake of Vertex’s Kalydeco has been nearly 100%, but there is almost no off-label use because of the cost. So far, doctors are pleased with the clinical results. If Kalydeco proves beneficial in other rare non-gating mutations, doctors will try to use it off-label, but only if insurance will pay for it. ♦ Medicaid and private insurance have been covering Kalydeco, but some carriers (particularly Medicaid) are requiring demonstrated benefit to continue treatment. Experts are worried that expanding treatment to more CF patients with expensive drugs like Kalydeco will put CF on the radar screen and potentially make coverage more challenging.

26th Annual North American Cystic Fibrosis Conference (NACFC)

Vertex Pharmaceuticals’ combination of lumicaftor (VX-809) and ivacaftor (Kalydeco, VX-770) in homozygous F508del mutation patients missed the primary endpoint (sweat chloride), but experts focused instead on the improvement in FEV1, which they said was more important clinically and justifies a Phase III trial. The combination of VX-809 and VX-770 did not work at all in heterozygous F508del patients. ♦ The uptake of Vertex’s Kalydeco has been nearly 100%, but there is almost no off-label use because of the cost. So far, doctors are pleased with the clinical results. If Kalydeco proves beneficial in other rare non-gating mutations, doctors will try to use it off-label, but only if insurance will pay for it. ♦ Medicaid and private insurance have been covering Kalydeco, but some carriers (particularly Medicaid) are requiring demonstrated benefit to continue treatment. Experts are worried that expanding treatment to more CF patients with expensive drugs like Kalydeco will put CF on the radar screen and potentially make coverage more challenging.

European Society of Cardiology: Drugs

Oral anticoagulants Use growing slowly, may reach 50% in 5 years ♦ Factor Xa antidote Portola PRT-064445 early, exciting, but maybe more a comfort than use ♦ Antiplatelet agents Lilly’s Effient no better than clopidogrel ♦ OTC statins Cardiologists do not favor, worry about monitoring s CETP inhibitors Doctors cautious about outlook to raise HDL ♦ Familial hypercholesterolemia Niche market but room for several new drugs at the same time ♦ Omega-3 fatty acids Doctors more leery, which doesn’t bode well for Amarin’s Vascepa

European Society of Cardiology: Drugs

Oral anticoagulants Use growing slowly, may reach 50% in 5 years. ♦ Factor Xa antidote Portola PRT-064445 early, exciting, but maybe more a comfort than use. Antiplatelet agents Lilly’s Effient no better than clopidogrel. OTC statins Cardiologists do not favor, worry about monitoring. CETP inhibitors  Doctors cautious about outlook to raise HDL. Familial hypercholesterolemia Niche market but room for several new drugs at the same time. Omega-3 fatty acids Doctors more leery, which doesn’t bode well for Amarin’s Vascepa

European Federation of Neurological Societies (EFNS)

Alzheimer’s disease experts are not giving up on anti-amyloid-beta antibodies, despite the “disappointing” news on Johnson & Johnson and Pfizer’s bapineuzumab and Lilly’s solanezumab. Roche’s gantenerumab now has the lead. ♦ The details on bapineuzumab offered little hope for that drug. There wasn’t even a hint of efficacy, though researchers tried to find hope in some hints of phospho-tau effect in the CSF. ♦ There was no enthusiasm at the meeting for oral BACE inhibitors for AD. ♦ There were no important data on new multiple sclerosis drugs at EFNS, just incremental supportive data. ♦ Switching among MS drugs is likely to become even faster with the new drugs coming. ♦ A possible biomarker for responders to Biogen Idec’s daclizumab was identified, and high levels of IL-7 and IL-21 may predict who will develop serious side effects with Sanofi/Genzyme’s Lemtrada (alemtuzumab). ♦ The FDA’s rejection of Lemtrada was blamed entirely on “technical issues” with the data format. No new filing date was suggested.

FDA Approves Gilead’s Truvada For HIV Prevention

The FDA approved a supplemental new drug application (sNDA) for Gilead Sciences’ Truvada (emtricitabine + tenofovir) for HIV prevention (PrEP). It was already approved – and so were the individual components – to treat HIV. This is the first FDA-approved medication that reduces the risk of sexual transmission of the HIV virus – helping to prevent a non-infected person from contracting HIV through sex with an HIV-infected person.

FDA Advisory Committee Recommends Approval of Edwards’ Sapien Valve for Some Operable Patients

The FDA’s Circulatory System Devices Advisory Committee voted overwhelmingly to recommend that the label for Edwards Lifesciences’ Sapien transcatheter aortic valve replacement (TAVR) system be expanded to include operable patients who have ≥15% risk of mortality for open heart aortic (surgical) valve replacement (AVR). Sapien was already approved for inoperable patients. The panel voted 10-2 that the valve is safe, 12-0 that it is effective, and 11-0 (with 1 abstention) that the benefits outweigh the risks.

FDA Advisory Committee Recommends Approval OF Gilead Sciences’ 4-in-1 HIV PILL

The FDA’s Antiviral Drugs Advisory Committee voted 13-1 to recommend approval of Gilead Sciences’ Quad (elvitegravir + cobicistat + emtricitabine + tenofovir disoproxil fumarate), a fixed-dose combination (EVG/COBI/FTC/TDF) for adults with HIV-1 infection who are treatment-naïve or have no known substitutions associated with resistance to the individual components. If approved, Quad would be the third single-pill, once-daily complete regimen for HIV, along with Gilead’s Atripla (efavirenz, emtricitabine, tenofovir) and Complera (rilpivirine, emtricitabine, tenofovir). Gilead makes all four drugs in the Quad pill.

American Academy of Dermatology (AAD)

The economy appears to be picking up, just a little, and dermatologists are considering big ticket purchases again, but cautiously.  Most aesthetic procedures – fillers, toxins, and laser treatments – are flat compared to this time last year.  Allergan’s Botox remains the top toxin choice of doctors and patients. Merz’s Xeomin may be more of a challenger, though, than Medicis’ Dysport, and Revance’s topical toxin could be a game-changer.  Valeant hopes to build on its purchase of Dermik and build a strong aesthetics business. Watch for more acquisitions.  Copay discount/rebate cards help encourage brand product use, but some pharmacists make use difficult.  The new psoriasis therapies in development are still too far away to generate much enthusiasm among most dermatologists. ? Acne medications are little differentiated, with choice often due to habit.

FDA Advisory Committee Recommends Cardiovascular Safety Trials for All Obesity Drugs

 The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee met for two days, tasked by the FDA with providing guidance on what parameters the FDA should set for the analysis of cardiovascular (CV) safety in trials of obesity drugs, and decided 17-6 that basically all obesity drugs should have cardiovascular outcomes trials, usually before approval, often with an additional study post-approval.

Conference on Retroviruses and Opportunistic Infections (CROI)

Experts actually believe a cure for HIV may be possible. In the meantime an HIV vaccine is looking more likely, but experts are convinced it needs to be a broadly neutralizing antibody.  Gilead Sciences’ Quad showed noninferiority to Atripla, with fewer CNS side effects but more nausea, and doctors expect it to be approved by the FDA. Within a year, they predicted 54% of their naïve HIV patients will go on it, with 15% of patients switching from Atripla or another regimen.  Gilead’s GS-7340 looks like a promising new tenofovir that would be better for combinations, but doctors want a lot more data on it first. ? ViiV’s dolutegravir appears to be the best integrase inhibitor yet, and ViiV plans a triplet pill, Trii, to compete with Quad.  Gilead’s PSI-7977 failed spectacularly in HCV-1 null responders, but longer therapy or the addition of an NS5A may solve the problem.  Both Merck’s Victrelis and Vertex’s Incivek work about as well in HIV/HCV coinfected patients as they do in HCV alone, but reimbursement is a big issue, though guideline changes could help that.  Despite mixed signals from various international trials, drugs to prevent HIV appear close to approval, starting with Gilead’s Truvada, which goes before an FDA advisory committee on May 10, 2012.

FDA 2012 Genitourinary Cancers Symposium

Use of Dendreon’s Provenge appears to have plateaued at existing sites, though new sites continue to initiate use.  BothMedivation’s MDV-3100 and Bayer’s Alpharadin showed a significant survival benefit in CRPC. ? Doctors are happy to have multiple prostate cancer agents but struggle with how to sequence them.  Lilly – but perhaps not ImClone – may have given up onramucirumab in prostate cancer.  Two different approaches to mCRPC – Merck KGaA’s EMD-525797 and OncoGenex Pharmaceuticals’ OGX-427 – both bear watching.  In renal cell carcinoma, keep an eye on Argos Therapeutics’ AGS-003 and Aveo Pharmaceuticals and Astellas Pharma’s tivozanib, though AGS-003 could have a pricing issue and tivozanib may have some QT issues.

American Academy of Pain Medicine (AAPM)

The focus of AAPM this year was not on new pain drugs in development but on the state of the profession amidst the continuing struggle between providing appropriate pain relief and opiate abuse. Just a few years ago, the list of new pain medications in the pipeline was so long, it took a chart to keep track of all of them. Now, there are very few, and pain medicine doctors appear to have little appetite for newer agents. Probably the most exciting new research is with agents targeting glial cells.

2012 Gastrointestinal Cancers Symposium

Novartis’ Afinitor had mixed results – positive news in a reanalysis in neuroendocrine tumors (NET) and negative news in gastric cancer.  Bayer’s regorafenib showed a statistically significant benefit vs. placebo in survival in CRC. Though it was just a 1.4 month improvement, most experts predicted the FDA will approve it.  Bristol-Myers Squibb’s brivanib failed in CRC, but experts are still hopeful it will be beneficial in HCC.  Bayer’s Nexavar showed a very small but statistically significant improvement in a Phase II trial in HCC, but experts were not convinced of the value, given the toxicity.  Exelixis’ cabozantinib showed positive data in a Phase II trial in HCC whether or not patients were pretreated with Bayer’s Nexavar.  Experts see little difference among the various somatostatin analogs.  A study found Genomic Health’s Oncotype DX Colon assay caused doctors to change treatment decisions 29% of the time.  Genta is developing an oral taxane that is worth watching.

Transcatheter Cardiovascular Therapeutics (TCT)

Commercial uptake of Edwards Lifesciences’ Sapien may be slower than some projections because hospitals initially will lose money on procedures and patients may be enrolled in clinical trials instead. Sites may do an average of <5 commercial procedures a month.  ♦ The Danish STACCATO trial raised questions about the safety of the transapical approach to TAVR, but most cardiologists and surgeons remain convinced of the value of TA.  ♦ Cardiologists continue to take a cautious view of Abbott’s MitraClip for mitral valve repair, wanting more trial data.  ♦ The FDA is investigating longitudinal DES compression, which appears worse with Boston Scientific and Medtronic stents, but cardiologists believe it is a rare event and are not abandoning either Medtronic or Boston Scientific stents.  ♦ The conclusion was that Accumetrics’ VerifyNow is great for research but not useful for individual patients.  ♦ Renal denervation was described as potentially “transformational.” Medtronic has the lead, but other companies aren’t far behind. The FDA is concerned about safety and durability and cautioned that doctors can’t use just any off-the-shelf catheter for this.

American Hear Association (AHA) Scientific Sessions 2011

Antiarrhythmic drugs – Increasing concern over safety of Sanofi’s Multaq, as potential competitors flounder. ♦ Anticoagulation – In ACS, a win for Johnson & Johnson’s Xarelto but not Merck’s vorapaxar. In VTE, BMS’ Eliquis failed to beat Sanofi’s Lovenox. ♦ Diabetes drugs and the heart – The jury is still out. ♦ Lipid lowering agents – AstraZeneca’s Crestor no better but no worse than Pfizer’s Lipitor (or generic atorvastatin), Abbott’s Niaspan use likely to continue to decline, and CETP inhibitors still alive. ♦ Omega-3 fish oils – Not generating any excitement among cardiologists.

Transcatheter Cardiovascular Therapeutics (TCT)

Commercial uptake of Edwards Lifesciences’ Sapien may be slower than some projections because hospitals initially will lose money on procedures and patients may be enrolled in clinical trials instead. Sites may do an average of <5 commercial procedures a month. ♦ The Danish STACCATO trial raised questions about the safety of the transapical approach to TAVR, but most cardiologists and surgeons remain convinced of the value of TA. ♦ Cardiologists continue to take a cautious view of Abbott’s MitraClip for mitral valve repair, wanting more trial data. ♦ The FDA is investigating longitudinal DES compression, which appears worse with Boston Scientific and Medtronic stents, but cardiologists believe it is a rare event and are not abandoning either Medtronic or Boston Scientific stents. ♦ The conclusion was that Accumetrics’ VerifyNow is great for research but not useful for individual patients. ♦ Renal denervation was described as potentially “transformational.” Medtronic has the lead, but other companies aren’t far behind. The FDA is concerned about safety and durability and cautioned that doctors can’t use just any off-the-shelf catheter for this. 

Radiological Society of North America (RSNA)

Our coverage of RSNA was limited this year because of a schedule conflict, so we focused on two main areas: the general capital spending environment for imaging and the outlook for 3D mammography (or tomosynthesis). Fourteen radiologists were interviewed. Overall, they said budgets are flat to down, and most purchases, if any, are replacements or upgrades.

FDA Advisory Committee Rejects CardioMEMS' Champion Heart Failure Monitoring System

The FDA’s Circulatory System Devices Advisory Committee recommended against approval of CardioMEMS’ Champion heart failure monitoring system, an implantable wireless device that measures pulmonary artery (PA) pressure in patients who have been hospitalized with New York Heart Association (NYHA) Class III heart failure (HF). The permanent device has a battery-free capacitive pressure sensor/monitor implanted in the pulmonary artery, a transvenous catheter delivery system, and an electronics system to receive the data and put it in a database for review.

FDA's Advisory Committee Approves Retreatment Trial Design for Salix's Xifaxan in IBS-D

The FDA’s Gastrointestinal Drugs Advisory Committee gave the green light to Salix Pharmaceuticals’ proposal for a retreatment trial for Xifaxan (rifaximin) in patients with irritable bowel syndrome with diarrhea (IBS-D), despite concerns about the trial design, the drug’s efficacy, and the unknown mechanism of action. Xifaxan already is approved for treatment of hepatic encephalopathy and travelers’ diarrhea. It would be the first antibiotic approved for IBS-D patients.

European Society of Cardiology (ESC)

Bristol-Myers Squibb/Pfizer’s Eliquis (apixaban) was the talk of the meeting, and the data looked very good, but doctors warned not to count Boehringer Ingelheim’s Pradaxa and, especially, Johnson & Johnson/ Bayer’s Xarelto out yet, and they still see a large role for warfarin for at least the next 5-10 years. Despite only preclinical data, there was great optimism about Portola’s PRT-064445 antidote for Factor Xa inhibitors.  CETP inhibitors are alive, but cardiologists are reserving judgment until there are more data.  Omega-3 fish oils – Abbott’s Omacor and Amarin’s AMR-101 – got a push at ESC, but doctors had little interest, and the differences appeared more marketing messages than real.  Platelet reactivity testing, particularly Accumetrics’ VerifyNow point-ofcare test, is growing but slowly.  Use of Abbott’s MitraClip for mitral valve repair is growing but the learning curve, difficulty, and patient selection remain issues. FDA approval is uncertain, and if it is approved, it is still likely to be a relatively niche product.  Early data on longer term durability of percutaneous aortic valves looks good.

FDA’S Advisory Committee Recommends Tougher Approval Path for Transvaginal Surgical Mesh

The FDA’s Obstetrics and Gynecology Devices Advisory Committee met for two days to consider the safety and efficacy of transvaginal surgical mesh used for repair of pelvic organ prolapse (POP) and for stress urinary incontinence (SUI). The panel was convened because of continued concern about adverse events, including vaginal erosion that led to pelvic pain and dyspareunia.

American Academy of Family Physicians (AAFP)

Cost-consciousness up. Cutting costs is of paramount importance to doctors, hospitals, insurers, and patients, so generic drugs are prescribed whenever possible. ♦ E-prescribing conversion slow. Few practices have fully implemented e-prescribing, although most said it will be done in the next 12-18 months. ♦ Slow adoption of new drugs: Family doctors are not very interested in expensive new options like (1) Boehringer Ingelheim’s Pradaxa for atrial fibrillation which is expensive and has a narrow indication. (2) Merck’s Januvia and Janumet for Type 2 diabetes, where use is low, but Bristol- Myers Squibb’s Onglyza is starting to catch on, though Boehringer Ingelheim’s Tradjenta is not on the radar yet. Metformin and, surprisingly, insulin are preferred. (3) GLP-1s, which are expensive and injected, though Lilly/Amylin’s weekly Bydureon could expand use. ♦ Cholesterol focus on generics and OTC. Generic simvastatin is inexpensive, so there is little interest in generic atorvastatin because it is likely to cost more. Family doctors recommend omega-3 fatty acids, but over-the-counter supplements, not prescription products.

FDA Advisory Committee Rejects Bristol-Myers Squibb and AstraZeneca’s Diabetes Drug, Dapagliflozin

FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted against approval of Bristol-Myers Squibb (BMS) and AstraZeneca’s dapagliflozin, a first-in-class sodium glucose cotransporter-2 (SGLT-2) inhibitor “as an adjunct to diet and exercise to improve glycemic control in patients with Type 2 diabetes when used as either monotherapy or an add-on to other oral antidiabetic agents or added to insulin.” The panel rejected dapagliflozin by a vote of 9 to 6, citing concerns about data, long-term effects of the drug, efficacy (particularly in renally impaired patients), and safety, especially breast and bladder cancer and hepatic toxicity.

European League Against Rheumatism (EULAR)

Use of Human Genome Sciences and GSK’s Benlysta for lupus varies widely, from none at some academic centers to nearly 100% in some private practices with an infusion center. The spoiler may be Immunomedics/ UCB Pharma’s epratuzumab, which could have better efficacy and dosing, and J&J’s sirukumab is far away but subcutaneous. ♦ The market for approved rheumatoid arthritis (RA) drugs is pretty stable, with little payor pressure to use specific biologics. Bristol-Myers Squibb’s Orencia, J&J’s Simponi, and Roche’s Actemra are not picking up much market share. ♦ New oral RA drugs will be used ahead of TNF inhibitors – if they are safe. Pfizer’s tofacitinib continues to show remarkable efficacy, and Pfizer is beginning to address the safety issues, but questions remain. Rigel and AstraZeneca’s fostamatinib looks efficacious and safer than tofacitinib, but patients may not feel as good on it. Lilly’s oral BAFF inhibitor LY-2127399 showed somewhat spotty efficacy, but safety was pretty good, except for some infections. Watch Galapagos’ JAK1 inhibitor. ♦ Doctors are dubious about Crescendo Bioscience’s Vectra DA biomarker blood test for RA. Doctors are enthusiastic about all of the new gout drugs – including Ardea’s lesinurad and Regeneron’s Arcalyst – except that cost may limit use.

American Psychiatric Association (APA)

A brief review of the APA meeting, with some perspective on what was hot at the meeting and what was not with respect to newly approved or investigational psychiatric drugs, courtesy of some doctor friends attending the meeting.

American Pain Society (APS)

Experts predicted that both opioid use and opioid doses will decline due to the FDA’s new opioid REMS.  A number of new medications are in development to treat opioid-induced constipation. Salix’s injectable Relistor is being reserved for very refractory patients.  About 20% of APS members use Suboxone off-label for pain, and use would increase even more if there were an FDA-approved sublingual buprenorphine for pain.  AcelRx’s ARX-01, a sufentanil for postop hospital use, looks very interesting, but ARX-03 for officebased procedures was less impressive.  Industry is still interested in nerve growth factors, and researchers were defending their safety, but the future of the class remains in jeopardy

American College of Cardiology (ACC)

ACC wasn’t as exciting this year as in many years past, and the key trials reported mixed results: ♦ Edwards Lifesciences’ Sapien percutaneous aortic valve beat surgery in the PARTNER Cohort A trial. ♦ Abbott’s MitraClip for percutaneous mitral valve repair was safe and effective in high-risk patients in the EVEREST-II trial. ♦ New coronary stents – Abbott’s Absorb, Boston Scientific’s Promus Element, and Medtronic’s Resolute – all had good data, but the stent market has matured, and now everyone is vying for a larger piece of a non-expanding pie. ♦ Radial access for coronary interventions (stents) did not beat femoral access in the RIVAL trial, but use of radial access is expected to increase. ♦ Abiomed’s Impella failed to beat IABP in the PROTECT-II trial. ♦ Bayer and Johnson & Johnson’s Xarelto showed a negative net clinical benefit in VTE prevention, and the hepatic profile warrants further investigation.

18th Conference on Retroviruses and Opportunistic Infections (CROI)

Doctors were very interested in Bristol-Myers Squibb’s attachment inhibitor BMS-663068 and GSK’s oncedaily integrase inhibitor dolutegravir (GSK-1349572).  Yet, the real excitement at CROI was over zinc finger technology developed by Sangamo Biosciences that can be used in several different ways to disable the CCR5 and CXCR4 cells that HIV depends on to survive.  Once-daily oral regimens are extremely important in HIV, but doctors are not ready to jump quickly to new QD regimens like Gilead’s Btripla or Quad, which are likely to be reserved for patients who cannot/will not take Gilead’s Atripla.  Gilead’s Viread (tenofovir) has an important role in both HIV and hepatitis B, but a new low-dose, high potency prodrug, GS-7340, could replace it for many uses, except perhaps prevention.  Merck’s Isentress (raltegravir) continues to have a loyal following despite its BID dosing because of good tolerability.  Both Merck’s Victrelis (boceprevir) and Vertex’s telaprevir appear to be effective in HIV/HCV co-infected patients.

Cardiovascular Research Technologies (CRT) Conference

Edwards Lifesciences’ Sapien transcatheter aortic valve is expected to beat surgery in the PARTNER Cohort A and to get accelerated approval from the FDA.  U.S. reimbursement for TAVI is still uncertain, and cardiologists are more worried about escalating healthcare costs. CMS does not appear to have a reimbursement plan in mind yet.  The idea of limiting TAVI to “centers of excellence” appears to have been abandoned, but experts agree that not every hospital should be doing the procedure, emphasizing the need for training and a team approach.  Many cardiologists want to use TAVI offlabel in lower-risk patients, and the FDA seems to accept that this will happen, but doctors are approaching this cautiously.  Interest is growing in embolic protection with TAVI to lower the stroke rate.  Second-generation TAVI devices may offer repositioning and retrievability, which are viewed as important features.  Although FDA requirements for TAVI device approval continue to be criticized as hindering innovation, the Agency is not lowering the bar.  FDA is expected to mandate TAVI training but leave the details to industry.

American Society of Clinical Oncology's Genitourinary Cancers Symposium (ASCO-GU)

A study found that prostatectomies with Intuitive Surgical’s da Vinci robot should be restricted to high volume doctors/centers. ♦ Demand for immunotherapy with Dendreon’s Provenge is expected to increase – and treatment delays shrink – as new plants come on line. ♦ Medical oncologists are very excited about Exelixis’s cabozantinib (XL-184) because of its “dramatic” effect on bone mets and pain, but toxicity is a concern. ♦ OncoGenex/Teva’s custirsen may be the dark horse, with low awareness but very good Phase II results that need confirmation from an ongoing Phase III trial. ♦ Doctors are anxious to use Johnson & Johnson’s abiraterone and/or Medivation/Teva’s MDV-3100 – and to use them pre-chemotherapy – but they haven’t figured out how to sequence them with Provenge yet. ♦ Doctors are not enthusiastic about Amgen’s Xgeva, sticking with Novartis’s Zometa, though Xgeva may slowly gain usage.

Angiogenesis, Exudation, and Degeneration 2011

Roche/Genentech’s Avastin has 60% of the VEGF market for wet AMD vs. 40% for Lucentis, and the CATT trial is unlikely to change this unless the results are unexpectedly dramatic.  New Phase III data in wet AMD for Regeneron’s aflibercept (VEGF Trap-Eye) looked very good, showing non-inferiority to Lucentis with all dosing regimens, including Q8W, and 43% of doctors said Trap would be their preferred anti-VEGF if Medicare pays for it and the cost is less than or equal to Lucentis. It is also likely to be used in Avastin/Lucentis failures.  No Medicare national coverage decision on VEGF drugs is expected unless someone requests one for aflibercept, in which case CMS would review all three VEGF inhibitors.  Glaucoma is an increasingly common side effect of anti-VEGF therapy and appears related to the number of injections.  Ophthotech has three drugs for AMD that look interesting. Radiation therapies are getting a watchful eye but not much enthusiasm, and the regulatory outlook is questionable. Doctors also aren’t very enthusiastic about Alimera Sciences’ Iluvien fluocinolone implant for DME.