Weekly Roundup 9.30.16

The shifting of gears is happening before our eyes. Already leaves are falling and the morning alarm goes off in the final moments of night time darkness rather than the first rays of morning sunshine. The trees are signalling that they are ready for their slumber. I have been too – away on a Equinox vacation. I’m back, so let’s see what happened not just over the past week, but two.

Or first, what didn’t happen. There were no new OPDP action letters posted these past few weeks, but we are now up to four for what is shaping up to be a new low in the number of enforcement letters posted by the office.

But a few things did happen and here are some that I wanted to highlight:

  • FDA Approves First Drug to Treat Duchenne’s Muscular Dystrophy – It was perhaps one of the more anticipated decisions by FDA on a product this year. That was because it treats a rare, yet devastating condition in children where there were no options. And it was because the clinical trial was small. And because these and other factors would cause FDA to step outside of its usual approach in considering new approvals. Amid media reports of internal dissension within the agency, and after some delay, FDA ultimately announced approval of Exondys 51 for the treatment of a subset of people with Duchenne’s Muscular Dystrophy (DMD) who have a specific gene mutation (about 13 percent of the DMD population).  The compound had fast track, orphan drug and priority review designation. The company stated in its release on the approval that a clinical benefit has not yet been established for the treatment and that continued approval may be contingent upon seeing that benefit in future confirmatory trials.
  • Automated Insulin Delivery Device Approved - Hailed as the first “artificial pancreas”, FDA this week announced that it was giving the ok to the first device designed to do what the pancreas does – to deliver insulin to the body on a regular basis. The device, the MiniMed 670G hybrid closed loop system, is equipped with a sensor to monitor glucose levels and deliver insulin through an infusion patch connected to an insulin pump, worn externally. The device was studied in a trial consisting of 123 people. The indication is in patients 14 years and older with Type 1 diabetes and the agency will be looking for a post-market study to get a clearer picture on actual use in the real world. Details and photos on the use and range of the device can be found on the company site. The company says the new system will be ready for shipping in Spring, 2017.
  • The “Close-Hold Embargo” and FDA – Anyone working in media is familiar with a news embargo. It allows an entity with news to share it with reporters prior to an official announcement so that stories can be ready for publication when the news actually happens. It is a handy tool for both sides. Add the words “close-hold” prior to the word embargo, however, and you have controversy.  That is what happened with the publication of an article detailing a practice at FDA known as the “close-hold embargo” whereby the news was not only embargoed, but the ability for a reporter to talk to others to get input and point of view to help shape the story was also proscribed. The idea that a federal agency would tell reporters who to report the news – or to intervene in the reporting process brought to light by the article, generated a good deal of critical comment during the course of the week. Agree with it or not, it may not be perceived as bolstering the notion of transparency.

That’s it for me this week. Have a good weekend everyone. Happy Autumn!

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Breakthrough Therapy Status, AdComms and Approvals

In recent years FDA has undertaken several means to facilitate the consideration of new drug applications by creating various mechanisms for expedited review for either new drugs or new indications for existing drugs. Prior to 2012, there had long been in place Accelerated Approval and Fast Track and Priority Review. In 2012, as a consequence of the enactment of the Food and Drug Administration Safety and Innovation Act (FDASIA), Breakthrough Therapy (BT) status was added as a means to gain speedier consideration of new drugs that would make an impact in the treatment environment.

All of the expedited means have had impact. In fact, by 2015, which was a banner year for the approval of new molecular entities, fully half of them had had some form of expedited review.

Breakthrough Therapy designation has been increasingly common since 2013 when there were a handful of drugs granted the status. In 2014, the number increased dramatically. By the end of the first quarter of this year, FDA has stated that it has granted breakthrough status to 111 out of 342 requests. FDA does not announce the status outcomes for specific companies.

What exactly does Breakthrough Therapy mean and what does FDA do with it?  The agency has said that the purpose is to indicate early in the drug development process that a compound has the potential to represent a true breakthrough in the long run. That, in turn, means that the agency will invest a number of resources to see that the compound gets evaluated in a highly efficient manner with regular input and advice from key FDA personnel. Receiving Breakthrough Therapy status means that the drug is treating a serious condition and that there is an indication of a potential to be a substantial improvement over existing treatments.

While the agency does not announce the designations when they occur, FDA does list the approvals that have occurred for compounds that have been designated as a Breakthrough Therapy. When you look at the list of drugs and biologics breakthrough therapies that have been approved and compare it to the list of drugs and biologics that have had advisory committee meetings in the course of their approval process reveals a surprising number.

Per the CDER list of Breakthrough Therapy approvals by calendar year – here and here, there have been 44 BT approvals as of June 30 of this year. However, FDA advisory committees have met only four times to consider investigative compounds for approval that have had breakthrough status. The balance – and bulk – of compounds that have had Breakthrough Therapy status were approved without an advisory committee meeting.

Does that mean that breakthrough status is a sort of surrogate marker for drugs that will not require an AdComm?  Probably not, but it does perhaps say that the process that is signified by breakthrough status – of working closely with FDA regarding key issues in the drug approval process – may for the most part make an advisory committee meeting less necessary under most circumstances. That said, there will still be circumstances where the agency would appear to believe that it still needs the input of advisory committee members in considering the drug application.

I was able to identify four instances in which there was an advisory committee meeting where a breakthrough status compound was the subject of approval deliberations.  In all four of these meetings the committees all voted to approve and FDA took the advice of the committee and ultimately approved all four.

For more on Breakthrough Therapy status, you can read an FDA Q&A here, a Fact Sheet here, and an informative interview here.

No Weekly Roundup today – but back next week.

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Posted in Advisory Committee Prepapartion, FDA Policy | 1 Comment

Weekly Roundup 9.16.16

Kids are back in school. The air is kinder, gentler and less harsh than the last heated days of summer, though summer tries to hang on some days, it is ebbing into Autumn. Halloween candy has already appeared in stores.

There was no Weekly Roundup last week, so some of what is included this week laps over. Here is a bit of what happened while we transition the season.

  • OPDP Sends Out Letters! – After a long period of lethargy on the enforcement front, in the past few weeks FDA has sent out 2 enforcement letters which literally doubles the number sent so far this year. Between the two, an op-ed I wrote for The Hill appeared about the lack of enforcement – timing is everything. Interestingly the two letters involved the same basic violation – the promotion of a compound prior to approval – which on the whole has been one of the rarer violations cited by OPDP over the years (the leading being, of course, the lack or minimization of risk information). Does this thaw mean that OPDP is returning to enforcement activities or is it merely an anomaly. I think probably the latter, but time will tell. Note that one of the letters was issued in August, and one in September, but posting of the letters is not immediate.
  • FDA Blog Post About Access and Pricing - In the wake of the recent pricing action around Epi-Pen and the accompanying media and policy-maker attention to the issue of pricing as a result, FDA’s Dr. Janet Woodcock, head of CDER, authored a posting on the agency’s FDA Voice blog called “FDA and Access to Medications”. In it, she explains that while many people look to the agency around pricing matters, the agency does not have anything to do with pricing, but rather its role is confined to assessing the safety and efficacy of products. In response to some of the concerns raised about FDA’s pace at considering generics for approval, she stated that the agency stands ready to consider applications for generic products and puts the first of such applications in a category on a priority.
  • FDA AdComm Recos Removal of Boxed Warning – A joint meeting of the Drug Safety and Risk Management and the Psychopharmacologic Drugs Advisory Committees resulted in a majority vote recommending removal of a boxed warning that exists for smoking cessation product Chantix. The committee reviewed data from a study – Evaluating Adverse Events in a Global Smoking Cessation Study – EAGLES – that looked at safety issues associated with use of the product which had a boxed warning regarding neuropsychiatric events in patients, which the company says will be retained in the Warnings and Precautions section of the labeling. FDA may or may not follow the recommendation of its advisory committee

That’s all for this week. Have a good weekend everyone. Next week – a look at Breakthrough Therapy Designation.

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Weekly Roundup 9-2-16

The end of summer.

This is less like a Weekly Roundup than a Monthly Roundup. Like everyone else, I have taken August with a grain of salt. It feels a little lonely writing blog postings when you know that readers have headed out to beaches and mountains and are getting much deserved rest and relaxation. So I got a little in too.

Still, things happened, and here we are at the cusp of the Labor Day Weekend when we slip out of summer and for this year – fully into the election cycle. So here are a few of the interesting items of note.

  • FDA Ups the Warnings on Opioids – The agency announced class-wide changes to safety requirements for prescription opioid analgesics, cough medicines containing opioids, and benzodiazapines – both classes of drugs that are central nervous system depressants – to warn that combined use of these products pose serious risk, including extreme sleepiness, respiratory depression, coma and death. The new measures will include a boxed warning on products (over 400 by FDA’s count) as well as Medication Guides. FDA said that the announced label changes were part of its ongoing Opioids Action Plan.
  • FDA Revises Recommendation on Zika Blood Screening – In February FDA issued curious guidance recommending that only blood and blood products collected in geographical areas where there is an active Zika outbreak be screened for Zika. This week the inevitable occurred with the agency announcing a revision of the earlier guidance to include all blood and blood products in the United States for purposes of screening.
  • FDA to Hold Public Discussion About Unapproved Use Communications - The agency announced this week that it would be holding a two-day public meeting to get input on the subject communication by manufacturers of unapproved uses for drugs, biologics and devices. The meeting will be held November 9 and 10 and those wishing to provide comment at the meeting are directed by FDA to register by October 19 with electronic comments being accepted until January 9, 2017. The meeting will be held at the FDA facility in Silver Spring. More information can be found in the Federal Register announcement located here.

That’s it for me this week folks. I hope you had a good summer. Time to get out the books and get back to work. I’ll do that next week. Have a wonderful weekend.

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This is Your State, This is Your State on Drugs

I always enjoy doing a periodic check in on what states are doing when it comes to healthcare issues. Utilizing the excellent data base resources at the National Conference of State Legislatures, one can examine numerous categories of legislation that is being considered before the 50 states and the District of Columbia.

The last check in was in February and provided a general overview of health related legislation, including biosimilars, prescription drug abuse and pricing. But as prescription drug pricing has been one of the issues that has risen to the top when it comes to the national election cycle, that is the specific focus of the day.

When we last checked in six months ago, there were 160 bills related to pharmaceutical pricing in 30 states. Pharmaceutical pricing is a broad category and does not reflect solely bills related to transparency, which is a subset of the category. You should note that the category of pharmaceutical pricing also includes matters of payment and reimbursement.

As of this week, there are now 193 bills introduced before the various state legislatures among 40 states.

How have this year’s crop fared?

As most might guess, introducing legislation is one thing, getting it passed is quite another. Bills fail because they are voted down or the session adjourns and they just expire quietly. Some fail because even though they get passed, they are vetoed. Many await their fate in committee, while others are off on the sidelines waiting for legislatures to take action then the session begins again. Here is a breakdown of the 193 bills that were introduced this year involving pharmaceutical pricing:

As you can see, there were a total of 13 bills passed, one of which is still before the state’s governor for signature and one additional passed, but was vetoed.

The bills that failed comprise nearly half of all bills introduced. Most of those passed added regulation over the activities of pharmacy benefit managers vis a vis maximum allowable cost lists – an area included in the overall topic of pharmaceutical pricing.

Two notable exceptions involved Connecticut which authorized a study of prescription drug pricing by establishing a task force that will study value-based pricing and issue a report and Vermont which provided for pharmaceutical cost transparency related to price increases. At least four other states, Massachusetts and New York, Pennsylvania and Virginia, had transparency in pricing legislation in the Pending category.

Outside of pricing, also check out the NCSL report on State Laws and Legislation Related to Biologic Medications and Substitution of Biosimilars for the most recent profile of how states are responding to the advent of FDA-approved biosimilars.

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