Everyone has returned from vacations and extended vacations and are cramming to get business done before the year end string of holidays. There is been a good deal of activity this week, so let’s get right down to it.
- FDA Establishes Docket For Opioid Feedback – Earlier this month in a posting that tracked the new directions for FDA regarding opioids, one of the items noted was the establishment of an Opioid Policy Steering Committee within FDA. While the operations and impact of the committee were unclear, it comes a little more focused this week when the agency opened a docket to receive public commentary regarding policy options for the agency. Specifically the Federal Register notice states that FDA is looking for input in three key areas: (1) what more can FDA to do ensure that the full range of available information, including possible public health effects, is considered when making opioid-related regulatory decisions? (2) what steps can FDA take with respect to dispensing and packaging (e.g., unit of use) to facilitate consistency of and promote appropriate prescribing practice? and (3) should FDA require some form of mandatory education for health care professionals who prescribe opioid drug products and if so, how should that be implemented. If you are interested in providing commentary, there will be a docket opened at regulations.gov and the docket number to search for will be FDA-2017-N-5608. Also recently posted there was the transcript from the meeting FDA held this summer on opioid policy and that can be found here.
- Breast Cancer Treatment Approval – Verzenio (abemaciclib) won FDA approval this week to treat adult patients who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer that has that has progressed after taking endocrine therapy. FDA noted it is the third drug to be approved in its class and the application has both Priority Review and Breakthrough Therapy designations.
- Glucose Monitoring Device Advancement – FDA announced approval of the first continuous glucose monitoring device which will allow people with diabetes to get needed information regarding glucose readings while reducing the need for fingerstick testing. The device uses a small, self-applied sensor that is inserted below the skin’s surface that measures and monitors glucose levels. An external reader can then determine the glucose levels and how they are changing. The device must be actively checked by the user to determine levels and does not have ability to send an alert on its own and has a 12-hour start up period and can then be worn for up to 10 days. More complete information can be found in the company release here.
- Annual Bust of Online Marketing – FDA announced this week the annual sweep of the Internet of websites engaged in the illegal marketing of prescription drugs. The agency stated that it took action against more than 500 websites that were involved in selling potentially dangerous, unapproved versions of a range of medications that included opioids among others. This was the tenth year of Operation Pangea and is part of the International Internet Week of Action – a cooperative effort of international groups of agencies. Among the action taken, FDA sent 13 Warning Letters to operators of most of the illegal sites and worked to confiscate some websites. In addition, the agency announced that it is also working on a comprehensive Enforcement operations Work Plan to combat the sale of foreign unapproved drugs and to increase the agency’s scope in this effort.
Upcoming Items to Keep an Eye on:
- Senate HELP Committee Hearing on Opioids – Among those scheduled to provide testimony are Dr. Scott Gottlieb, FDA; Dr. Francis Collins, NIH; and Dr. Brenda Fitzgerald, CDC – on October 5 – see details here.
- House Energy and Commerce, Subcommittee on Health – Hearing on October 3 examining patient access to investigational drugs – Commissioner Gottlieb among others to testify – see details here.
- Vaccines AdComm to Meet – On October 4 to consider the flu strains to be included in the next round of vaccine for 2018
That’s it for me this week folks. Enjoy the autumnal weekend.
Today marks the beginning of autumn and the summer of 2017 is over. The first turning of trees has begun and leaves and acorns are dropping on lawns. The linens have left our closets and we are beginning to think about getting all of the sweaters organized and cleaned. And most certainly, the days grow shorter. Meanwhile, as we ready ourselves to shift gears, here is a bit of what happened this week – and a new feature I would like to add – what to look for in the coming days.
- A Report and a Meeting on Antibiotics – Two items of note this week on antibiotics. First the World Health Organization issued a report stating that the world was “running out” of antibiotics and that the current pipeline offered only modifications of existing medicines while we face the development of resistant strains of infection, particularly in tuberculosis. WHO calls on the pharmaceutical industry to focus on new antibiotic development. And also this week, FDA announced the 2017 Scientific Meeting of the National Antimicrobial Resistance Monitoring System to be held on October 24-25. For those interested in participating, you must pre-register by October 10. The docket will remain open for public comment until November 24.
- FDA Statement on Medication Assisted Treatment (MAT) for Opioid Addiction – The Commissioner issued a statement yesterday regarding FDA’s efforts to support treatment for opioid addiction through medication assisted therapy – the use of medication combined with behavior therapy, where he reiterated that addressing the opioid epidemic was his “highest public health priority”. The statement highlighted the release by FDA of a Drug Safety Communication regarding MAT used in patients who are also receiving therapies where there could be a heightened potential for adverse events, and underscores the priority of treating addiction. This risk/benefit assessment is an example of weighing two risks – one involving untreated addiction and the other an adverse event caused by drug combinations – and setting a priority.
- FDA Advisory Committee Splits on Recommendation – The Oncologic Drugs Advisory Committee delivered a 6-6 vote this week after considering the risk/benefit profile of SUTENT® (sunitinib), a proposed adjuvant treatment for patients who have a high risk of cancer recurrence following surgical removal of a cancerous kidney as part of a sNDA submission. SUTENT was first approved in the U.S. in 2006 for the treatment of advanced renal cell carcinoma and has indications for GIST and advanced pancreatic neuroendocrine tumors. The company stated that an FDA decision is expected by January 2018.
- Upcoming Meetings This Month
- Peripheral and Central Nervous System Drugs Advisory Committee will meet September 28 to discuss new drug application for ataluren for oral suspension, sponsored by PTC Therapeutics, Inc. for the treatment of patients with dystrophinopathy due to a nonsense mutation in the dystrophin gene. Meeting materials will be located here.
- Senate HELP Committee Hearing on Opioids – Among those scheduled to offer testimony are Dr. Scott Gottlieb, FDA Commissioner, Dr. Francis Collins, NIH and Dr. Brenda Fitzgerald of CDC – on October 5 – see details here.
In this third, and final installment on new directions for FDA under the watch of a new Commissioner, we turn to the issue of opioids. When Dr. Robert Califf was being considered for confirmation as FDA Commissioner he faced a great deal of concerns from members of Congress about opioids, even facing a hold on his nomination over the issue. Just prior to his confirmation hearing, FDA issued an Opioid Action Plan that included a range of policy options designed to mitigate some of the risks of abuse.
However, likewise this year Dr. Scott Gottlieb made clear during this confirmation process – in answer to the same concerns being addressed by members of Congress – that addressing issues associated with the opioid epidemic in the U.S. were for him a top priority. Since then, FDA has added to the body of actions undertaken in 2016 with respect to opioids. Here is a brief overview of where we are.
- Opening Salvo – Sworn in on May 11, Commissioner Gottlieb put up his first posting on the FDA blog – FDA Voice – outlining his first steps that he was taking to address the opioid crisis. He began laying out some policy parameters, advocating for opioid prescriptions to be given only for the durations of treatment that are needed – in other words not to set up prolonged use with a prescription that goes beyond the likely therapeutic need. As a practical matter, he stated that he was establishing an Opioid Policy Steering Committee that would assemble people within the agency to consider what additional tools or strategies are needed and posed three questions to the committee – (1) Are there circumstances under which FDA should require some form of mandatory education for healthcare professionals; (2) Should FDA take additional steps under risk management authorities such as requiring the dispensing of opioids in line with the clinical need and (3) is FDA using the proper framework for considering risk and abuse in the review process? What was not clear in the posting was which internal experts served on the committee, what the makeup was, procedures for meeting and making recommendations or a timeline.
- Product Removal – A few weeks later on June 8, FDA requested the removal from market of Opana ER (oxymorphone hydrochloride) based on the concern that the benefits no longer outweighed the risks and followed FDA’s review of postmarketing data which suggested a shift in the route of abuse for the product from nasal to injection.
- Public Input on Deterrence – Five days later, Commissioner Gottlieb issued a statement announcing a public meeting to be held on July 10-11 focus a discussion on whether there is a secure understanding of whether abuse deterrent opioid products are having their intended impact – in other words – do we know if abuse deterrence deters? The transcript has been made available and is located here for the first day and here for the second, though not easy to find on the FDA site as the meeting is not posted in FDA’s Recent Meetings page.
- Next Steps – In his opening remarks to the meeting, the Commissioner gave a more complete picture of where the agency was heading by (1) looking at ways to address exposure of people to opioids – in other words – addressing the risk associated with their normal use – not opioids that are being diverted – to make sure that appropriate patients get prescribed the appropriate amount of medication for their specific clinical need, with an aim of getting fewer prescriptions written in the first lace; (2) addressing the way we go about assessing the risk and benefit of pain relief products – looking at both individual risks as well as societal risk, and (3) to look at training for prescribers and other healthcare providers involved in pain management and whether existing programs are appropriate. He also stated that FDA intends to update the existing REMS on extended release opioid products as well as on immediate release.
On July 13, the Commissioner reiterated the position that his highest priority as Commissioner is to reduce the scope of the epidemic of opioid addiction. Naturally FDA by itself cannot address the breadth and depth of this epidemic. That said, in terms of new directions, what has so far transpired is really an investigational or information gathering phase. It is almost the inverse of the announcement of an Opioid Action Plan made prior to the Califf confirmation when FDA issued several steps it was taking to address the issue. This approach is more of a process than an event.
Right now, FDA is soliciting input, conducting studies and assessing the status quo. Early indications for manufacturers are clear however, that the environment for approval and marketing is going to change and that abuse deterrence, while a factor, is not a comprehensive solution, but only a part of a greater piece of the landscape. Beyond the information gathering phase we now seem to be in, if there is to be meaningful impact, the next phase regarding opioids will be the enunciation of additional new policies and their execution.
One season winds down, another offers hints of a beginning.
I am afraid that both the regular Weekly Roundup as well as regular postings have lately been interrupted by some domestic issues that came up for me as well as a heavy travel schedule. Time to catch up – lots has happened though, and here are a few things I would bring to your attention while I get back on track:
- Mobile Medical App Approved for Many Types of Substance Abuse – This week FDA approved the first mobile medical app for use in treating substance abuse disorders. Called Reset, the app is intended for use with outpatient therapy to treat involvement with alcohol, cocaine, marijuana and stimulants, though not for use in opioid dependence. According to the FDA press release, the app contains a patient application and a clinical dashboard, supporting patients in skills intended to support abstinence and increase retention of outpatient therapy programs and will be available as a prescription-only adjunct treatment. The devise was reviewed by the agency through the de novo premarket review pathway which is for low-to-moderate-risk devices that are novel and for which there is no legally marketed predicate device which can claim substantial equivalence. Developed by a company that specializes in prescription digital therapeutics, which it refers to as “eFormulations”.
- Big Week in Oncology Medicines at FDA – Much to report here. Let’s first look to approvals. This week FDA announced approval of the first biosimilar to treat cancer. Amgen’s Mvasi (bevaczumab-awwb) (reference product is Avastin (bevaczumab)) was approved as a biosimilar, not as an interchangeable product, and is indicated for multiple types of cancer. The second piece of oncology news came from FDA in the form of an accelerated approval announcement regarding Aliqopa (copanlisib) for the treatment of adults with relapsed follicular lymphoma, a slow growing form of non-Hodgkin lymphoma that frequently recurs. Aliqopa was granted priority review and has orphan drug status. While that covers two approvals out of the pipeline this week Sandoz announced this week that FDA also accepted a proposed BLA for a biosimilar for Rituxan® (rituximab) for the treatment of blood cancers as well as rheumatoid arthritis.
- FDA’s OPDP Issues Second Letter of the Year! – Unsure as to the date of posting to the FDA site, but a Warning Letter was sent August 24 by FDA’s Office of Prescription Drug Promotion. It is notable because it is only the second letter of the year, and the first Warning Letter. The letter went to the manufacturer of an opioid product and addressed the content of a “professional detail aid” that enumerated the benefits and uses of the pain control medication while failing to mention any of the risks associated with the product use. While Warning Letters generally contain multiple violations, given the concern regarding the opioid abuse epidemic, and the dangers noted in the label which included a boxed warning and limitations on use, this letter was sent in regard only to the lack of risk information and failure to fully state the limitations of use.
- FDA AdComm Recos Approval for Shingles Treatment – On September 13, the Vaccines and Related Biological Products Advisory Committee met to consider an application from GlaxoSmithKline for its shingles vaccine candidate Shingrix and unanimously recommended approval. According to media reports, the action date for a decision by FDA on the recommendation is October.
That’s it for me this week folks. Have a good weekend and more soon.
As hurricane season made itself felt this week, summer seems over in the east. Kids are back to school and this weekend summer whites and linens have their final appearance before next Memorial Day. Meanwhile it was a very busy week for FDA – there was an approval of the first treatment of Chagas disease as well as a new antibacterial drug. All in all it was actually a rather momentous week and we capture a portion of that here.
- Approval of First Gene Therapy – “We are entering a new frontier in medical innovation…” began a quote from Commissioner Scott Gottlieb in the FDA press release this week announcing the approval of Kymriah (tisagenlecleucel) for the treatment of certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL). Indeed the approval does usher in a new era where a treatment is manufactured using patient’s own modified T-Cells to kill cancer cells and where in the clinical trial that was the basis for approval, the overall remission rate within three months of treatment was 83 percent. The treatment carries the potential for severe side effects and carries a boxed warning for potential cytokine release syndrome (CRS) which can carry high fever and flu-like symptoms. FDA also announced the expanded approval of tocilzumab to treat CRS. You can see the company digital and multimedia press release here.
- FDA Takes Action on Stem Cell Therapies – From one avenue of promising therapeutic change to another, but with a different direction – FDA announced this week enforcement actions being taken vis a vis the use of unapproved stem cell therapies in the U.S. The agency announced it had issued a warning letter to one manufacturer and a seizure of product associated with another. In a statement issued by FDA Commissioner Gottlieb, the agency also outlined new policy steps and enforcement vis a vis stem cell and regenerative therapies. In it, Commissioner Gottlieb makes clear that while stem cell and regenerative research holds a great deal of promise, the use of unapproved product stands to potentially harm patients and undermine the entire field of science, stating that the agency must separate “the promise from the unscrupulous hype” and that FDA would be stepping up enforcement while simultaneously working to ensure that responsible research is supported.
- Real World Evidence and Devices – Patient centeredness has many facets, and one of them that has been of growing interest has been the use of real world evidence in the approval of treatments for patients. Most of the focus has been on drugs, but this week FDA made available guidance – “Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices“. The guidance describes when such evidence can be used, and the criteria that must be fulfilled in order for there to be confidence int he data as well as providing some examples of actual use that have already led to FDA decisions.
That’s it for me this Labor Day Weekend. Have a good one everyone.