Opioid painkiller benefits fall short of abuse risks

The benefits derived from the use of Endo International Plc’s opioid drug no longer outweighs its risks, according to an FDA advisory panel. As opioid abuse, overdose and addiction have reached epidemic proportions in the United States, partly due to unrestricted prescription of narcotic painkillers, as well as the paucity of access to substance-abuse treatment programs, the FDA has undertaken review of the uses of the painkiller in a variety of settings. Eighteen panelists recommended that the risks of the reformulation eclipse the benefits, while eight disagreed and one member abstained from voting. The FDA generally follows advisory panel recommendations, but is not required to do so.

The FDA advisory panel reviewed the abuse rate of Endo’s Opana® ER – a long acting painkiller similar to oxymorphine and other oxymorphone drugs. Opana was approved in 2006, and in 2012, the drug maker introduced a new formulation to attempt to deter abuse of the drug. Although the reformulation (in nasal form) reduced abuse rates, intravenous abuse increased in the same timeframe. The panel was unable to conclude whether this rise was related to the reformulation, but noted that the trend was observed before the reformulation. Additionally, abuse rates for similar oxymorphone drugs are as high as Opana.

One factor that triggered the advisory panel’s review was the increased rate of rare blood disorders and human immunodeficiency virus (HIV) linked to the IV abuse of the reformulation.

Some advisory panel members expressed concerns that the voting question posed did not permit consideration of the risk-benefit profile for an intended user versus use by an addict. Others questioned whether withdrawing the product would stop an addict from abusing other opioids, or whether oxymorphone was still an integral part of the arsenal of treatments for chronic pain.

 

FDA considers establishing a new ‘Office of Patient Affairs’

The FDA announced that it is establishing a public docket to solicit public input on ongoing efforts to enhance mechanisms for patient engagement at the agency. In addition, to achieve a more transparent, accessible, and robust experience for patient communities, the FDA is considering establishing a new Office of Patient Affairs.

On November 4, 2014, the FDA established a docket (FDA-2014-N-1698) for the public to submit information related to the FDA’s implementation of the Food and Drug Administration Safety and Innovation Act (FDASIA) (P.L. 112-144), Patient Participation in Medical Product Discussions under FDASIA section 1137.

Based on the comments received, the FDA identified objectives for its patient engagement activities. First, to develop a nuanced understanding of the patient experience of disease by: (1) gathering patient perspective on what is clinically meaningful; (2) assessing attitudes towards benefit-risk and tolerance of uncertainty; and (3) enhancing the science of eliciting and integrating patient input.

Second, to support patients and their advocates in understanding regulatory processes and navigating the FDA by: (1) communicating relevant FDA positions, procedures, and activities; (2) connecting patients and their advocates with the appropriate resources; and (3) resolving discrete challenges and needs.

To achieve these objectives, the FDA is considering establishing a central “Office of Patient Affairs.” The responsibilities of this central office would include:

  • offering a single, central entry point to the FDA for the patient community;
  • providing triage and navigation services for inbound inquiries from patient stakeholders;
  • hosting and maintaining robust data management systems that would incorporate and formalize knowledge shared with the FDA by patient stakeholders and the FDA’s relationships with patient communities; and
  • developing a scalable and forward-looking platform for communicating with patient stakeholders, particularly online channels.

The Office of Patient Affairs would be directly accountable to the medical product Centers. A regular evaluation of this central office and of FDA’s overall patient engagement efforts are also proposed.

 

 

Trump nominates Gottlieb for FDA Commissioner

President Trump intends to nominate Scott Gottlieb, M.D., a resident fellow at the conservative American Enterprise Institute (AEI), clinical assistant professor at New York University School of Medicine, and a member of the HHS Federal Health IT Policy Committee, to the post of FDA Commissioner. The White House announced the nomination, which brought varied reactions from opposite sides of the aisle and a general positive response from the pharmaceutical industry, via a tweet from Press Secretary Sean Spicer.

Gottlieb served as the Deputy FDA Commissioner from 2005 to 2007 and previously served as a senior official at CMS. He has testified before Congress on numerous occasions as an AEI felllow, most recently with respect to EpiPen® price increases and “How Regulatory Barriers Inhibit Pharmaceutical Competition.” Gottlieb noted that FDA regulatory policy has made developing less expensive copies of complex drugs after patent expiration difficult, discussed how the 340B program has put “upward pressure on drug prices,” while noting other change in drug insurance coverage structure, and described obstacles to competitive single source drug pricing.

Various sources report that Gottlieb has close ties to the pharmaceutical industry. Scientific American noted that Gottlieb believes in a quicker approval process for new drugs, but has focused on shortening waiting times for large, clinical trials rather than doing away with efficacy considerations. He commented on this, to an extent, in remarks he made at the 21st Annual International Meeting of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) in May 2016.

Gottlieb has also issued commentary about the Patient Protection and Affordable Care Ac (ACA) (P.L. 111-148). In May 2016, he testified before Congress that the law’s tiered marketplace approach has aided consumers with plan selection, but has forced insurers into narrow design corridors. His testimony regarding the ACA also included a suggestion that CMS move away from mandates and towards incentives to encourage individuals to enter into the insurance market (see Is there a better way than the ACA? Hearing asks experts, Health Law Daily, May 12, 2016). More recently, he coauthored a piece with another AEI fellow, opining that President Trump’s election provided, “a generational opportunity to pursue a new direction for American health care” and making suggestions about how a new health care system should operate. The authors suggested that the system should provide a path to catastrophic health insurance for all, accommodate individuals with pre-existing health conditions, allow access to health savings accounts, and deregulate the medical services market.

Senator Lamar Alexander (R-Tenn), Chairman of the Committee on Health, Education, Labor & Pensions, touted Gottlieb’s “impressive qualifications” in a released statement. His colleague, Ranking Member Patty Murray (D-Wash), expressed “initial concerns” about the nomination, including Gottlieb’s “work with multiple pharmaceutical companies, medical device companies, and investment firms.”

User fee program reauthorizations necessary for product development

The House Energy and Commerce Subcommittee on Health focused its attention on the FDA’s generic drug and biosimilar user fee programs by inviting the FDA and industry leaders to a hearing to discuss how the programs have been implemented to date and recommendations on reauthorization. Both the Generic Drug User Fee Amendments of 2012 (GDUFA) and the Biosimilar User Fee Act of 2012 (BsUFA) expire in September 2017 and must be reauthorized for the Fiscal Years 2018 to 2022. The hearing also discussed H.R. 749, the Lower Drug Costs Through Competition Act, which seeks to increase generic competition through a shortened review cycle of six months.

Background

Since 1992 and based on the Prescription Drug User Fee Act (PDUFA), Congress has authorized the FDA to collect fees from regulated industry to supplement congressional appropriations. Revenues generated from these fees have been used on specific activities related to the review and regulation of medical products. In exchange for industry agreeing to pay fees, the FDA agrees to meet certain performance goals, such as completing product reviews within specified timeframes. Industry concerns about the length of time it was taking the FDA to review generic drug applications, known as abbreviated new drug applications (ANDA), and the backlog of such applications pending at the agency led Congress to pass GDUFA as part of the Food and Drug Administration Safety and Innovation Act (FDASIA).

Likewise, the Biologics Price Competition and Innovation Act (BCPIA) of 2009, as passed with the Patient Protection and Affordable Care Act (ACA) (P.L. 111-148), established a new regulatory authority for the FDA to create an abbreviated approval pathway for biological products demonstrated to be “highly similar” to, or “interchangeable” with, a previously licensed biological product. As part of FDASIA, Congress passed BsUFA to authorize FDA to collect user fees from biosimilar product manufacturers.

Pew Charitable Trusts

Allan Coukell, Senior Director of Health Programs, The Pew Charitable Trusts presented testimony on rising pharmaceutical costs, within and beyond the user fee context. He noted the rising cost of new medicines—especially high-cost specialty drugs, which are only used by 1 to 2 percent of the population, but account for more than one-third of drug spending. Although the FDA’s approval processes outlined in the generic and other user-free agreements offer some potential to address drug spending, he stressed that competition via generic drugs.

As such, the Lower Drug Costs through Competition Act (H.R. 749) would award a generic priority review voucher to any manufacturer that brings a generic drug to market in cases of limited competition or a drug shortage. It would also establish a six-month timeline for FDA review of priority applications, faster than the GDUFA review. In addition to accelerated review, the Pew Charitable Trusts called for Congress to consider requiring greater transparency of contract terms and definitions between payers and pharmacy benefit managers (PBM), as well as mandating the ability to audit these deals, and ensuring that entities that advise purchasers on PBM contracts do not also have financial relationships with the PBMs themselves.

Association for Accessible Medicines

David Gaugh, Senior Vice President for Sciences and Regulatory Affairs at the Association for Accessible Medicines (AAM), which was previously known as GPhA—the trade association representing the manufacturers and distributors of generic prescription drugs, manufacturers and distributors of bulk pharmaceutical chemicals—testified that the best way of achieving the goal of providing patients access to generic alternatives is through the development of policies that promoted competitive markets. The AAM stressed that the best way to control drug costs generally was through policies that incentivize competition, such as GDUFA.

The user fee program supports small business by exempting them from a facility fee until the first ANDA in that facility is approved. The proposal also provides for a tiered structure of annual ANDA program fees based on small, medium, and large companies. Designing GDUFA to spread fees across industry to keep individual amounts as low as possible, the AAM believed the program would help assure that patients continue to receive the significant cost savings from generics alternatives.

Biotechnology Innovation Organization

Kay Holcombe, Senior Vice president, Science Policy, Biotechnology Innovation Organization (BIO), offered testimony to the Subcommittee on reauthorization of BsUFA and H.R. 749. BIO supported the reauthorization of BsUFA, as well as expressed its support for competition in the prescription drug marketplace not only between innovator biologics and biosimilars, but also between innovator drugs and generic drugs, which is the subject of H.R. 749. BIO urged the FDA to lay out its thinking on interchangeability and believed it was crucial for the FDA to clarify its expectations for the data needed to determine that a biosimilar product is interchangeable with its reference biological product. Such a determination could serve to encourage greater prescribing and use of biosimilars as the availability of biosimilar products increases, provided the determination is sufficiently rigorous.

As for H.R. 749, BIO did not adopt a position on the question of timelines for generic drug review or awarding certain generic drug applicants with priority review vouchers under the proposed legislation. BIO did note that it supported policy intended to lower drug prices through the promotion of competition in the drug marketplace, including the timely entry of generics and biosimilars once patents and exclusivities for innovator drugs have expired.

Biosimilars Council

Bruce Leicher, Senior Vice President and General Counsel at Momenta Pharmaceuticals, and Chair of the Biosimilars Council Board of Directors, a division of AAM, noted that the BsUFA reauthorization user fees were now tied to the level of resources needed and adjust with resource demand. As such, it was vital that Congress understood that the funding provided by user fees is in addition to, not a substitute for, congressional appropriations.

Biosimilars Forum

Juliana Reed, Vice President of Government Affairs for Coherus BioSciences, stated that the Biosimilars Forum entered into the BsUFA reauthorization negotiation process with four primary goals: (1) ensuring solid financial support for the program; (2) improving communication between the FDA and biosimilars product sponsors during the approval process to improve efficiency; (3) increasing transparency during the approval process and regarding the spending of user fees; and (4) preventing the expenditure of BsUFA funds on extraneous policy issues or activities that are not exclusive to biosimilars. The Biosimilars Forum was pleased to see that the BsUFA draft met these goals.

In addition, the Biosimilars Forum urged Congress require CMS to review its current reimbursement policy for biosimilars and make it consistent with FDA biosimilar policies. Specifically, it noted that the FDA policy on biosimilars acknowledges the unique nature of each biosimilar, and CMS should align its policy by assigning unique, individualized billing codes to each biosimilar.

FDA

Janet Woodcock, Director of the Center for Drug Evaluation and Research (CDER) at the FDA, discussed both GDUFA and BsUFA during her testimony before the Subcommittee. GDUFA achieved a number of notable goals during the course of its five-year authorization. The FDA approved or tentatively approved 835 ANDAs—the most approvals in the history of the agency—in fiscal year (FY) 2016 alone. The previous high was 619. In addition, approximately 25 percent of all currently approved generic drugs were approved over the past four years. Prior to GDUFA, ANDAs were approved in one review cycle less than one percent of the time. Now, approximately nine percent of ANDAs are approved in the first review cycle.

The FDA did note some challenges to GDUFA, namely submission completeness and volume of applications. Historically, it has taken on average about four review cycles to approve an ANDA as a result of deficiencies by generic drug sponsors in submitting complete applications. More work by both the FDA and industry will be necessary to have the filings be accurate the first time. Moreover, in FYs 2012, 2013, and 2014, the FDA received over 1,000, nearly 1,000, and nearly 1,500 applications, respectively, which taxed the agency’s ability to timely process the ANDAs.

The FDA was also supportive of and fully engaged with the development and approval of biosimilar and interchangeable products. One of the first steps in the development and review process for a biosimilar is for an applicant to join the FDA’s Biosimilar Product Development (BPD) Program. As of February 2017, 64 programs were enrolled in the BPD Program and CDER has received meeting requests to discuss the development of biosimilars for 23 different reference products. Moreover, the FDA finalized six guidances and issued four draft guidances during the timeframe in question. The FDA’s challenge, however, was a result of staffing shortages. Without additional staffing to handle the increased workload for biosimilar review, the FDA warned that review performance would be impacted.