Jill Wechsler is Pharm Exec's Washington Corespondent

Jill Wechsler

	Can a commitment to limit prices to ensure patient access to important new medicines regain public trust and confidence in the biopharmaceutical industry? That’s the hope of a large cadre of biotech company executives who recognize that recent scientific advances that promise to cure critical diseases must be linked to high integrity and corporate responsibility or face price controls and other policies that undermine support for continued discovery of new medicines. 

	In a “New Biotechnology & Pharmaceutical Industry Commitment to Patients and the Public” penned by six CEOs, more than 200 leaders from some 150 small and mid-size firms and research organizations 

acknowledge that out-of-pocket costs for individuals must be limited to sustain support for fiscal and patent policies key to advancing innovation

. The group led by executives from Amicus, Nkarta, Ovid, Global Blood, GlycoMimetics and Alnylam Pharmaceuticals back collaboration with healthcare entities, including payers, hospitals, and distributors, in efforts to eliminate co-pays and deductibles for all patients. 

	Those signing the commitment letter also pledged to support ethical business practices and to invest “only in novel therapies that address unmet patient needs.” And they oppose companies and stakeholders who “abuse this commitment to patients and who abuse policies aimed at fairly rewarding innovation.” At the same time, the group supports the marketing of biosimilars and generic drugs after “legitimate patents and regulatory protections expire.” 

	By itself, the public letter offers few specifics for effective change in current industry practice. Even so, the list of supporters is notable for the absence of big pharma and biotech firms who did not sign on, ostensibly due to legal concerns about joining any industry initiative that could be construed as involving multi-company price-setting agreements. The Biotechnology Innovation Organization (BIO) voiced support for the principles expressed here by many of its members, but did not officially endorse the statement. And while manufacturers can face stiff penalties for actions even hinting at price-setting agreements, these commitments to ethical practices should avoid such consequences by emphasizing responsible actions by individual companies. 

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More than 200 biopharma leaders acknowledge that out-of-pocket costs for individuals must be limited to sustain support for fiscal and patent policies key to advancing innovation.

Biotech Execs Pledge “Reasonable” Price Increases

	FDA did not set any records last year in approving new drugs and biologics for market, but it did speed a number of important new therapies to patients, in continuing to demonstrate its flexibility and support for biomedical innovation. Based on its criteria, the Center for Drug Evaluation and Research (CDER) approved some 50 new molecular entities (NMEs) in 2019, a count that may vary 

. In addition, the Center for Biologics Evaluation and Research (CBER) approved the first gene therapy for spinal muscular atrophy, Novartis’ Zolgensma, as well as new vaccines for Ebola (from Merck) and Dengue (Sanofi). While the totals fall short of the record-setting 59 NMEs approved in 2018, the numbers are close to or exceed the agency’s performance in most previous years. 

	Probably more important than the number is the wide range of break through therapies moving through the agency’s review process, including nearly a dozen cancer treatments, some with innovative modalities. Speedy approvals at the end of the year included the first PARP inhibitor to treat advanced pancreatic cancer, Lynparza, from AstraZeneca and Merck. FDA also approved two antibody-drug conjugates (ADCs), one for urothelial cancer from Seattle Genetics and Astellas Pharma, and another for advanced breast cancer from Daiichi Sankyo and AstraZeneca. 

	Earlier, Vertex Pharmaceuticals gained a fast approval for a new triple-combo treatment for cystic fibrosis, Trikafta, while new therapies for complicated urinary tract infections came from Shionogi and Merck. Particularly noteworthy is the success of two new drugs for sickle cell disease, which largely affects African Americans. These include Novartis’ Adakveo and Oxbryta from Global Blood Therapeutics. The list also includes important new drugs for postpartum depression from Sage Therapeutics, Intra-Cellular’s Caplyta for schizophrenia in adults, new migraine therapies from Eli Lilly and from Allergan, plus a new Novartis drug for a relapsing form of multiple sclerosis. 

	Most surprising was FDA’s decision in December to approve Sarepta Therapeutics’ second drug for Duchenne muscular dystrophy, Vyondys 53. The agency had rejected the application only four months earlier. 

	Speedy review from FDA, as well as high launch prices for many critical new drugs, will continue to raise controversy. Some critics claim the agency is moving too quickly in bringing new therapies to market based on limited testing, while others argue that FDA remains too slow in addressing the critical needs of many patients. And high price-tags, particularly for some treatments for larger patient populations such as sickle cell disease, are sure to accelerate calls for pharmaceutical price controls. So far, Congress has stepped back from legislation to limit outlays for prescription drugs, but the debate will be aggravated by a number of new medicines with six-figure annual costs, as well as a large number of annual January increases in list praises for hundreds of brand medicines.  

While not setting any records for the rapid approval of new drugs in 2019, FDA did speed a number of important new therapies to patients, writes Jill Wechsler.

New Drug Approvals Stay Strong in 2019

	FDA has an official new leader, following a Senate vote to confirm Stephen Hahn as the agency’s next commissioner. Hahn comes to FDA from the MD Anderson Cancer Center in Houston, where he was chief medical officer. Despite his lack of experience in the federal government, he benefited from broad support from dozens of patient groups and research entities, as well as a strong list of five former FDA commissioners. Regulated entities and most stakeholders affected by FDA programs usually prefer that the agency have a clear leader, as opposed to less authoritative temporary directors. 

	Hahn lost some support in the Senate from Democrats due to a limited commitment to taking action to against teen vaping of flavored e-cigarettes, a controversial area that has suffered from unclear administration policy. At the same time, Hahn demonstrated his political skill by indicating strong interest in numerous hot policy issues during his Senate confirmation hearings, without making clear commitments to specific actions. 

	Although Hahn’s role at FDA may be short-lived if there is a change in administration next November, he faces a broad range of hot-button issues that require more immediate attention. FDA is under pressure to do more to address the deadly opioid epidemic, to weigh importation of less expensive drugs from other countries, to clarify polices for marketing cannabidiol products, and for supporting the development of new breakthrough therapies filling the new drug pipeline. A main task for the commissioner is to make the case to Congress and the administration for strong funding for FDA, despite partisan hostility on Capitol Hill and administration efforts to cut federal spending. And the high cost of new cutting-edge therapies will remain a high-profile issue, raising questions about FDA vetting of the long-term benefits and risks of new treatments.

FDA has an official new leader, following a Senate vote to confirm Stephen Hahn as the agency’s next commissioner. 

Hahn Confirmed as FDA Commissioner

	The development of new therapies to treat orphan diseases is particularly perilous, due to limited patient populations, high costs, and difficulty in measuring clinical effectiveness. FDA officials are addressing these issues through the Rare Disease Cures Accelerator (RDCA) initiative in the Center for Drug Evaluation and Research (CDER). The goal is to shift away from a system of fragmentary research methods plagued by poor quality evidence to a more coordinated research approach and methods that can expedite development of drugs to treat some of the 7,000 rare diseases affecting 25,000-30,000 people. 

	Main strategies involve establishing common platforms and standardized tools and infrastructure to improve the quality of clinical trial data, explained Theresa Mullin, CDER acting director for strategic initiatives, at the “rare summit” sponsored by the National Organization for Rare Disorders (NORD) in Washington, D.C. last week. Mullin described how a more cooperative and collaborative approach can improve the quality of study endpoints, promote trial designs that accelerate learning, reduce mis-steps that cause failures and delays, and generate evidence needed for regulatory approval.

	The RDCA provides the infrastructure for a cooperative approach to designing and conducting clinical trials in rare diseases to improve testing, protocols, and patient enrollment in clinical trials, Mullin noted. FDA is collaborating with the Critical Path Institute, NORD, patient groups, industry and other stakeholders on a framework for conducting more standardized rare disease natural history studies to help target treatment and design appropriate clinical trials. This involves examining the underlying causes of a disease, how it changes over time, variables in symptoms and experiences, and how the disease differs across patient populations. Patient perspectives remain key to providing insight into the most important impacts and what constitutes “meaningful change” in symptoms. 

	Similarly, the RDCA Data Analytics Platform (DAP) aims to house integrated patient-level data from diverse sources, including clinical trials, observational studies, patient registries and real-world data from electronic health records, noted FDA acting commissioner Ned Sharpless at the NORD conference. A goal of the initiative, he pointed out, is to facilitate sharing of existing patient-level data to inform disease characterization and clinical trial design to accelerate development of new rare disease therapies. 

	Another key RDCA component involves devising core sets of clinical outcomes assessments (COAs) to measure treatment impacts that matter most to patients and ideally are applicable to more than one rare disease. A new CDER grant program supports the development of core COAs and related endpoints, including those impacts that matter most to patients and are likely to demonstrate change. 

	A more long-term RDCA goal is to establish a global clinical trials network able to facilitate the launch and conduct of studies involving rare diseases, Mullins added. Investigators and sites in the network would provide more uniformity and expertise in planning and conducting studies for rare disease therapies and ensure the collection of high quality data.

	The RDCA initiative is supported by some of the $10 million in last year’s FDA budget provided by Congress to support innovation in advancing treatments for rare diseases. FDA’s Office of Orphan Products Development (OOPD) recently awarded two grants for natural history studies at academic research centers, one measuring acute pain in infants and young children, and the other assessing physical function across a range of chronic conditions. And 12 new grants to fund clinical trials involving rare disease therapies, building on FDA’s long-standing program to support researchers conducting clinical trials in this area, particularly to advance treatments for pediatric rare diseases. 

	On a broader level, RDCA initiatives aim to advance common approaches and more sharing of research goals and methods to build on commonalties for developing new orphan drug therapies, Sharpless observed. He noted that FDA will continue to provide expedited review pathways for promising rare disease treatments and will issue more guidance documents to spur development of new pediatric medicines and gene therapies for rare diseases. And researchers receiving orphan products grants from FDA will contribute to discussions of common considerations for successful completion of rare disease studies. 

CDER's Rare Disease Cures Accelerator initiative looks to foster a coordinated research approach and methods that can expedite development of drugs to treat some of the 7,000 rare diseases. 


Author | Jill Wechsler