Drugmakers and other experts in the rare disease space urged senators to pressure the FDA to adopt a more flexible approach to the approval process for drugs intended for patients with rare or orphan diseases.
Orphan diseases are those that affect fewer than 200,000 patients. Most of these illnesses are “serious or life-threatening” and most have no FDA-approved treatment, said Sen. Rand Paul, MD (R-Ky.), during a subcommittee hearing of the Senate Health, Education, Labor and Pensions (HELP) Committee on Wednesday.
“The standard for approval for orphan drugs is similar, if not the same, as those for more common conditions. It can take upwards of a decade, sometimes, for a drug to make it from the bench to bedside, and costs can be upwards of $2 billion,” Paul said.
Because families with terminal patients can’t afford to wait for drugs to be approved, they may import drugs from other countries, take medicines off-label, or procure chemical-grade products that may be unsafe for pharmaceutical use, Paul said.
Congress has provided the FDA with “numerous tools” to speed approvals and continually increased the agency’s funding, but review times haven’t grown shorter, Paul said.
At Wednesday’s hearing, physicians, advocates and industry experts shared the barriers they face in bringing new drugs to treat rare diseases to market and proposed solutions.
“The bottom line is that we need more effective methods and pathways for drug approval for rare and ultra-rare diseases,” said Marc Patterson, MD, a professor of neurology, pediatrics, and medical genetics for the Mayo Clinic in Rochester, Minn., who advocated sweeping changes in legislation.
“What we hope to get is legislation that enables and directs the FDA to adopt specific approaches to dealing with rare diseases. To recognize they’re different. To recognize the rules that apply for common diseases don’t work,” he told MedPage Today after the hearing, when asked about his goals.
Rare Diseases are Different
Lincoln Tsang, PharmD, JD, a London-based partner at law firm Arnold & Porter Kaye Scholer, told MedPage Today the FDA needs to appreciate the context in which drugs for rare disease are being tested — which is that “there’s no drug available,” he said. “Those patients will die eventually.”
One challenge Mark Dant, chair of the EveryLife Foundation for Rare Diseases in Louisville, Kentucky, noted is that trial designs are often too narrow for patients to participate and the clinical endpoints are often very precise.
Patterson said challenges also include the already small potential pool of participants, the wide variations of symptoms, and the difficulty in measuring the effect of a drug, since traditional measures aren’t always appropriate.
Assembling a well-matched cohort of patients for controlled trials is “well nigh impossible,” Patterson said.
One solution is legislating a “menu” of options for alternative and adaptive trial designs specifically for rare diseases, Patterson said, with a smaller number of patients, perhaps 50 to 100.
Borrowing Trial Data
A second strategy Patterson urged is to have the FDA leverage data from well-controlled clinical trials “wherever they’re conducted” instead of “wasting time” duplicating the same studies state-side.
Michael Strupp, MD, professor of Neurology for the University of Munich, agreed.
If a drug is approved by the FDA, the European Medicines Agency (EMA) should approve it and vice versa, he told MedPage Today.
“That saves a lot of money, a lot of resources and there’s also much faster approval,” Strupp said.
Due to his own legislative efforts, Paul said in his opening remarks, the FDA already has the authority to accept data from other countries, but “duplicative testing and trials are still required in order to bring most drugs to market.”
“It’s still my belief that whether it’s an orphan drug or any drug… the modern civilized world is an enormous world of medicine and science now and we’re crazy to stop it at the border and say you have to Americanize all of the studies,” Paul added later.
A third recommendation Patterson put forward is to require the FDA to work with families, academic medicine, industry and other international regulatory agencies to create disease registries, containing secure patient data.
The registries can be used to enhance researchers understanding of the natural history of a disease, to develop outcome measures, and to support clinical trials.
Tsang noted that FDA regulations already include certain flexibilities, the question is whether they will test them, and be “a bit bolder.”
Reward Drugmakers
Dant, whose son Ryan was born with mucopolysaccharidosis I, advocated for Congress to pass legislation to provide incentive payments to drug companies for testing already approved products in rare diseases.
A bill known as
The Open Act would achieve such an aim by extending the exclusivity period for a drug or biologic if the drug is also approved to prevent, diagnose or treat a rare or orphan disease.
Already many patients, including his son, are taking these medications off-label without the appropriate safety, efficacy and dosing information, and many pay out-of-pocket because their treatments aren’t covered by insurers.
Dant also pressed congress to pass bills to ensure coverage of genomic sequencing.
Previous Efforts
The Orphan Drug Act of 1983, the first federal move effort to promote research for rare diseases, provided grants to help offset the costs of research and development, and granted drugmakers 7 years of exclusivity, noted Sen. Bob Casey (D-Pa.)
More recently, he and other senators helped to establish the
Rare Pediatric Disease Priority Review Voucher, which rewards drug development in the rare disease space by providing drug companies with vouchers that can be used to shorten the review time of another drug. The vouchers can also be sold and the money then reinvested in the company, Casey explained.
And in 2016, the Senate passed the
21st Century Cures Act that required the FDA to publish guidance on how to use adaptive trial designs and Bayesian methods for clinical trials.
Draft guidance was released last month, Casey said.
The agency also recently published produced a “master protocol” allowing the use of use a single clinical trial to evaluate multiple drug candidates, multiple disease types and more than one patient population in the same clinical trial.
“I really want to get a result,” Paul said at the close of the hearing, suggesting the collaboration with witnesses continue. He also voiced the possibility of updating the Orphan Drug Act with a “separate track” or a “different design.”
