Scott Gottlieb, MD, commissioner of the FDA, who has been vocal about "shenanigans" used by innovator drug makers to forestall competition from biosimilars and generics, today announced the publication of a list of companies that have restricted access to samples of small-molecule drugs for testing through the use of Risk Evaluation and Mitigation Strategies programs or limited distribution of their products.
Scott Gottlieb, MD, commissioner of the FDA, who has been vocal about “shenanigans” used by innovator drug makers to forestall competition from biosimilars and generics, today announced the publication of a list of companies that have restricted access to samples of small-molecule drugs for testing through the use of Risk Evaluation and Mitigation Strategies (REMS) programs or limited distribution of their products.
“We’re taking these steps today because we believe greater transparency will help reduce unnecessary hurdles to generic drug development and approval,” said Gottlieb, noting that the agency has fielded more than 150 inquiries from drug makers concerning difficulty in obtaining samples for testing.
REMS programs, which manage potential risks of a drug, have come under scrutiny as potential avenues for anticompetitive behavior in the marketplace. Some stakeholders warn that REMS programs are used by some drug makers to improperly withhold samples of products for testing by biosimilar or generic drug developers, even in cases in which the FDA has informed a drug company in writing that it will not consider provision of samples to be a violation of a REMS program.
Furthermore, when a REMS program includes Elements to Assure Safe Use (ETASU), the FDA requires the generic or biosimilar product applicant and originator to use a single, shared REMS system to implement the ETASU before the generic or biosimilar’s application may be approved (though the FDA may waive the single, shared system requirement in some cases). Prolonged negotiation over the nature of the shared system can potentially be used by reference product sponsor to delay approval of a competing drug.
Limited distribution networks, which are established when a drug maker contracts with either 1 or a limited number of distributors, can allow a manufacturer to efficiently manage the supply chain for a given product, but may also be used to apply contract terms that a particular drug only be sold to individual patients, not to generic or biosimilar developers, again blocking the sale of product samples for testing.
Among the drugs that were subject to the greatest number of letters to FDA concerning sample availability were 2 drugs for the treatment of pulmonary arterial hypertension: Actelion’s bosentan (Tracleer), which was the subject of 14 letters, and Gilead’s ambrisentan (Letairis), which was the subject of 10 letters. Other drugs that were the subject of communications numbering in the double digits included 2 Celgene products: lenalidomide (Revlimid) for the treatment of myelodysplastic syndrome, multiple myeloma, and mantle cell lymphoma, was the subject of 13 letters, and thalidomide (Thalomid) for the treatment of leprosy and multiple myeloma, was the subject of 10 letters. Only small-molecule drugs were included in the list published today; biologics and their product sponsors were not named.
Gottlieb signaled that publication of the list alone would not be enough to stop the withholding of samples: “There isn’t 1 single action that’s going to solve this issue,” he said. “We will achieve these public health goals through the coordinated effort of different federal agencies working in partnership with industry and other stakeholders.” He added that the FDA is working with the Federal Trade Commission on this matter.
Some stakeholders question whether the FDA’s push for greater transparency will be effective as a tactic. Chip Davis, president and CEO of The Association for Accessible Medicines (AAM), said in a statement given to The Center for Biosimilars® that, while transparency is an important first step, “Pharma companies are inured to shaming.”
According to Davis and the AAM, Congressional action—namely, the passage of the bipartisan Creating and Restoring Equal Access to Equivalent Samples (CREATES) Act—will be the key to putting a permanent end to the withholding of samples. The Act, sponsored by Senator Patrick Leahy, D-Vermont, would allow a generic or biosimilar drug developer to bring a civil action against the license holder of a reference drug if the latter declines to make available enough samples for testing. Similarly, the developer could bring an action if the reference product’s sponsor fails to agree upon (or allow a competitor to join) a single, shared system of REMS with ETASU.
Davis added that he was encouraged that Speaker of the House Paul Ryan, R-Wisconsin, has said that he will work to pass the bill, but added that “It’s important that Congress gets this right: any compromise must ensure the timely approval by FDA of safe, effective and more affordable versions of pricey brand medicines. Any compromise must also provide strong enough enforcement to deter bad actors from gaming the rules that were never intended to be used to protect their monopoly at the expense of patients.”