FDA Explains Why it Waived a Shared REMS for Letairis Generics

Regulatory NewsRegulatory News | 06 May 2019 |  By 

The US Food and Drug Administration (FDA) has released a memorandum explaining why it waived the requirement of a single, shared system (SSS) risk evaluation and mitigation strategy (REMS) for generic versions of Gilead’s Letairis (ambrisentan), which treats pulmonary arterial hypertension. This is just the fourth time in FDA’s history that it has waived an SSS REMS for generic competitors.

Because the process of creating an SSS can be time-consuming and complex, such a determination to waive an SSS REMS by FDA can only occur when the agency decides that the burden of creating an SSS outweighs its benefits.

In the case of Letairis, FDA highlighted the disagreements between Gilead and several generic drug sponsors over what the SSS would look like.

“The RLD Sponsor (Gilead) rejected the ANDA sponsors’ proposal to include all pharmacies willing to meet REMS certification requirements under the shared REMS program. The RLD Sponsor firmly maintained the view that ambrisentan should solely be available through the use of specialty pharmacies. Thus, a mutually agreeable solution could not be attained. Consequently, Gilead suggested that the ANDA sponsors seek a waiver request,” the memorandum says.

Last May, as part of a strategy to combat the exploitation of REMS programs to keep generics off the market, FDA drafted a guidance on the conditions under which it would issue waivers for an SSS requirement, and how generic drug applicants can request a waiver.

In the case of Letairis, FDA explained further: “While a SSS would provide benefits to stakeholders by avoiding the potential confusion and inefficiency associated with the existence of two REMS for ambrisentan, these benefits do not outweigh the burdens of (1) the time and resources expended by the AARG [generic] applicants and the RLD to create a SSS REMS, (2) a delay in the approval of additional safe and effective generic ambrisentan alternatives, and (3) limiting access to generic ambrisentan by preventing its dispensing by retail pharmacies.”

But FDA also explains how the existence of two REMS programs will create some inefficiencies for prescribers and some pharmacies.

“Both REMS require that prescribers and pharmacies be certified in the REMS program. Therefore, prescribers who want to prescribe both Letairis and generic products that are in the waiver-granted REMS will have to certify in both programs. Prescribers will also have to enroll some patients in both programs if they switch between a product in the RLD REMS and a product in the waiver-granted REMS for any reason, including because the patient chooses to use retail pharmacies or due to insurance provider preferences,” FDA explains.


The agency has previously waived the SSS REMS requirement in three other cases: for Jazz Pharmaceuticals’ Xyrem (sodium oxybate) in January 2017, Prometheus Laboratories’ Lotronex (alosetron hydrochloride) in April 2015 and Reckitt Benckiser’s Suboxone (buprenorphine-naloxone tablets) in February 2013. In all three cases, the lengthy negotiating periods for reference product and generic sponsors played a role in FDA’s decision to waive the shared REMS requirements.

In the case of Lotronex, SSS negotiations were underway for approximately eight months before generic drugmaker Roxane concluded that further negotiations were fruitless. And FDA noted that this inability to agree to SSS terms and submit a joint SSS REMS “could indefinitely delay the approval of a generic version of alosetron.”

And the negotiations over an SSS REMS for sodium oxybate were “substantially longer” than the negotiations for alosetron or buprenorphine, FDA said.

Letairis memorandum


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