FDA Approves Multiple Ambrisentan Generics and Related REMS Programs

FDA Approves Multiple Ambrisentan Generics and Related REMS Programs On March 29, 2019, the U.S. Food and Drug Administration (FDA) approved multiple generics for Letairis (ambrisentan) tablets. With the approval of these first generics, and their associated risk evaluation and mitigation strategy (REMS) programs, patients will now have access to additional products (brand-name and generic) and additional types of pharmacies to fill their prescriptions (retail or specialty). FDA also approved two shared system REMS programs for ambrisentan. There are now two separate REMS programs for ambrisentan. The first is known as the Ambrisentan REMS (formerly called the Letairis REMS) and is comprised of the reference listed drug (RLD) or brand sponsor (Letairis), as well as three abbreviated new drug applications (ANDAs). The second program is currently comprised of one ANDA sponsor and is known as the PS-Ambrisentan REMS. The PS signifies “parallel system” to assist in differentiating the programs within the market.  A REMS is a required risk management plan that uses tools beyond the approved labeling (prescribing information) to manage risks associated with a drug. Under section 505-1 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), FDA has the authority to require a manufacturer to develop a REMS when the agency determines it is necessary to ensure that the benefits of a drug outweigh its risks.  REMS programs can be important mechanisms to mitigate serious risks and bring drugs to market that otherwise would not be approvable. The FD&C Act requires that generic manufacturers and their reference product manufacturers use a single, shared system REMS for their products, unless FDA waives that requirement and permits a separate REMS for the generic products. FDA can waive the requirement for a single, shared system if it finds that the burden of forming such a system outweighs the benefits of having one.   In this case, three generic manufacturers formed a single, shared system REMS with the brand manufacturer, utilizing the same methods of distribution as were previously used under the Letairis REMS. The other generic manufacturer did not join this system and instead proposed its own program which would allow its product to be dispensed in retail pharmacies, as well as specialty pharmacies. FDA granted a waiver of the single, shared system requirement for this generic manufacturer because it found that in this case the burden of forming a single, shared system, which would have prevented the use of retail pharmacies, outweighed the benefits. FDA also found that the separate REMS proposed by the generic manufacturer achieves the same level of safety as the REMS for the brand-name ambrisentan. For more information on the formation of single, shared system REMS and waivers of the single, shared system REMS requirement, see FDA’s guidances on these topics: Development of a Shared System REMS and Waivers of the Single, Shared System REMS Requirement.