FDA Approves First Generic Versions of Letairis (ambrisentan) and Related REMS Programs - Drug Information Update

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, or generics). 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.

For patients to access these additional options, there are important actions items for prescribers, patients and pharmacists should complete. 

Prescribers of ambrisentan should:

• Ensure they are enrolled in both programs by enrolling in the PS-Ambrisentan REMS. Prescribers currently enrolled in the Letairis REMS will be automatically enrolled in the Ambrisentan REMS. This will allow their patients to have access to both generic and branded ambrisentan and to receive their medication from multiple pharmacy types, depending on their insurance coverage.   
• Enroll their current ambrisentan patients in the PS-Ambrisentan REMS. Patients currently enrolled in the Letairis REMS will be automatically transferred to the Ambrisentan REMS.
• Enroll all future ambrisentan patients in both the Ambrisentan REMS and the PS-Ambrisentan REMS.

Patients who take ambrisentan should: 

• Complete enrollment in the PS-Ambrisentan REMS with their prescriber. Patients currently enrolled in the Letairis REMS will be automatically transferred into the Ambrisentan REMS. If patients are not enrolled in both programs, their access to both generic and brand-name Letairis and/or their ability to receive their medication from either retail pharmacies or specialty mail order pharmacies may be limited.
• Confirm insurance coverage of prescribed ambrisentan.
• Understand they may be contacted by both programs during treatment to confirm pregnancy test requirements, especially if patients switched from brand to generic product or between generic products.  

Pharmacies that dispense, or plan to dispense, ambrisentan should: 

• Be aware of both programs.
• One program, the PS-Ambrisentan REMS, will allow ambrisentan to be filled in the retail setting, while the Ambrisentan REMS (formerly Letairis REMS) will continue to only utilize specialty pharmacies. 
• Each program will have procedural requirements specific to their REMS program.  
• All pharmacies that currently dispense Letairis will need to re-enroll into the Ambrisentan REMS for continued access to ambrisentan. The Ambrisentan REMS will contact all currently certified pharmacies to assist with this process.  Pharmacies who wish to dispense ambrisentan in the retail setting or who wish to have access to all the generic manufacturers should also enroll in the PS-Ambrisentan REMS. 
• Inpatient pharmacies may wish to enroll in both programs to ensure continued access to all manufacturers of brand-name and generic ambrisentan.
• Outpatient pharmacies may choose to enroll in one or both programs. The two programs differ in the methods of distribution in outpatient settings.
• Specialty pharmacies enroll and distribute product through the Ambrisentan REMS and/or the PS-Ambrisentan REMS.
• Retail pharmacies enroll and distribute product through the PS-Ambrisentan REMS.   

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.