FDA NewsPerspective

Treatments for cardiomyopathy from transthyretin-mediated amyloidosis approved by FDA

The FDA approved two treatments for patients with cardiomyopathy associated with transthyretin-mediated amyloidosis.

Tafamidis meglumine (Vyndaqel, FoldRx/Pfizer) and tafamidis (Vyndamax, FoldRx/Pfizer) are the first treatments for transthyretin-mediated amyloidosis that were approved by the FDA, according to a press release from the agency. Recommended doses for each treatment differ and are not substitutable on a milligram-to-milligram basis despite having the same active moiety.

The recommended dose is 80 mg once per day of tafamidis meglumine, which is given as four 20-mg capsules, and 61 mg of tafamidis once per day, which is given as a single capsule. The single-capsule formulation was developed by Pfizer for patient convenience, according to a press release from the company.

“Transthyretin-mediated amyloidosis is a rare, debilitating and often fatal disease,” Norman Stockbridge, MD, PhD, director of the division of cardiovascular and renal drugs at the Center for Drug Evaluation and Research of the FDA, said in the release. “The treatments we’re approving today are an important advancement in the treatment of the cardiomyopathy caused by transthyretin-mediated amyloidosis.”

Both formulations selectively bind to transthyretin to stabilize the tetramer of the transthyretin transport protein and reduce amyloid formation, according to the release.

The approval of both treatments was based on results from the ATTR-ACT trial. As Cardiology Today previously reported, treatment with tafamidis reduced risk for all-cause mortality and CV-related hospitalizations in patients with hereditary and wild-type transthyretin amyloid cardiomyopathy.

Tafamidis meglumine was previously granted priority review, fast track and breakthrough therapy designations by the FDA, according to the release. Both treatments were given orphan drug designation by the FDA.

Disclosures: The ATTR-ACT trial was funded by Pfizer. Stockbridge is an employee of the FDA.

The FDA approved two treatments for patients with cardiomyopathy associated with transthyretin-mediated amyloidosis.

Tafamidis meglumine (Vyndaqel, FoldRx/Pfizer) and tafamidis (Vyndamax, FoldRx/Pfizer) are the first treatments for transthyretin-mediated amyloidosis that were approved by the FDA, according to a press release from the agency. Recommended doses for each treatment differ and are not substitutable on a milligram-to-milligram basis despite having the same active moiety.

The recommended dose is 80 mg once per day of tafamidis meglumine, which is given as four 20-mg capsules, and 61 mg of tafamidis once per day, which is given as a single capsule. The single-capsule formulation was developed by Pfizer for patient convenience, according to a press release from the company.

“Transthyretin-mediated amyloidosis is a rare, debilitating and often fatal disease,” Norman Stockbridge, MD, PhD, director of the division of cardiovascular and renal drugs at the Center for Drug Evaluation and Research of the FDA, said in the release. “The treatments we’re approving today are an important advancement in the treatment of the cardiomyopathy caused by transthyretin-mediated amyloidosis.”

Both formulations selectively bind to transthyretin to stabilize the tetramer of the transthyretin transport protein and reduce amyloid formation, according to the release.

The approval of both treatments was based on results from the ATTR-ACT trial. As Cardiology Today previously reported, treatment with tafamidis reduced risk for all-cause mortality and CV-related hospitalizations in patients with hereditary and wild-type transthyretin amyloid cardiomyopathy.

Tafamidis meglumine was previously granted priority review, fast track and breakthrough therapy designations by the FDA, according to the release. Both treatments were given orphan drug designation by the FDA.

Disclosures: The ATTR-ACT trial was funded by Pfizer. Stockbridge is an employee of the FDA.

    Perspective
    Sanjiv J. Shah

    Sanjiv J. Shah

    The FDA approval is very important for patients who have ATTR-cardiomyopathy. This is the first proven treatment for this disease which is associated with high morbidity and mortality. Patients can now have access to this treatment, though its high cost may make it difficult for some patients to get access to the medication.

    Patients now have a treatment option for ATTR-cardiomyopathy that directly targets the mechanism underlying the cardiomyopathy. Hopefully the approval of tafamidis as a treatment option will lead clinicians to look for the diagnosis of ATTR-cardiomyopathy in patients with HF, particularly those who have HF with preserved ejection fraction. The diagnosis of ATTR-cardiomyopathy is often missed, but we now have noninvasive diagnostic methods such as speckle-tracking echocardiography and technetium pyrophosphate scanning that allow earlier diagnosis.

    There are several other treatments in development for ATTR-cardiomyopathy, including AG10 (a transthyretin stabilizer like tafamidis) and RNA-based therapeutics such as patisiran (Onpattro, Alnylam) and inotersen (Tegsedi, Akcea), which halt the production of transthyretin in the liver. These treatments are not yet approved but provide other potential options for this debilitating disease.

    • Sanjiv J. Shah, MD
    • Neil J. Stone, MD Professor of Medicine
      Northwestern University Feinberg School of Medicine
      Director, T1 Center for Cardiovascular Therapeutics
      Northwestern Memorial Hospital

    Disclosures: Shah reports he is a consultant for Ionis and Pfizer.