FDA clears Amneal’s ready-to-use romidepsin, filling gap left by Teva’s withdrawal

The FDA has approved Amneal Pharmaceuticals’ romidepsin, a ready-to-use injection to treat adults with cutaneous T-cell lymphoma and who have received at least one prior systemic therapy. Romidespin is eligible for competitive generic therapy (CGT) designation, which provides Amneal with 180 days of market exclusivity.

Cutaneous T-cell lymphoma is a type of cutaneous non-Hodgkin lymphoma (NHL). In cutaneous T-cell lymphoma, T-cells, a type of lymphocyte that plays a role in the immune system, become cancerous and presents as red, scaly patches on the skin. It is more common among men than women, with an average age of onset between 50 and 60 years of age. It is generally a slow-growing cancer but in rare cases can spread to lymph nodes and internal organs.

Romidepsin is a histone deacetylase inhibitor. It is available as 27.5 mg/5.5 mL and it is supplied in single-dose, ready-to-use vials. Romidepsin is available on the U.S. market under the brand name Istodax and marketed by Bristol Myers Squibb. But Istodax must be reconstituted, and it is supplied as part of a kit.

Amneal’s ready-to-use formulation of romidepsin references the romidepsin product that was previously marketed by Teva. Teva’s withdrawal of romidepsin was tied to the withdrawn of an indication to treat patients with peripheral T cell lymphoma. In 2011, Celgene, now a subsidiary of Bristol Myers Squibb, received accelerated approval for the peripheral T cell lymphoma indication. The approval was based on results from two clinical studies that assessed the effect of Istodax on the surrogate end point of overall response rate.

Bristol Myers Squibb conducted a confirmatory phase 3 study evaluating Istodax plus a combination regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) versus just CHOP as a first-line treatment of PTCL patients, but results from the trial showed that Istodax did not meet the primary efficacy end point of progression-free survival.

After Istodax and Teva’s generic lost the indication for peripheral T cell lymphoma, Teva made the decision to withdraw the ready-to-use formulation, but this decision was not made for safety or effectiveness reasons, according to a Federal Register notice.

The most common adverse reactions associated with romidepsin injection solution include nausea, fatigue, infections, vomiting, anorexia, electrocardiogram ST-T wave changes, dysgeusia, constipation and pruritus. Grade 3 and 4 laboratory abnormalities include lymphopenia, neutropenia, anemia and thrombocytopenia.