FDA Advisers Say 'No' to Myeloma Drug

Published: Nov 6, 2014

By Charles Bankhead, Staff Writer, MedPage Today

WASHINGTON -- An FDA advisory committee voted not to recommend approval of the histone deacetylase (HDAC) inhibitor panobinostat for second-line treatment of multiple myeloma.

Positive results from two different clinical trials failed to persuade the Oncologic Drugs Advisory Committee (ODAC) that the combination of panobinostat, bortezomib (Velcade), and dexamethasone warranted approval for treatment of myeloma that had relapsed or proven refractory to one prior regimen.

FDA did not comment on the ODAC decision, but an agency spokesperson told MedPage Today in an email that the vote was 5-2.

In a prepared statement from drug developer Novartis, company officials said they believed the clinical trial evidence submitted to FDA had made a strong case for a favorable recommendation. Novartis Oncology president Bruno Strigini said the company will continue to work with FDA, which is not obligated to follow the ODAC decision.

A pan-HDAC inhibitor, panobinostat increases protein acetylation across multiple signaling pathways involved in oncogenesis. Preclinical studies demonstrated synergistic activity with the combination of panobinostat, bortezomib, and dexamethasone, and preliminary clinical studies provided evidence of durable responses in patients with relapsed or refractory myeloma treated with the combination.

Data reported at the 2014 American Society of Clinical Oncology meeting showed an improvement in progression-free survival (PFS) when patients with previously treated myeloma received the three-drug combination versus bortezomib, dexamethasone, and placebo. Though data remained immature at the time, Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston said the PFS benefit was on the order of 3 to 4 months.

In 2012 the European Union granted panobinostat orphan-drug status for treatment of myeloma.