Novartis AG's Panobinostat Fails To Win FDA Panel Support

Published: Nov 07, 2014

Novartis AG's Panobinostat Fails To Win FDA Panel Support

November 7, 2014

By Jessica Wilson, BioSpace.com Breaking News Staff

Basel, Switzerland-based Novartis announced yesterday that the U.S. Food and Drug Administration (FDA)'s Oncologic Drugs Advisory Committee (ODAC) voted not to recommend for approval the company’s investigational blood cancer compound LBH589 (panobinostat) in combination with Takeda Pharmaceuticals ’ Velcade (bortezomib) and the chemotherapy drug dexamethasone for patients with previously treated multiple myeloma.

The committee voted 5-2 against the recommendation for approval. While the FDA is not required to follow the advisory committee’s decision, the agency usually does.

According to documents released by the FDA before the vote, the question at hand was not whether the treatment was effective, but instead if its risks outweighed its benefits.

“Given [the] benefit:risk profile of the addition of panobinostat to bortezomib and dexamethasone, does the benefit outweigh the risks for patients with relapsed multiple myeloma?” wrote the panel.

To make its decision, the committee reviewed results from a Phase III randomized, double-blind, placebo-controlled multicenter global trial called PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA) and a Phase II US multicenter, single-arm, open-label study called PANORAMA-2. The trials did show that the panobinostat combo treatment improved progression-free survival (PFS) by 3.9 months compared to bortezomib and dexamethasone alone.

The Pharma Times noted, however, that an “independent FDA review assessed improved PFS at 2.2 months with panobinostat.”

A major issue, as well, was the higher death rate due to reasons unrelated to cancer progression in patients receiving the panobinostat in combination with bortezomib and dexamethasone as opposed to the patients who received only bortezomib and dexamethasone.

A document released by the FDA prior to the advisory committee meeting notes that that there was “an increased incidence of deaths not due to progressive disease (7 percent vs. 3.5 percent)” in patients who received the treatment combination with panobinostat vs. those that did not.

Additional side effects that caused concern included, myelosuppression, haemorrhage, infection, gastrointestinal toxicity and cardiac toxicity.

Not surprisingly, Novartis was not pleased with the decision. “We are disappointed by this voting outcome and believe the results from our clinical trials provide strong evidence to support LBH589 as a potential first-in-class treatment option for multiple myeloma, a cancer where an unmet patient need exists,” Bruno Strigini, president of Novartis Oncology, was quoted as saying in a statement. “We will continue to work with the FDA as it completes its review of the US application.”

Panobinostat, or LBH589, is a pan-deacetylase (pan-DAC) inhibitor, part of a class of anticancer agents known generally as histone deacetylase (HDAC) inhibitors or HDIs. Historically, HDIs have been used as mood stabilizers and anti-epileptic drugs and have only recently begun to be investigated as possible treatments for cancer.

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