Future bleak for Novartis’ myeloma drug
pharmafile | November 21, 2014 | News story | Medical Communications | FDA, Farydak, Novartis, ixazomib, myeloma, panobinostat
Novartis suffered a major disappointment with the negative FDA panel vote for multiple myeloma candidate Farydak earlier this month, but further testing could resurrect the drug, says an analyst.
The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 5-2 against approval of Farydak (panobinostat) – a pan-deacetylase (pan-DAC) inhibitor – as a combination therapy with Takeda’s Velcade (bortezomib) and dexamethasone in previously-treated patients with multiple myeloma.
Committee members described the decision as ‘difficult’ but concluded that the trial submitted in favour of approval (PANORAMA-1) did not show conclusively that the benefits of the drug outweighed its risks.
Specifically, the trial found that 7% of patients treated with panobinostat arm died from non-cancer complications, compared to just 3.5% in the comparator arm. Reported side effects included myelosuppression, bleeding, infection, gastrointestinal toxicity and cardiac toxicity.
Novartis submitted panobinostat for approval in early 2014 and in May was granted a priority review designation by the FDA, with a verdict due this month.
The FDA does not have to follow the ODAC recommendation, but rarely makes the opposite decision. A drug with a similar mode of action – Merck & Co’s histone deacetylase (HDAC) inhibitor Zolinza (vorinostat) – also failed to show much benefit when combined with Velcade in multiple myeloma.
The disease is a progressive haematologic cancer that comes from bone marrow and remains incurable, with a five-year survival rate of around 45 per cent.
“Alongside inconsistent data regarding progression-free survival, no statistically-significant overall survival benefit for panobinostat was determined by either the Novartis or the FDA analysis,” says GlobalData analyst Jamie Mallinson.
However, there could still be a place for panobinostat, “provided that Novartis reconsiders the dosing strategies that will be used in future trials,” he adds, suggesting that some clinicians believe this will improve the drug’s toxicity profile.
There is a real need for drugs with new mechanisms of action, said Mallinson, although the development of such agents is always ‘fraught with risk’.
The problems facing panobinostat are creating opportunities for other drugs coming through the pipeline for multiple myeloma, including monoclonal antibodies (mAbs) such as Janssen/Genmab’s CD38-targeting daratumumab and the anti-CS1 antibody elotuzumab from Bristol-Myers Squibb/AbbVie and new proteasome inhibitors like Takeda’s ixazomib (MLN9708).
“The question now is whether Novartis will continue to pursue panobinostat’s development to maintain its lead over potential competitors in the rapidly-evolving multiple myeloma treatment market, concludes Mallinson.
Phil Taylor
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