FDA’s in-house review offers bleak assessment of Epizyme’s tazemetostat — but win or lose this cancer drug may still have a future
Epizyme will have to overcome a tough assessment from the FDA’s in-house review team for their cancer drug tazemetostat if they expect to make it to the market with an OK on epithelioid sarcoma. But they $EPZM may well have the agency’s oncology panel on their side, where there’s a built-in bias in favor of even marginal new drugs when it comes to offering physicians and patients another drug to choose from.
As the FDA notes, there’s not much data to support tazemetostat as an effective drug for these cases of sarcoma. Pooling data from 2 cohorts in their pivotal study, they came out with a collective overall response rate of only 13%. Out of 106 patients, only 2 experienced a complete response.
The expert panel has to compare that potential benefit with a litany of risks. Close to half the patients experienced a grade 3 or 4 serious adverse event. And there was this:
A total of 23 (37%) patients had a serious AE (SAE). SAEs that occurred in ≥ 2 patients were hemorrhage and pleural effusion (6.5%), dyspnea (5%), and cellulitis and pain (3.2%). There were no fatal adverse events attributable to tazemetostat. Although 34% of patients required a dose interruption for toxicity, dose reductions and discontinuations of tazemetostat for toxicity were rare.
Also unhelpful is tazemetostat’s checkered past. The biotech had a rough go last year when the FDA put trial recruitment on hold after a young patient developed secondary T-cell lymphoma. And that followed their decision to scrap a separate program for diffuse large B-cell lymphoma, DLBCL, after concluding that it wouldn’t succeed as a monotherapy.
Jefferies’ Michael Yee read the agency review and concluded that Epizyme had at best a 20% or 25% chance of an approval, noting the FDA’s hesitancy to call it on the risk/reward ration.
(W)e could see FDA asking EPZM to run a randomized study, especially as LLY’s Lartuvo was recently pulled after the drug failed its confirmatory study in soft tissue carcinoma, (4) while Taz appears well tolerated, the risk of secondary malignancies remains unclear (e.g. T-LBL) and that could be an “on-target” effect of Taz (this was the premise of the partial clinical hold in 2018). However, we note in the ODAC division, the FDA is generally more lenient because there are no approved therapies, so FDA could still approve Taz despite voicing cautiousness.
For Yee, though, this is a bit of a sideshow. The real upside for Epizyme is the larger follicular lymphoma field, where the biotech stands to make a potential $500 million-plus in peak sales. So whatever happens during the panel review tomorrow, he’ll still be holding out hope for something bigger ahead.
