Matthew Ros, chief strategy and business officer for Epizyme Inc., said the company is “not providing specific guidance at the moment” about the sales force that will be deployed to market Tazverik (tazemetostat) in follicular lymphoma (FL), an indication for which U.S. regulators are considering the oral, first-in-class EZH2 inhibitor. “But I can assure you we’ve planned very thoughtfully” about the effort, he said. “That's always been a part of why we thought epithelioid sarcoma [ES] was such a strategically important component of the overall business strategy to get on-the-ground experience.” The sales force numbers 19 for now.
As expected and on its assigned PDUFA date, Cambridge, Mass.-based Epizyme won accelerated FDA clearance for Tazverik in ES patients not eligible for curative surgery. The nod came as little surprise after December’s decision by members of the FDA’s Oncologic Drugs Advisory Committee (ODAC), which voted unanimously to recommend approval of the compound in ES, an aggressive soft-tissue cancer with a bleak prognosis that strikes about 120 patients in the U.S. per year.
Epizyme’s NDA submission was based mainly on data from the 62-patient epithelioid sarcoma cohort from its phase II study of Tazverik. The results, reported in June at the 2019 American Society of Clinical Oncology annual meeting in Chicago, showed that tazemetostat treatment resulted in clinically meaningful and durable responses, and was generally well-tolerated.
The company intends full approval in ES to be supported by a 1-to-1 randomized, controlled clinical trial in the front-line treatment setting comparing Tazverik in combination with doxorubicin vs. placebo plus doxorubicin in about 150 patients. With progression-free survival as the primary efficacy endpoint, the trial includes secondary goals of overall survival, disease control rate, overall response rate and duration of response.
Epizyme also will conduct postmarketing activities, including clinical pharmacology evaluations to assess the effect of the drug on liver function and the effect of CYP3A inhibitors and inducers on Tazverik to inform aspects of the prescribing information. The company will expand enrollment in the sixth cohort of its phase II study, too, which has enrolled 44 patients so far, for a total of at least 60. That expansion is meant to provide more patient experience details for potential future inclusion in the label.
Also in December, Epizyme submitted an NDA for accelerated approval of tazemetostat for relapsed or refractory FL patients, with or without EZH2 activating mutations, who have received at least two prior lines of systemic therapy. In a report at the time, Jefferies analyst Michael Yee approved of “getting the ball rolling on the larger and more important $500 million-plus indication. For FL, we estimate the PDUFA could be August, but acknowledge it could be approved earlier, given the shared modules/components from the ES filing” and the likely go-ahead in ES – where the ODAC vote surprised Yee, who noted that it came despite “cautious commentary from the FDA review documents and concerns about an open-label single-arm study.”
FL is typically a slow-growing or indolent form of non-Hodgkin lymphoma (NHL) that arises from B-lymphocytes, and accounts for 20% to 30% of NHL cases. It’s “usually not considered to be curable, but more of a chronic disease,” according to the Lymphoma Research Foundation. “Patients can live for many years with this form of lymphoma.”
‘Year of de-risking,’ buyout ahead?
SVB Leerink analyst Andrew Berens said in a report that “some investors may be disappointed” at the price tag on Tazverik in ES. Epizyme set a wholesale acquisition cost (WAC) of $15,500 per month, which equates to $186,000 annually. Company backers might have “assumed the company could price at a premium level in this ultra-rare disease,” in the vein of Cambridge, Mass.-based Blueprint Medicines Corp., which put the WAC for Ayvakit (avapritinib) at $32,000 per month.
Shares of Epizyme (NASDAQ:EPZM) closed at $22.40, down $4.32, or 16%.
Ayvakit, a KIT and PDGFR alpha inhibitor, was approved for gastrointestinal stromal tumors. Epizyme did broadcast its ballpark WAC intentions earlier, though, saying Wall Street should expect pricing between that of PI3K inhibitors and Revlimid (lenalidomide, Celgene Corp.), or roughly $11,000 to $16,000. “Moving forward, we believe Tazverik could gain an earlier-than-expected approval for FL, given that some of the modules in the NDA package (i.e., non-clinical [elements], chemistry manufacturing and controls modules, etc.) have already been validated by the ES approval,” Berens wrote, echoing Yee.
CEO Robert Bazemore said during a conference call with investors that groundwork has been laid in ES. “We understood that from the time we had the data available in our phase II study until we got through this that there would be patients who would need access to the drug, so we've had an ongoing early access program, and we've had some patients enroll in that,” he said. “Our expectation is those patients would be converted over to commercial supply through their managed-care payers. At the same time, medical science liaisons have been out in the field identifying physicians in these centers, helping them understand what patients might be in their practices – which ones of them might be appropriate for therapy or for change of therapy. I would say that physicians are ready” to make such decisions.
Yee called 2020 “the year of de-risking” for Epizyme. “The bottom line bull thesis is that Epizyme could see two FDA approvals this year in ES and FL, in total addressing a potential $1 billion market and putting Epizyme into a scarce bucket of ‘approved companies.’” He added that “longer-term models may underappreciate the peak sales of $1 billion or greater, due to the idea of ‘maintenance’ therapy, where [the company is] running a second-line, randomized FL study, so this [product] could end up being more Revlimid-like than Street appreciates.”
He views Epizyme as a potential takeover candidate, “given lots of companies interested in these types of commercial oncology assets as easy tuck-ins” for U.S., EU and Japanese concerns.