- Seattle Genetics' hopes to expand the market opportunity for its flagship blood cancer drug Adcetris (brentuximab vedotin) got a lift Monday, with the Bothell, Washington-based biotech announcing positive results from a Phase 3 study in frontline advanced Hodgkin lymphoma.
- Treatment with Adcetris plus combination chemotherapy improved modified progression-free survival over a commonly used four-drug chemo cocktail, reducing the risk of disease worsening or death by 23%.
- But new safety concerns and the moderate level of improvement seen over control treatment appeared to dampen investor enthusiasm, pushing shares in Seattle Genetics down 11% in Monday trading. Shares had already taken a hit earlier this month when the company announced it would halt further development of a leading pipeline candidate.
Seattle Genetics' ECHELON-1 study pitted Adcetris combined with three chemo drugs (adriamycin, vinblastine, dacarbazine or AVD) against the current standard of care for classical Hodgkin lymphoma patients (AVD plus bleomycin) in over 1,300 patients.
At two years, 82.1% of patients in the Adcetris arm had not seen their cancer progress versus 77.2% in the control arm as measured by modified progression-free survival (PFS), a measure that counts treatment with an additional drug after an initial, incomplete response as an event.
While the difference is not dramatic, improving on standard of care in the frontline setting is still an advance. Adcetris plus AVD also eliminates belomycin, which can be highly toxic and lead to lung-scarring.
Seattle Genetics did report, however, increased incidence of febrile neutropenia and peripheral neuropathy in the treatment arm of ECHELON-1. Use of prophylatic growth factors reduced the febrile neutropenia in some patients, while dose modifications helped manage the peripheral neuropathy.
Securing approval in first-line treatment of advanced classical Hodgkin lymphoma would significantly expand the market for Adcetris and would be an important catalyst for company revenues, which are almost wholly dependent on Adcetris direct sales or royalties from Seattle Genetics' partner Takeda.
Seattle Genetics and Takeda share development costs for Adcetris equally, while Seattle Genetics has commercialization rights in the U.S. and Canada.
The two companies said Monday they plan to submit the results from the ECHELON-1 study to regulatory authorities in their respective territories, but did not specify a target timeline.
Seattle Genetics is also working to broaden Adcetris' label based on positive results from a Phase 3 study and two Phase 2 investigator-led trials in cutaneous T-cell lymphoma (CTCL), a type of non-Hodgkin lymphoma that primarily involves the skin.
There are about 2,000 patients who get systemic therapy annually in the U.S. for CTCL, half of whom express the CD30 marker that Adcetris targets, according to company estimates. The biotech, which filed a supplemental Biologics License Application to the FDA earlier this month, hopes to win a broad label across different subtypes of CTCL.
Sales of Adcetris totaled just over $70 million in the first quarter, up 20% from the same period a year ago. Seattle Genetics expects annual revenues from the drug to reach between $280 million and $300 million, with royalties from Takeda on international sales kicking in another $50 to $55 million.
Approval of both Bristol-Myers Squibb's Opdivo (nivolumab) and Merck's Keytruda (pembrolizumab) for patients with heavily pretreated classical Hodgkin lymphoma could eventually mean new competition for Adcetris in the post stem cell transplant or relapsed settings.
But so far, Seattle Genetics isn't seeing a threat.
"Despite the recent FDA approval of a second PD-1 inhibitor in relapsed Hodgkin lymphoma setting, we have seen no erosion in share in our existing relapsed [Hodgkin lympoma] business," said Darren Cline, head of commercial at Seattle Genetics, on an April 27 earnings call.
"Most prescribers have indicated they view the checkpoint inhibitor agents as interchangeable and would use both in post-Adcetris later lines of therapy or palliative setting if necessary."
Seattle Genetics has also partnered with Bristol-Myers directly to test Adcetris combined with Opdivo in relapsed Hodgkin lymphoma.