Seattle Genetics' (NASDAQ:SGEN) efforts to diversify beyond Adcetris look to have been dealt another blow with the revelation today that all trials of vadastuximab talirine, one of its key pipeline hopes, are being suspended.
Vadastuximab has been on a rollercoaster development path, its phase I study having only recently come off US clinical hold. With the end now virtually assured, Seattle's attention could turn to further deal-making while the group again falls back on Adcetris, whose first-line Echelon study is due to read out this year.
Indeed, vadastuximab's failure puts even more pressure on the outcome of Echelon. Success in this study could open up the front-line Hodgkin's lymphoma market for Seattle, helping turn Adcetris into a blockbuster by 2025 (Event - Seattle tries to move Adcetris into the upper Echelon, June 7, 2017).
However, the group has understandably been trying to diversify away from being an Adcetris one-trick pony by developing assets such as vadastuximab, an anti-CD33 antibody-drug conjugate that had been intended to treat the intractable hematological cancer acute myelogenous leukaemia and related conditions.
Today Seattle said vadastuximab's pivotal Cascade study had last week failed an independent review of unblinded data, which revealed an increase in deaths, including fatal infections, in subjects on vadastuximab versus those in the control arm. As a result, Cascade was being discontinued, and enrollment in the entirety of the project's clinical program suspended.
This comprises five separate trials, including one in myelodysplastic syndromes, that were aiming to recruit a combined 1,123 subjects.
Back in December things had been looking up for vadastuximab, with phase I AML data deemed strong enough to warrant highlighting at an Ash conference press briefing. Shortly afterwards, however, toxicity and deaths caused some clinical trials to be put on hold.
At the time this was thought not to be unduly serious, and analysts stressed that the pivotal Cascade study was unaffected; the hold was lifted in March, and Seattle planned to begin an additional phase II trial this year.
Thus today's move can be seen as an unexpected blow; Seattle stock opened down 11% today. In May another leg of the group's post-Adcetris plan was pulled away when its planned takeover of Immunomedics fell through.
While there still exists the possibility of vadastuximab development resuming, this must be seen as extremely unlikely.
It will be important to ascertain in detail the reasons for the increased deaths seen; while those in Cascade were said not to be related to hepatotoxicity, the December hold was prompted by six cases of liver toxicity and four deaths.
Problems might be due to broad expression of vadastuximab's target, CD33, lack of specificity for that antigen, vadastuximab's cytotoxic moiety, a problematic linker, other treatments given or patients' disease. EvaluatePharma consensus of sellside figures gives vadastuximab an NPV of $989m.
Seattle today cited the importance of the pipeline projects enfortumab vedotin and SGN-LIV1A in its post-Adcetris diversification plan. It cannot be denied, however, that the Immunomedics and vadastuximab setbacks have made it reliant on its core competency again.