- Seattle Genetics is shutting down clinical investigations for one of its leading pipeline drugs, citing safety concerns related to a late-stage trial.
- An independent data monitoring committee with access to unblinded information from the Phase 3 CASCADE study found that acute myeloid leukemia (AML) patients receiving Seattle Genetics' vadastuximab talirine demonstrated higher rates of death than those in the control arm, according to a June 19 statement.
- In response, the West Coast drugmaker is halting enrollment and dosing for all studies of vadastuximab talirine, which include CASCADE, a couple early-stage trials also in AML and a Phase 1/2 trial testing the drug in participants with myelodysplastic syndrome (MDS).
Editor's Note: On June 20, Seattle Genetics submitted an sBLA for Adcetris in the cutaneous T-cell lymphoma indication.
It's been somewhat of a rollercoaster 2017 for Seattle Genetics. The company hit a peak in mid-February, announcing a deal worth up to $2 billion that would give it access to an antibody drug conjugate from Immunomedics. Shortly after, however, an Immunomedics activist investor launched a campaign to prevent the sale, and ultimately succeeded.
Seattle Genetics experienced another high a few months later when the Food and Drug Administration decided to lift partial holds on two early-stage studies of vadastuximab talirine in AML. The holds were due to four hepatotoxicity-related patient deaths in a separate, Phase 1/2 trial that the company ended up scrapping.
Now, the drugmaker is yet again experiencing a fall. Its stock closed at $61.88 per share on Monday on news of the safety issues, down 4% from Friday.
"This is a disappointing and unexpected result for the CASCADE trial," Seattle Genetics CEO Clay Siegall said in the June 19 statement. "Patient safety is our highest priority, and we will closely review the data and evaluate next steps."
Importantly, Seattle Genetics also noted the deaths in CASCADE included fatal infections, but overall safety concerns "do not appear related to hepatotoxicity."
With vadastuximab talirine sidelined, eyes are turning to the company's only marketed product, Adcetris (brentuximab vedotin). The drug first gained U.S. approval in 2011 as a treatment for Hodgkin and anaplastic large cell lymphomas, and is currently in a Phase 3 study testing it in combination with doxorubicin, vinblastine, and dacarbazine in patients with advanced classical Hodgkin lymphoma.
Additionally, Seattle Genetics plans to submit to the FDA in mid-2017 a supplemental Biologics License Applicaiton (sBLA) indicating Adcetris for the treatment of CD30-positive cutaneous t-cell lymphoma.
Label expansions would surely help market Adcetris, which has a black box warning for a serious brain infection called progressive multifocal leukoencephalopathy. The drug is on an upswing, though, bringing in $70.3 million worth of net sales during the first quarter, up 20% from the same period in 2016.
"The increase in sales volume in 2017 was primarily driven by increased use of ADCETRIS across multiple lines of therapy in Hodgkin lymphoma and for the treatment of other CD30-expressing malignancies," Seattle Genetics said in its most recent 10-Q filing with the Securities and Exchange Commission.