Shares in Seattle Genetics were down 15% today after it announced the FDA had slapped both partial and full clinical holds on several of its early-stage trials for vadastuximab talirine (aka SGN-CD33A) in blood cancer after four deaths and serious adverse events.
Specifically, the U.S. regulator said that a phase 1/2 trial of the med on its own, both in pre- and postallogeneic transplant acute myeloid leukemia (AML) patients “has been placed on full clinical hold,” according to its statement.
On top of this, two phase 1 studies have been hit with a partial clinical hold (i.e., no new enrollment, but existing patients may continue treatment with re-consent).
These studies were looking at the med on its own and include a subset of older AML patients in combination with hypomethylating agents, as well as a combo treatment with chemo in newly diagnosed, younger AML patients.
“No new studies will be initiated until the clinical holds are lifted,” the biotech said.
The company said that its phase 3 ‘Cascade’ trial in older AML patients, and phase 1/2 trial in myelodysplastic syndrome, “are proceeding with enrollment.”
What happened? Well, the biotech reported that six patients have been identified with liver damage, and most damaging of all, there were four deaths.
“Seattle Genetics is working diligently with the FDA to determine whether there is any association between hepatotoxicity and treatment with SGN-CD33A, to promptly identify appropriate protocol amendments for patient safety and to enable continuation of these trials,” the biotech said.
Analysts at Leerink remained fairly positive despite the setback, saying, “While the FDA hold incrementally increases the developmental risk of SGN-CD33A, we note that in the indications evaluated the affected trials only contribute 5% to our 2025E revenue forecast for Seattle.
“We spoke with management, who expects a potential rapid resolution of the partial clinical hold on two of the affected phase 1/2 trials in AML, while the FDA seems predominantly focused on the ongoing pre-transplant conditioning study where the rate of hepatotoxicity is already high with standard of care chemotherapy alone," they added.
The analysis explained that along with graft versus host disease and cytomegalovirus infection, veno-occlusive disease “is one of the most frequently encountered serious complications after stem cell transplantation.”
The company’s ADC tech, which drives vadastuximab talirine, has attracted partnerships and tie-ups with the likes of AbbVie, Astellas, Bayer, Celldex, Genentech, GlaxoSmithKline and Pfizer.
It was riding high earlier this month when its antibody-drug conjugate SGN-LIV1A showed efficacy in patients with triple-negative metastatic breast cancer—a particularly hard-to-treat patient population—in a phase 1 trial presented at the San Antonio Breast Cancer Symposium.
Seattle Genetics is best known for Adcetris (brentuximab vedotin), which reached the market as a second-line therapy for classical Hodgkin lymphoma around five years ago.