Seattle Genetics abruptly ended the holiday vibes on Tuesday with news that the FDA had positioned several clinical trials for its investigational drug vadastuximab talirine on hold, following six severe adverse events plus four fatalities.
The deaths occurred in the Phase 1/2 trial of vadastuximab in relapsed severe myeloid leukemia (AML). Notably, these patients also obtained an allogeneic stem cell transplant, either before or even after treatment.
Shares were down fourteen. 6 percent in premarket trading, but Needham & Company Analyst Chad Messer urged investors not to overreact:
“ The hold comes from concerns for potential liver toxicity in patients that will receive stem cell transplants before or after therapy. While we expect shares to trade down today, we caution investors not to overreact as liver degree of toxicity is a known side effect of stem cell transplantation. ”
Four clinical trials are underway for vadastuximab in AML. Three of these are aimed at newly-diagnosed patients and have reported low toxicity.
But something went horribly wrong in the fourth demo, which aimed to treat relapsed AML in a mixed number of pre- or post-transplant patients. It is unclear at this time whether the adverse events were caused or worsened simply by Seattle Genetics’ therapy.
The company reported that will six patients in the trial were diagnosed with hepatotoxicity, which includes several cases of veno-occlusive disease (VOD), with 4 fatal events.
Also known as hepatic sinusoidal blockage syndrome (SOS), VOD most frequently occurs in patients going through types of hematopoietic cell transplantation (HCT), such as those that happened in patients in the fatal trial.
According to the company news release, over 300 patients have been dosed with the compound. And until now, the drug was advancing well.
In early December Seattle Genetics shipped positive results at the American Society of Hematology meeting within San Diego. Among the updates was data from a Phase 1b study evaluating vadastuximab, in combination with the frontline standard associated with care, for younger patients with newly diagnosed AML. According to the Dec. 3 news release, the drug was well-tolerated.
“ The phase 1 results of 33A [vadastuximab] in combination with standard of care display a high rate of remissions in younger newly identified AML patients without significantly adding to the toxicity from the treatment. ”
Two other ongoing studies of vadastuximab will continue enrollment. These include the Stage 3 CASCADE trial of approximately 500 older, previously without treatment AML patients and the Phase 1/2 trial in myelodysplastic syndrome (MDS).
Vadastuximab is an investigational antibody-drug conjugate (ADC) that targets CD33, a protein portrayed on the white blood cells of nearly all AML patients.
It is the second most advanced compound within Seattle Genetics’ ADC pipeline. The lead compound Adcetris was approved in 2011.
Photo: devon, Big Stock