Fatalities put Seattle Genetics’ trials on hold

Three out of five clinical trials evaluating Seattle Genetics’ investigational ADC vadastuximab have ground to a halt after six adverse events and four fatalities were reported. No such toxicity has been reported in trials involving newly-diagnosed patients.

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Seattle Genetics abruptly ended the holiday vibes on Tuesday with news that the FDA had placed several clinical trials for its investigational drug vadastuximab talirine on hold, following six severe adverse events and four fatalities.

The deaths occurred in a Phase 1/2 trial of vadastuximab in relapsed acute myeloid leukemia (AML). Notably, these patients also received an allogeneic stem cell transplant, either before or after treatment.

Shares were down 14.6 percent in premarket trading, but Needham & Company Analyst Chad Messer urged investors not to overreact:

“The hold stems from concerns for potential liver toxicity in patients that receive stem cell transplants before or after treatment. While we expect shares to trade down this morning, we caution investors not to overreact as liver toxicity is a known side effect of stem cell transplantation.”

Four clinical trials are underway for vadastuximab in AML. Three of these are geared towards newly-diagnosed patients and have reported low toxicity.

But something went horribly wrong in the fourth trial, which aimed to treat relapsed AML in a mixed group of pre- or post-transplant patients. It is unclear at this point whether the adverse events were caused or worsened by Seattle Genetics’ therapy.

The company reported that six patients in the trial were diagnosed with hepatotoxicity, including several cases of veno-occlusive disease (VOD), with four fatal events.

Also known as hepatic sinusoidal obstruction syndrome (SOS), VOD most frequently occurs in patients undergoing types of hematopoietic cell transplantation (HCT), such as those that occurred 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 progressing well.

In early December Seattle Genetics delivered positive results at the American Society of Hematology meeting in San Diego. Among the updates was data from a Phase 1b study evaluating vadastuximab, in combination with the frontline standard of 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 show a high rate of remissions in younger newly diagnosed AML patients without significantly adding to the toxicity of the treatment.”

Two other ongoing trials of vadastuximab will continue enrollment. These include the Phase 3 CASCADE trial of approximately 500 older, previously untreated 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 expressed on the white blood cells of nearly all AML patients.

It is the second most advanced compound in Seattle Genetics’ ADC pipeline. The lead compound Adcetris was approved in 2011.

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