4 Fatal Deaths in Seattle Genetics' Early-Stage Trials of AML Drug
December 27, 2016
By Alex Keown, BioSpace.com Breaking News Staff
Bothell, Wash. – Seattle Genetics announced today that the U.S. Food and Drug Administration (FDA) has placed a clinical hold or partial clinical hold on several of its early-stage clinical trials of vadastuximab talirine (SGN-CD33A) in acute myeloid leukemia (AML).
Six patients were shown to have hepatotoxicity, including several cases of veno-occlusive disease, with four deaths. The company is working with the FDA to determine if the hepatotoxicity and deaths are related to SGN-CD33A.
The Phase I/II trial of the drug as a monotherapy in pre- and post-allogeneic transplants AML patients received the full clinical hold. Two additional Phase I trials have received partial holds, which means that there is no new enrollment, but patients already on the trial can continue if they provide consent again. Of the two Phase I trials, one is a monotherapy that includes a subset of older AML patients in combination with hypomethylating agents. The other is a combination treat with 7+3 chemotherapy and SGN-CD33A in newly diagnosed younger AML patients.
Seattle Genetics has two other ongoing trials of SGN-CD33A, a Phase III CASCADE trial in older AML patients, and a Phase I/II trial in myelodysplastic syndrome, that are continuing to enroll patients.
CD33A targets CD33, which is expressed on the blast cells in AML and MDS. An antibody-drug conjugate (ADC), it is designed to be stable in the bloodstream. As the company describes, “The CD33 engineered cysteine antibody is stably linked to a highly potent DNA binding agent called a pyrrolobenzodiazepine (PBD) dimer via site-specific conjugation technology (EC-mAb). PBD dimers are significantly more potent than systemic chemotherapeutic drugs and the EC-mAb technology allows uniform drug-loading onto an ADC.”
The FDA and the European Commission granted the drug Orphan Drug Designation for AML.
Seattle Genetics took a hard hit at the news. Shares traded on November 17 for $73.71, and were headed downward to $61.43 on Friday, December 23. Shares are currently trading for $53.52.
Earlier this month, Seattle Genetics presented data from an ongoing Phase I trial of SGN-LIV1A in patients with metastatic breast cancer (MBC), with a particular focus on triple-negative MBC (TN MBC). The presentation was at the 39th San Antonio Breast Cancer Symposium. The data looked at 53 patients with LIV-1-expressing MBC treated with the SGN-LIV1A monotherapy. Of the 30 of 47 efficacy-evaluable patients with TN MBC, 37 percent (11) had a partial response (PR). The disease control rate (DCR) was 67 percent and the clinical benefit rate (CBR) was 47 percent.
“The data presented as SABCS on SGN-LIV1A demonstrate promising early antitumor activity with a 37 percent partial response rate in patients with triple negative metastatic breast cancer, for which there are no available targeted treatments,” said Jonathan Drachman, the company’s chief medical officer and executive vice president, Research and Development, in a statement at the time. “We are enrolling additional patients with triple negative metastatic breast cancer in our Phase I study to optimize the dose and inform the next steps for development of SGN-LIV1A in this population with high unmet need.”