In December, the FDA had put a clinical hold
on Seattle Genetics’ 3 Phase 1 clinical trials involving the orphan drug vadastuximab talirine (SGN-CD33A) in acute myeloid leukemia (AML) patients for potential risk of hepatotoxicity. Three Months later, the FDA is allowing the company to resume the trials.
The hold was put in place to evaluate the potential risk of hepatotoxicity in patients who were treated with vadastuximab talirine and received allogeneic stem cell transplant either before or after treatment. Six patients had been identified with hepatotoxicity and 4 of them died.
The trials being resumed will assess vadastuximab talirine in 2 different settings. One trial is designed for the study of combination treatment with standard of care, or 7+3, chemotherapy in newly diagnosed younger AML patients. The second trial is designed to study the drug in monotherapy and combination treatment with hypomethylating agents in both newly diagnosed and relapsed AML patients.
The third trial, studying vadastuximab talirine monotherapy in pre- and post-allogeneic transplant AML patients will be discontinued by the company, given the challenges of developing therapies in this specific setting.
In a press release
, Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics said “The clinical hold on our early-stage vadastuximab talirine clinical trials has been resolved through a comprehensive analysis of the clinical data from over 300 patients treated to date, evaluation by an independent committee of clinical experts, collaborative interactions with the FDA, and protocol amendments designed to further enhance patient safety.”
Vadastuximab Talirine (SGN-CD33A)
Vadastuximab talirine (SGN-CD33A; 33A) is an antibody-drug conjugate targeted to CD33 which is expressed on most AML and MDS blast cells.
Acute Myeloid Leukemia (AML)
AML arises from the myeloid cells that serve as precursors to other types of blood cells. These cancer cells originate in the bone marrow and quickly spread through the bloodstream. The cancer cells crowd out normal blood cell cells, leading to reduced number of red blood cells, white blood cells, and platelets. This causes symptoms like fatigue, increased risk of infection, and bleeding.
Without treatment, the aggressive cancer progresses rapidly. Many patients receive intensive chemotherapy to kill the cancerous blood cells and a later stem cell transplant from a donor. Many patients respond to this initially, but relapse is common.
Younger patients do better with this therapy, but over half of patients with AML are over the age of 65. Many older people cannot tolerate the side effects of these intensive treatments. Drugs called hypomethylating agents (HMAs) provide the standard treatment for these patients, who typically do not survive longer than 10 months.