The FDA has put a clinical hold or partial clinical hold on 3 clinical trials involving the orphan drug vadastuximab talirine (SGN-CD33A) in acute myeloid leukemia (AML) patients.
The holds were 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.
The developer of the drug—Seattle Genetics—stated that 6 patients have been identified with hepatotoxicity and 4 of them have died.
To date, a total of 300 patients have been treated with vadastuximab talirine in clinical trials.
In a press release
, Seattle Genetics stated it is working diligently with the FDA to determine whether there is any association between hepatotoxicity and treatment with vadastuximab talirine.
On Hold or Partial Hold
The clinical trials are hold or partial hold include:
The phase 1/2 trial
of vadastuximab talirine monotherapy in pre- and post-allogeneic transplant AML patients has been placed on full clinical hold.
Two phase 1 trials have been placed on partial clinical hold (no new enrollment, existing patients may continue treatment with re-consent). Ironically, they are titled as safety studies under clinicaltrials.gov—one involving AML patients
given vadastuximab talirine alone and in combination with a hypomethylating agent and one involving AML patients
given vadastuximab talirine alone and in combination with other standard treatments.
The phase 3 CASCADE
trial in older AML patients and phase 1/2 trial
in myelodysplastic syndrome—both involving vadastuximab talirine—are proceeding with enrollment.
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.