A clinical trial by Seattle Genetics Inc. involving an experimental leukaemia cancer drug has been placed on hold after four patients died during the course of the trial. The U.S. Food and Drug Administration (FDA) has issued an order to halt or suspend enrolment in several studies being conducted by the company.

The drug, vadastuximab talirine, is an antibody-drug conjugate and is being tested to treat acute myeloid leukaemia. It is designed to target and destroy leukaemia cells while minimising the damage to healthy cells and had promising rates of inducing remissions in early-stage studies. Currently more than 300 patients have been treated with the drug.

Hepatotoxicity the cause of the deaths

Six patients in the trial suffered from hepatotoxicity, which resulted in the deaths of the four patients. The company is working with the FDA to determine if the drug caused the toxicity or the deaths. The clinical hold on these trials was imposed by the FDA so that it can evaluate the potential risk of hepatotoxicity to patients being treated with the drug and who underwent a stem cell transplant either before or after the treatment.

"This outcome does place risk on whether the program is able to continue," said Tony Butler, an analyst covering Seattle Genetics Inc. for Guggenheim Partners', an investment firm.

Butler further added that the toxicity is "most likely drug dependent" and that the company should consider changing the drug’s dosage or administration intervals to see if the effects differ.

However, stem cell transplantation is known to cause liver toxicity, noted Chad Messer, another analyst from Needham & Co's.

The drug is also being tested in patients with another form of blood cancer, myelodysplastic syndrome. The company has stated that it will not start any new trials of the drug while the FDA clinical hold is in place.

Currently one study has been stopped and two other studies have stopped new enrolment but trials that are ongoing, such as a late-stage, phase 3 trial, are proceeding.

Other deaths related to leukaemia trials

In July, the FDA placed a clinical hold on a trial conducted by Juno Therapeutics Inc. using an experimental treatment for a form of leukaemia after two patients died. The deaths came after the company added the chemotherapy drug, fludarabine to the treatment regimen and the FDA allowed the trial to resume after it was removed. However the company voluntarily suspended the trial again in November after two more patients died. They are currently evaluating the cause of deaths.

Pfizer also withdrew an antibody-drug conjugate from the U.S. market in 2010 after a study investigating their drug, gemtuzumab ozogamicin, showed a greater number of deaths among leukaemia patients taking the drug than those given chemotherapy. Gemtuzumab was also associated with veno-occlusive disease, a serious liver condition, which is also a factor in the liver damage reported by the Seattle Genetics Inc. studies. MIMS

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