Liver Damage, Patient Deaths Lead FDA to Halt SeaGen Leukemia Trials

Xconomy Seattle — 

Seattle Genetics’ work to develop a drug to treat a form of leukemia has hit a roadblock following the deaths of four patients in clinical trials.

The FDA placed a clinical hold or partial holds on three early-stage trials evaluating the Bothell, WA-based company’s experimental drug vadastuximab talirine. Shares of SeaGen (NASDAQ: SGEN) tumbled more than 14 percent to $52.61 per share early Tuesday morning.

The deaths echo past work of other companies with similar types of drugs, known as antibody-drug conjugates, or ADCs. Despite more than three decades of development in the field, only SeaGen and Genentech have built businesses around an ADC product.

ADCs hitch powerful cancer-killing chemicals to antibodies, which are meant to deliver the toxic chemicals to the tumor for a direct hit, sparing healthy tissue and avoiding the debilitating side effects of chemotherapies and other cancer treatments.

SeaGen specializes in ADC technology and has brought one ADC to market, brentuximabvedotin (Adcetris), with its partner Takeda Pharmaceutical. But other than Adcetris and a product from Genentech, the field has had little success. Past efforts from other firms have gone awry because the powerful toxins also wreaked havoc in healthy tissues.

Leukemias are cancers of the bone marrow and blood cells. SeaGen is studying vadastuximab talirine in acute myeloid leukemia (AML), a form of the disease in which myeloid stem cells from bone marrow do not become healthy white blood cells.

Another ADC to treat AML came to market more than a decade ago, branded as Mylotarg, but was withdrawn by its maker, Pfizer (NYSE: PFE), after increased incidence of the liver condition, called veno-occlusive disease, whichSeaGen is now reporting in its trials.

To date, SeaGen says more than 300 patients have been treated with vadastuximab talirine in multiple clinical trials. But the company is now focusing on deadly liver damage that has apparently killed four patients in three early stage trials, in which patients received stem cell transplants before or after the treatment. Six patients overall have suffered liver-related side effects. SeaGen did not say how many were specifically veno-occlusive disease, only citing “several cases.” Veno-occlusive disease occurs when small veins transporting blood through the liver become blocked.

The FDA placed a clinical hold on the Phase 1/2 trial studying the SeaGen drug as a single therapy, which means all activity in the trial must halt.

Partial holds were placed on two Phase 1 trials also studying the SeaGen drug as a single therapy. These trials will not enroll new patients, but patients already in the trial may continue, as long as they consent. The Phase 1 trials include older patients who are receiving treatment with a separate drug that silences cancer genes and younger patients taking a course of chemotherapy, as well.

SeaGen said it is working with the FDA to determine the cause of the liver problems. The company added it won’t start any new studies with its drug until the FDA lifts all clinical holds.

But SeaGen said its other vadastuximab talirine trials already underway are continuing to enroll patients. Those studies are a Phase 3 study in older AML patients and a Phase 1/2 study in myelodysplastic syndrome, a disorder in which bone marrow does not produce enough healthy red blood cells. The company did not immediately respond to queries about why these trials were not halted.

Image of cells with acute myeloid leukemia by the National Cancer Institute.