An experimental blood cancer drug shelved for safety concerns is being brought back to clinical development.
San Diego startup Impact Biomedicines said Friday it has raised $22.5 million from the venture capital firm Medixci to help get the drug to market. Called fedratinib, the drug treats the bone marrow cancers polycythemia vera and myleofibrosis.
B y 2013, fedratinib had reached advanced clinical testing and prospects for approval looked bright. But reports of a dangerous form of brain swelling called Wernicke’s encephalopathy caused the U.S. Food and Drug Administration put a hold on further development. Then Sanofi dropped the program.
However, a number of patients responded to fedratinib who didn’t receive the same benefit from alternatives, said Dr. Catriona Jamieson, a UC San Diego Moores Cancer Center physician/researcher who treated patients with the drug.
One of those patients was Theresa Blanda, whose cancer regressed after Jamieson treated her with fedratinib. When the drug became unavailable, she relapsed and then rallied with another experimental drug, pacritinib.
But the relief was short-lived.
Blanda died last year, although she lived long enough to get back in touch with her former high school sweetheart and start thinking of marriage.
Up until her death, Blanda continued fighting the disease, although her appeals to get a new supply of fedratinib went unanswered.
“It was her reaching out and Catriona pushing me that led to the genesis of this company,” Hood said. “There were a number of patients like Theresa who had long, durable responses.”
At the time Sanofi dropped the drug, it appeared likely that several other experimental drugs in its class would be at least as effective, Jamieson said. But they turned out to be less powerful.
And Jamieson said researchers have since discovered why the patients developed Wernicke’s encephalopathy, a result of vitamin B1 deficiency. It can develop in cancer patients who are inadequately nourished because of the stress of the disease.
This effect wasn’t noticed before because researchers weren’t looking for it, Jamieson said.
Now that the safety issue has been addressed, the FDA has dropped the hold. It may be possible to file for FDA approval without any further testing, Hood said. Sanofi had already completed Phase 3 testing of fedratinib with favorable results.
“In 2013, this drug had completed all the work necessary to file an NDA (New Drug Application),” Hood said. “The hold was placed on a Friday, and they terminated the program the following Monday.”
Fedratinib inhibits an enzyme called JAK2 kinase. The cells it targets are cancer stem cells, cancer cells that activate some of the same genetic mechanisms at work in stem cells. Jamieson received funding for her work from sources including the California Institute for Regenerative Medicine, the state’s stem cell agency.
The drug was originally developed by San Diego-based TargeGen, which Sanofi purchased in 2010 for up to $635 million. After Sanofi abandoned the drug, Hood, who was TargeGen director of medical research, worked for years to get testing back on track.
Hood had to do three things: Acquire the rights to fedratinib from Sanofi, raise enough money to complete development, and convince the FDA to release its hold.
With all three accomplished, Hood is asking the FDA whether Impact can file for approval, or whether more testing is needed first.
“It’s an open negotiation right now with the FDA,” he said.