U-M-developed treatment for Gaucher disease to be reviewed by FDA


Cerdelga, a treatment for Gaucher disease type 1 licensed by the University of Michigan to Genzyme Corp., recently was accepted for accelerated priority review by the FDA.

Cerdelga represents the first chemical entity conceived and developed at U-M. In a subsequent collaboration with Genzyme, preclinical studies were conducted, with the successful approval of the drug for clinical trials. It has already been under review by the European Medicines Agency.

Cerdelga offers an alternative to the approved Gaucher disease treatment — an intravenous enzyme replacement that costs roughly $250,000 a year per patient. Cerdelga is administered orally and could become a primary treatment for Gaucher type 1 disease.

Dr. James Shayman

The discovery leading to Cerdelga began 25 years ago when Dr. James Shayman, a nephrologist trained in lipid biology and cell biology, sat down next to the late Dr. Norman Radin, a U-M neurochemist who had developed a lead compound for blocking glycolipid synthesis that could potentially treat a group of rare and often deadly genetic diseases.

“It took only a few minutes for us to discover our shared scientific interests,” Shayman said.

Their collaboration continued until 1995 when Radin retired, but research continued by the Shayman group to design, synthesize and test glycolipid syntheses inhibitors. Following a series of “proof of concept studies” in experimental models of lysosomal storage diseases, these compounds were licensed to Genzyme in 2000 for clinical development.

Gaucher disease is an inherited disorder that affects many of the body’s organs and tissues. It affects more than 10,000 patients worldwide.

“With Gaucher disease, an enzyme deficiency leads to a buildup of fat in white blood cells in tissues. This leads to the massive enlargement of the spleen and liver, severe anemia, bleeding complications, and debilitating bone disease,” Shayman said. “Cerdelga appears to effectively reverse or prevent all of these complications.”

Collaborative work between Shayman and the Genzyme scientists led to the filing of an investigational new drug application with the FDA. Seven clinical trials followed including phase 3 trials conducted in 60 medical centers in 29 countries — comprising the largest group of clinical studies ever conducted on Gaucher disease and representing more than 500 patient years of exposure in over 400 individual patients.

The trials demonstrated that Cerdelga was a highly effective treatment method for newly diagnosed patients with Gaucher disease. It is a capsule taken twice daily that is easier to administer to patients than the infusions required by enzyme replacement therapies.

Genzyme, a Sanofi company, was granted a six-month priority review designation from the FDA on Dec. 11.

“The work of Dr. Shayman and Dr. Radin illustrates the societal benefits of transferring the discoveries from university research,” said Ken Nisbet, associate vice president of U-M Tech Transfer.  “Cerdelga promises to be a landmark therapy for patients worldwide afflicted with Gaucher disease, thanks to the work of our researchers and the significant investment of time, expertise, and resources by Genzyme.”

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