03:43am Friday 28 February 2020

University of Michigan research leads to investigational treatment for Gaucher Disease


ANN ARBOR, Mich.  – Patients with Gaucher Disease saw significant improvement during Phase 3 clinical trials to investigate a therapy developed at the University of Michigan.

The results were announced this week by Genzyme, a Sanofi Company, which based the largest ever clinical program focused on Gaucher Disease on a concept created in U-M laboratories.

The oral compound eliglustat tartrate is capable of inhibiting the build-up of fatty substances in the cells of people with Gaucher Disease, an inherited condition that affects less than 10,000 people worldwide and, depending on the type, can lead to life-threatening damage to the spleen and liver and weaken bones.

The molecule for the new therapy was developed with U-M nephrologist James A. Shayman, M.D., former associate vice president for research at the University of Michigan, whose body of work in rare diseases may lead to convenient, less expensive patient treatments.

“Worldwide, there are about 4,000 to 5,000 patients currently treated for Gaucher disease with enzyme replacement therapy,” says Shayman. “We’ve taken a different approach, now termed synthesis inhibition therapy, by looking for ways to limit the build-up of these toxic materials in the first place.”

The concept of synthesis inhibition was first proposed 40 years ago by Norman Radin, Ph.D., emeritus professor at the University of Michigan Medical School.

Shayman studies lysosomal storage diseases, a group of 42 related disorders with one thing in common: Cells and body tissues are damaged by fatty substances that build up to toxic levels in lysosomes, which process cellular waste. For reasons scientists don’t understand, different types of these diseases attack different organs in the body.

Since 1988, Shayman, a professor of internal medicine and pharmacology, has been working on novel strategies to treat the defective enzyme problem in lysosomal storage diseases.  

Eliglustat tartrate, a novel glucosylceramide analog given orally, is designed to partially inhibit the enzyme glucosylceramide synthase, which results in reduced production of glucosylceramide. Glucosylceramide is the substance that builds up in the cells and tissues of people with Gaucher disease.

Patients treated with eliglustat tartrate had a statistically significant improvement in spleen size at nine months, compared with placebo. Spleen volumes in eliglustat tartrate treated patients decreased by 30 percent.

Patients also saw improvements in hemoglobin levels and platelet levels, as well as liver volumes compared with placebo-treated individuals.

The initial safety analysis from ENGAGE suggests that eliglustat tartrate was well tolerated. There were no serious adverse events reported in the primary analysis period and no clinically meaningful differences in the related adverse events reported between the two treatment groups.

Based on its mechanism of action, eliglustat tartrate may be a potential therapy for all patients, according to Genzyme.  Initiation of the Phase 2 and 3 studies of eliglustat tartrate in Gaucher disease followed an extensive pre-clinical research effort initiated at the U-M and which continued as a collaboration with Genzyme following a licensing agreement that started in 2000. 

“The efficacy and safety data from our ENGAGE trial are consistent with what were observed in our Phase 2 study, continuing to suggest that eliglustat tartrate is a potent, well tolerated oral compound that may become a meaningful option for patients and physicians,” said Genzyme President and Chief Executive Officer, David Meeker, M.D. “The development of eliglustat tartrate has been underway for more than a decade and is the largest clinical program ever focused on Gaucher disease, demonstrating our ongoing commitment to innovation on behalf of this community.”

Full results from the ENGAGE study are planned for presentation at the Lysosomal Disease Network World meeting, Feb. 12-15 in Orlando, Fla. Top-line data from Genzyme are second Phase 3 trial, ENCORE, are expected in early 2013.

The company is developing eliglustat tartrate, a capsule taken orally, to provide a convenient treatment alternative for patients with Gaucher disease type 1, and to provide a broader range of treatment options for patients and physicians to achieve individual therapeutic goals.

Currently, Genzyme’s Cerezyme,, the standard of care for patients with Gaucher disease type 1, is administered through intravenous infusions.

ENGAGE is a randomized, double-blind, placebo controlled study that evaluated the efficacy, safety and pharmacokinetics of twice-daily dosing of eliglustat tartrate in 40 patients untreated for at least six months.

Thirty-nine out of 40 study participants completed at least nine months of treatment.  At the end of nine months, patients who were on placebo were transitioned to eliglustat tartrate. After the primary analysis period concluded, all 39 patients chose to remain on treatment.

Eighteen medical centers in 12 countries in North America, South America, Europe, Asia and the Middle East are participating in this study.


Genzyme, a Sanofi Company



Kidney Disease at the University of Michigan


Share on:

Health news