National Foundation for Ectodermal Dysplasias

EDI200: Replacement Therapy Gives Hope for Successful Treatment of HED Symptoms

Future generations of families affected by X-linked hypohidrotic ectodermal dysplasia (XLHED) may have an option of a treatment that would eliminate the symptoms of the condition. The National Foundation for Ectodermal Dysplasia is thrilled to be working with Edimer Pharmaceuticals, Inc. whose vision is to deliver a significant and durable improvement in the health and quality of life to future generations affected by the rare genetic disorder, XLHED.

“It is incredibly exciting to think that the HED gene was only discovered 13 years ago in 1996 and we are already talking about a treatment that could eradicate the effects of the condition,” Richter said. “I am excited that future generations of NFED families may have this treatment option and proud that NFED has helped make it possible.”

The news was announced at the NFED National Family Conference last July. Dr. Neil Kirby, CEO of Edimer Pharmaceuticals, announced that his newly formed company was moving forward with the development of a recombinant protein (EDI200; formerly called APO200) as a potential therapy for XLHED.

Edimer’s goal is begin clinical trials in 2011. Treatment would mean giving infant males affected by XLHED a short course of injections of the EDI200 protein shortly after birth. Eventually, the project will include female carriers of XLHED. While there were no negative side effects of the therapy when used in the HED mice and dogs research, the side effects and efficacy in humans are still unknown.

History
The road to identify and understand the gene that causes XLHED and to develop treatment therapies has been a relatively short one in the world of science. The NFED began supporting Dr. Jon Zonana’s research on HED at Oregon Health Sciences University in 1991 with funding and access to patients. In 1996, his laboratory collaborated with a team of international researchers to identify the first gene responsible for HED. It was located on the X chromosome and resulted in the most common form of the condition. They then were able to identify three more genes involved in the development of HED. Locating the genes helped researchers understand the workings of HED and provided a drug target for scientists.

By 2003, Dr. Pascal Schneider and Dr. Olivier Gaide at the University of Lausanne characterized a protein implicated in HED called ectodysplasin A or EDA. They designed a lead drug candidate, which we now call EDI200. It is a “fusion protein” which combines a portion of the EDA1 protein (which, in XLHED patients, is not produced correctly) with a portion of an antibody molecule. Drs. Scheider and Gaide successfully tested EDI200 in a mouse model of XLHED as a therapy in conditions where the naturally produced EDA1 molecule is missing in these models. Using the dog as a model for human disease, Dr. Margret Casal at the University of Pennsylvania examined the treatment of XLHED using the same therapy. In both studies, by injecting the missing protein back, the mice and dogs developed normal teeth, sweat glands and hair.

A company in Switzerland called Apoxis licensed the drug from the University of Lausanne, and in 2007 was acquired by a Danish company, TopoTarget, which was primarily interested in other Apoxis products. Essentially, the research stalled at this point. Christophe Maier and Stephane Demotz, originally from Apoxis, formed Edimer Biotech SA in 2008 to focus on the development of EDI200. They traveled all over the world searching for funding to continue the research. Their search ended successfully in late 2008 when they connected with Philip Reilly, M.D., J.D. and Third Rock Ventures, a venture capitalist firm in Boston. Third Rock Ventures was interested in rare disorders and specifically XLHED and launched Edimer Pharmaceuticals, Inc. – a U.S.-based company – on July 1, 2009.

According to Dr. Kirby, “As the focus of development moves to the United States, we have been particularly concerned about maintaining continuity with the key people who have played important roles with EDI200. As such, Dr. Schneider and Dr. Gaide are working closely with us as advisors and are performing many key experiments in their labs to understand more about the EDAR/EDA1 pathway and how EDI200 works. Christophe Maier and Stephane Demotz will also play important roles as EDI200 moves into the clinical phase.”