Genethon and Sarepta Extend Collaboration to Develop DMD Gene Therapy

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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Note: This story was updated Dec. 17, 2020, to note that preclinical studies testing this form of gene therapy were conducted in animals that naturally develop DMD, not genetically engineered animals.

Genethon and Sarepta Therapeutics have extended their original agreement to develop GNT0004, a potential gene therapy for the treatment of Duchenne muscular dystrophy (DMD) that is expected to initiate clinical testing in the coming months.

In collaboration with investigators from the University of London, Genethon has developed a gene therapy that uses a harmless adeno-associated viral vector (AAV) to deliver a gene producing a short, artificial form of dystrophin — called microdystrophin — into muscle cells. Loss of dystrophin, a key protein protecting muscle fibers, is a hallmark of DMD.

When tested in dogs that naturally develop DMD symptoms, this approach increased the production of microdystrophin in muscle cells, restored muscle function, and stabilized clinical signs of the disease over more than two years.

Based on these findings, Genethon and Sarepta partnered in 2017 to develop GNT0004. The extension of this agreement reinforces their commitment to co-develop this microdystrophin-based gene therapy.

“This cutting-edge technology is the result of years of research and development based on the expertise of Genethon researchers, pioneers in the field of gene therapy for rare diseases. Combining this promising approach, which targets the majority of Duchenne patients, with the know-how of our partner Sarepta is a new opportunity for patients,” Frédéric Revah, CEO of Genethon, said in a press release.

“We have just started a clinical study of pre-inclusion of patients (“baseline” study) to allow us to precisely evaluate the efficacy of the product. This is a very concrete step towards the injection of the first patient with the product in the coming months,” Revah said.

Under the terms of the agreement, Genethon will be responsible for commercializing GNT0004 in Europe (excluding the U.K.), while Sarepta will be marketing the therapy in the rest of the world.

Genethon, a nonprofit organization based in France, will receive an upfront payment from Sarepta and may receive royalties and additional payments for each developmental and commercial milestone achieved.

Both companies are collaborating with Yposkesi, a large European facility, to produce large-scale batches of viral vectors for GNT0004.

To meet these demands, Yposkesi is planning to double the size of its production facilities to increase the capacity of its bioreactors — large containers used for biological reactions and to culture cells or living tissues.

With the construction of an additional production facility already underway, the company is anticipating to deliver the first batches by 2022 or 2023, which will be produced with Yposkesi’s suspension production method.

“Yposkesi is proud to have been selected to produce and deliver AAV material at large-scale using its proprietary suspension-based process for Duchenne muscular dystrophy, a neuromuscular disease that requires high doses,” Alain Lamproye, CEO of Yposkesi, said in another press release.

“The significant investments made in honing our expertise, expanding our facilities, as well as developing innovations to increase production capacity and process efficiency are aimed at serving gene therapy developers, especially those currently facing a bottleneck in manufacturing,” Lamproye said.