Ultragenyx and Solid Biosciences Partner on DMD Gene Therapy

Aisha I Abdullah PhD avatar

by Aisha I Abdullah PhD |

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Ultragenyx Pharmaceutical and Solid Biosciences announced a strategic collaboration to develop and commercialize new gene therapies for Duchenne muscular dystrophy (DMD).

The collaboration will combine Solid’s gene therapy construct for DMD and Ultragenyx’s cell line platform used for large-scale manufacturing of treatment candidates delivered in adeno-associated viral (AAV) vectors. AAVs are engineered viruses used to deliver gene therapies to cells.

“We believe we can leverage our mutual strengths to develop a high-quality AAV-based treatment alternative for Duchenne,” Emil D. Kakkis, MD, PhD, president and CEO of Ultragenyx, said in a press release.

The proposed new therapies will use an AAV variant (AAV8) that has been successfully validated in humans and can be produced in an efficient, large-scale process, said Kakkis.

DMD is caused by mutations in the DMD gene that result in a deficiency of the protein dystrophin that is critical to muscle fiber function and stability. Dystrophin deficiency leads to diminished nitric oxide production, which is vital for healthy muscle metabolism, function, and structure.

Solid developed the DMD gene therapy candidate SGT-001, which delivers a form of dystrophin called microdystrophin to muscle cells. The treatment, which is administered by intravenous (into the vein) infusions, consists of a shorter version of dystrophin that has the key components of the normal protein.

Microdystrophin contains a domain that binds neuronal nitric oxide synthase (nNOS), the enzyme that synthesizes nitric oxide. In preclinical studies, animals given the microdystrophin gene to restore nNOS levels showed improved resistance to fatigue.

The ongoing Phase 1/2 clinical study in 16 boys and adolescents with DMD, called IGNITE DMD (NCT03368742), has shown positive preliminary results three months after treatment, such as elevating microdystrophin to 17.5% of healthy dystrophin levels, and evidence of nNOS activity and function in two boys.

The U.S. Food and Drug Administration (FDA) recently lifted a second clinical hold on IGNITE DMD, which was due to serious adverse side effects related to SGT-001 experienced by a 7-year-old boy. The boy received the higher of two doses of SGT-001, 2e14 vector genomes /kg, and experienced complications such as low platelet and red blood cell levels, and kidney damage. All these complications were fully resolved. Solid provided the latest safety and effectiveness data, modified the trial’s protocol, and changed the therapy’s manufacturing process as a response to the clinical hold.  

SGT-001 was granted rare pediatric disease and fast track designations in the U.S., and orphan drug designations in both the U.S. and the European Union for the treatment of DMD.

Under the terms of the agreement, Ultragenyx has invested $40 million in Solid for therapeutic product development and will make milestone payments of up to $255 million per product. The agreement grants Ultragenyx exclusive license for any therapy using Solid’s microdystrophin construct for the treatment of DMD and other dystrophin deficiency disorders, such as Becker MD.