Sarepta Licenses Experimental Gene Therapy Pre-Treatment from Hansa Biopharma

Rare Daily Staff

Sarepta Therapeutics has obtained an exclusive global license to develop and promote Hansa Biopharma’s imlifidase as a pre-treatment for gene therapy in Duchenne and limb-girdle muscular dystrophy patients who have pre-existing antibodies to AAV.

Duchenne muscular dystrophy (DMD) is a rare, degenerative neuromuscular disorder causing severe progressive muscle loss and premature death. Limb-girdle muscular dystrophy (LGMD) describes a group of more than 30 distinct diseases that cause weakness and wasting of the muscles around the hips and shoulders, eventually progressing to the arms and legs. LGMD can be caused by a single gene defect that affects specific proteins within the muscle cell, including those responsible for keeping the muscle membrane intact.

Under the terms of the agreement, Hansa will receive an upfront payment of $10 million and is eligible for additional development, regulatory and sales milestone payments potentially totaling up to $397.5 million. Hansa will book all sales of imlifidase and will earn tiered royalties up to the mid-teens on any incremental gene therapy sales that arise from treating antibody-positive patients enabled through imlifidase pre-treatment.

Sarepta’s experimental gene therapies use an adeno-associated virus (AAV) and patients with DMD and LGMD who have pre-existing IgG antibodies are not currently eligible for treatment with any AAV-based gene therapies. Imlifidase is an antibody-cleaving enzyme that specifically targets IgG and inhibits an IgG-mediated immune response. Imlifidase has a rapid onset of action, cleaving IgG-antibodies and inhibiting their reactivity within hours after administration, thus clearing the AAV-IgG antibodies that would typically preclude dosing or re-dosing with AAV.

“One of the current limitations of gene therapy is the inability to treat patients who have pre-existing neutralizing antibodies to the AAV vector. While our AAVrh74 vector has been associated with a low screen out rate for neutralizing antibodies, even that low rate is inconsistent with our mission,” said Doug Ingram, president and CEO of Sarepta.  “In pre-clinical and clinical models, Hansa’s technology has shown the ability to clear the IgG antibodies that prevent dosing AAV-based gene therapies. If successful, this could offer the potential of extending our gene therapy treatments to DMD and LGMD patients who would otherwise have been denied access due to pre-existing antibodies.”

With five LGMD gene therapy programs in development and an option for a sixth program, Hansa’s pre-treatment technology is not the only method Sarepta is trying out. Only two weeks ago, Sarepta entered into an option to license agreement with Selecta Biosciences for rights to develop and commercialize Selecta’s immune tolerance platform ImmTOR as a way to minimize or prevent the formation of neutralizing antibodies to AAVs. And in November, Sarepta struck a deal with StrideBio to use its technology to develop gene therapies for up to eight central nervous system and neuromuscular targets. StrideBio’s structure-driven capsid technology is intended to enhance specific tropism to tissues of interest and evade neutralizing antibodies.

Photo: Doug Ingram, president and CEO of Sarepta