The future of Sarepta in gene therapy remains obscured, but the data of the partner Hansa is a positive point

Sarepta Therapeutics always assesses the best way to prevent liver damage to its commercial gene therapy of Duchenne muscular dystrophy. But Sarepta’s partner, Hansa Biopharma, encouraged the preliminary data of a small clinical study suggesting that its organ transplant rejection medication could find additional use as an option of pre -treatment for duchenne patients dosed with gene therapy, Elecidys.

In three duchenne patients who received a dose of the Hansa medication, Imlifidase, the company based in Lund, Sweden, reported a rapid reduction in immunoglobulin G (IGG) antibodies, which are antibodies that can cause excessive immune responses. Hansa said he would discuss the next stages of this program with Sarepta, currently in phase 1 tests.

Elecidys is transported to muscle cells aboard an adeno-associated virus (AAV). These engineering viruses can cause excessive immune responses, a known risk of genetic drugs that use AAV for delivery as a delivery vehicle. Immunosuppressive drugs are commonly administered as part of the regime for gene therapies issued by AAV.

Imlifidase works by degrading IGG antibodies. This drug, an engineering enzyme, is already marketed in Europe under the name of brand Idefirix, marketed to prevent the rejection of a transplanted rein. In this indication, the drug does not replace the immunosuppressive treatment that patients should take after a transplant. On the contrary, the medication infused intravenously is used as a pre -treatment for patients who have antibodies against the donor’s kidney.

The preliminary data reported on Friday evening comes from a phase 1 study with a targeted registration of six Duchenne patients who have pre -existing antibodies against AAV. Hansa said the results of three patients have so far shown 95% or more IGG reductions compared to the basic levels. The discounts allowed these patients to receive elevations. Hansa said that 12 weeks after the assay of gene therapy, patients showed evidence that genetic genetic genetic material was delivered to cells, which in turn led to the production of micro-dystrophin, a smaller version of the dystrophin protein that is missing from duchenne patients.

Although the production of micro-dystrophin is encouraging, Hansa noted that the levels of this protein were lower than that was reported in other Elevedys clinical trials. As for security, Hansa said that the drug profile was in accordance with the previous experience and that no new safety signal had been observed. An undesirable event of particular interest in clinical trials of transplantation of immlifidase organs was of low levels of IgG which can lead patients to become more sensitive to infections. European regulators have noted a higher frequency of serious or serious infections have been reported in patients who received the study.

So far, it was a swirling year for Sarepta and for the elements, which is the only gene therapy approved by the FDA for Duchenne. The first death associated with this gene therapy was reported in March. After the second death in June, Sarepta said that he would summon a Duchenne committee and liver experts to discuss the means to mitigate immune responses that lead to liver damage. Sarepta said she would propose to test an already approved immunosuppressant, Sirolimus, based on preclinical data. A third death emerged last month, this time in a participant in the adult clinical trial who received Subeses for a type of Muscular Dystrophy from Girdle of the members.

The FDA initially asked Sarepta to stop sending elements for all Duchenne patients. Sarepta first refused, but then accepted a voluntary break. Last week, the agency told the company that it could resume the shipment of therapy for ambulatory patients, young boys whose duchenne is not as advanced and will not require a higher dose which includes a higher risk of negative effects.

In a note sent to investors on Monday, William Blair analyst Matt Phipps said that the company was pleased to see concept proof for Imlifidase in Duchenne, but the lack of quantitative data is not one of the next stages of the program. The European approval of Imlifidase was a conditional marketing authorization based on a set of thinner evidence. PHIPPS has said that investors are mainly focused on the results of phase 3 of Imlifidase in renal transplants and rare anti-GBM diseases of autoimmune kidney disorders, also called Goodpasture syndrome. The results of the two studies are expected later this year. William Blair expects the results to show a statistically significant advantage in the renal function compared to the care standard measured at one year after the administration of the Imlifidase.

Hansa’s partnership with Sarepta began in 2020, just before the regulatory approval of Imlifidase in Europe to prevent the rejection of transplanted kidneys. Under the terms of the agreement, Sarepta will develop the enzymatic medication as a pre -treatment of Elevedys in the muscular dystrophies of the Duchenne belt and members. Beyond the 10 million dollars that Sarepta paid in Hansa in advance, the Swedish company could receive up to $ 397.5 more linked to the realization of the milestones.

“We are encouraged that Imlifidase has been able to considerably reduce IGG antibodies and pre-existing anti-AV antibodies to allow patients to be treated with gene therapy,” said Hansa Biopharma CEO, Renée Aguiar-Lucande in a prepared statement. “We are also impatient to report data from another collaboration in the process of gene therapy later this year, to continue to collect evidence of the potential advantages of Imlifidase in gene therapy.”

Imlifidase is also currently in phase 2 tests as a pre-treatment for gene therapy that another partner, Genethon, develops for crigler-najjar syndrome, a rare inherited disorder in which the liver cannot decompose bilirubin, a substance formed by red blood cells.

Image of the public domain by the user Flickr Berkshire Community College Bioscience Image Library