Hansa Biopharma announced topline results from three Duchenne muscular dystrophy (DMD) patients who received imlifidase pre-treatment before Sarepta's ELEVIDYS gene therapy in the SRP-9001-104 trial, marking the first clinical demonstration of overcoming antibody barriers to gene therapy access.
Breakthrough in Antibody Reduction
After one dose of imlifidase, all three patients experienced rapid reduction of IgG antibodies to levels ≥95% less than baseline. Critically, pre-existing anti-AAV antibodies were reduced below a titre of 1:400, which enabled treatment with ELEVIDYS. The safety profile of imlifidase remained consistent with prior experience, and the trial generated no new safety signals.
"These are the first results from a clinical trial, assessing imlifidase's potential for patients with high levels of anti-AAV antibodies to access approved gene therapies," said Renée Aguiar-Lucander, CEO of Hansa Biopharma. "We are encouraged that imlifidase was able to substantially reduce both IgG antibodies and pre-existing anti-AAV-antibodies, to enable patients to be treated with gene therapy."
Gene Therapy Outcomes and Next Steps
Twelve weeks after ELEVIDYS administration, patients demonstrated evidence of AAV-mediated transduction and expression of micro-dystrophin, though levels were lower than seen in other ELEVIDYS trials. Based on these outcomes, Hansa and Sarepta will discuss appropriate next steps for the program.
Addressing Unmet Medical Need
The SRP-9001-104 trial enrolled ambulatory male patients with DMD between four and nine years of age who had pre-existing antibodies to ELEVIDYS. All patients included were previously ineligible to receive ELEVIDYS due to antibodies targeting AAVrh74, the vector used to deliver Sarepta's gene therapy treatment.
DMD is a rare and fatal genetic disease caused by a mutation in the DMD gene encoding for dystrophin. The irreversible, progressive disease causes muscle weakness and damage over time, leaving most patients wheelchair-bound by age 12. DMD affects one in 3,500 to 5,000 males born worldwide, with approximately 14% of DMD patients having pre-existing IgG antibodies to the rh74 vector.
Broader Implications for Gene Therapy Access
Currently, neutralizing antibodies prevent an estimated one in three people from benefiting from gene therapy treatments. Many gene therapies rely on Adeno Associated Virus (AAV) vectors, but some patients carry antibodies that counteract treatment effectiveness.
Pre-treatment with imlifidase prior to AAV-based gene therapy has the potential to inactivate antibodies and enable gene therapy in patients with pre-existing antibodies to AAV-based treatments. Hansa expects to report data from another ongoing gene therapy collaboration later this year to continue collecting evidence of imlifidase's potential benefits in gene therapy applications.
