Analysts at BMO Capital Markets expect the lack of other exon-44-skiping therapies to facilitate a “smooth” approval process for Avidity’s del-zota.
Avidity’s investigational exon-44-skipping therapy reversed disease progression and improved functional outcomes in patients with Duchenne muscular dystrophy (DMD) in two mid-stage trials after one year of treatment.
In a note to investors on Wednesday morning, BMO Capital Markets noted that delpacibart zotadirsen—also known as del-zota—demonstrated “robust” biomarkers, which then translated to “functional improvements.” The readout, the analysts added, “further derisks” a biologics license application for the asset and suggests a “clear” path to approval.
Avidity is aiming to complete a submission by the end of 2025 to seek accelerated approval for del-zota, according to a company announcement. The biotech is also preparing a confirmatory trial for the antibody-oligonucleotide conjugate (AOC), with an eye toward full global approval.
If approved, del-zota could help Avidity transition “into a commercial-stage company in ~2026,” BMO wrote on Wednesday. “We expect lack of approved Exon-44 skipping treatments to facilitate a smooth BLA submission/approval for del-zota.” The group anticipates around 1,000 addressable U.S. patients.
Wednesday’s findings come from the Phase I/II EXPLORE44 and EXPLORE44-OLE studies. The former enrolled 26 patients with DMD who are amenable to exon 44 skipping, while the latter included 16 participants from EXPLORE44 who continued on to the open-label extension study. Both trials were designed to evaluate the safety of del-zota and assess its effects on key disease biomarkers.
The experimental therapy resulted in a roughly 25% increase in the production of normal dystrophin, a protein associated with muscle dysfunction in DMD. Del-zota restored dystrophin concentrations to up to 58% of normal. Additionally, treatment with the AOC led to a rapid and more-than 80% drop in creatine kinase (CK) levels, a marker indicative of muscle damage. CK concentrations were maintained at “near normal levels” through 16 months of follow-up.
The EXPLORE44 data also showed that these biomarker improvements correlated with functional benefits, as assessed against a natural-history control. Patients on del-zota saw a 2.1-second improvement in the four-stair climb test, versus a 2.7-second decline in natural history controls. The AOC likewise resulted in better outcomes in the 10-meter walk/run, time to rise from floor and North Star Ambulatory Assessment tests.
Del-zota’s readout on Wednesday could further improve Avidity’s image to potential buyers. In August, The Financial Times reported that Novartis had approached the biotech with a buyout offer—but no such deal has yet come to fruition. The pharma has since made several big-ticket buys, including the $1.4 billion takeover of Tourmaline Bio on Tuesday and a $5.2 billion commitment last week to expand its ongoing agreement with China’s Argo Biopharma.
