A $12B Avidity asset hit its phase 1/2 primary endpoint on a DUX4 regulated biomarker. The agency has not been asked yet, and the question is whether KHDC1 counts as evidence in a disease with no approved therapy.
Novartis reported on Friday that delpacibart braxlosiran did what it was designed to do: move a number that the company says matters. The drug, an antibody-oligonucleotide conjugate now in Novartis' hands after the company's $12 billion acquisition of Avidity Biosciences, lowered plasma levels of KHDC1 in a 51-subject phase 1/2 biomarker cohort, and reduced creatine kinase alongside it. The wire called that a win. The harder question is what the FDA does with it.
KHDC1 is a circulating protein regulated by DUX4, the gene whose abnormal reactivation drives facioscapulohumeral muscular dystrophy (FSHD). Treating a DUX4-regulated biomarker as a surrogate for clinical benefit is the bet Novartis is making. FSHD has no approved therapy, no validated surrogate endpoint, and a regulatory track record on accelerated approval that the agency has not yet written. Chief executive Vas Narasimhan said in April that the company would ask the FDA about an accelerated path on the strength of phase 1/2 biomarker data, according to the Fierce Biotech report on the readout. The agency has not been asked. The conversation is what comes next.
The phase 3 trial, which started last year, is still running. Its 78-week clinical endpoint is the actual test of whether the biomarker signal translates into something patients can feel. The accelerated-approval track, if Novartis opens it, runs in parallel, not in place of that outcome trial. A biomarker-driven approval in FSHD would not only change the regulatory playbook for the disease; it would also set precedent for the broader class of antibody-oligonucleotide conjugates, including the rest of the assets that came with the Avidity deal.
Sarepta is also in this field. Its SRP-1001 program, picked up from Arrowhead for $500 million upfront, has produced biomarker data that TD Cowen analysts called "potentially superior" in select readouts, per the same Fierce Biotech coverage. The competition is no longer theoretical. Two sponsors are now asking, in effect, whether the FDA will accept DUX4-regulated biomarkers as adequate evidence in a disease that has waited decades for any therapy at all.
What the FDA says in that conversation decides whether del-brax becomes the first FSHD drug, whether the AOC platform that Novartis paid $12 billion for has a regulatory path beyond the obvious targets, and whether the Sarepta program gets a faster road by being second to a credible surrogate. The biomarker did its job. The decision is not Novartis' to make.