Novartis has reported a phase 1/2 win for one of the jewels of its $12 billion Avidity Biosciences buyout, setting the Swiss drugmaker up to talk to global regulatory agencies about the next steps for its dystrophy prospect.
Back in April, Novartis CEO Vas Narasimhan, M.D., told investors that the company planned to talk to the FDA about seeking accelerated approval based on the phase 1/2 data. The pharma has already started a phase 3 trial of the candidate, the antibody-oligonucleotide conjugate (AOC) delpacibart braxlosiran (del-brax), but has spied a chance to come to market before that trial wraps up.
Novartis’ topline phase 1/2 data take del-brax a step toward commercialization in facioscapulohumeral muscular dystrophy (FSHD). The 51-subject biomarker cohort hit its primary endpoint, which looked at change in the plasma concentration of KHDC1.
KHDC1 is a circulating biomarker regulated by DUX4. In FSHD, abnormal expression of DUX4 leads to changes in gene expression associated with the lifelong, progressive loss of muscle function. Del-brax combines an siRNA targeting DUX4 mRNA with an anti-TfR1 antibody. The antibody delivers the payload to muscle cells to reduce DUX4 mRNA in target tissues, addressing the underlying cause of FSHD.
Novartis’ phase 3 study, which started last year, is evaluating whether the mechanism improves muscle strength and other clinical outcomes through Week 78. That study will be the acid test of del-brax. But the phase 1/2 data suggest the AOC has the intended biological effects. Novartis reported the drop in KHDC1 alongside a fall in creatine kinase, suggesting target engagement and reduced muscle damage.
It remains to be seen whether the FDA is open to granting accelerated approval based on the phase 1/2 data. Either way, Narasimhan expects del-brax to be the first drug to market in FSHD, reflecting Novartis’ position at the front of a pack of companies that includes Sarepta Therapeutics.
Sarepta posted initial clinical results on its FSHD candidate, SRP-1001, in March. The data on the siRNA drug, which Sarepta picked up from Arrowhead Pharmaceuticals in a deal worth $500 million upfront, impressed TD Cowen analysts. Writing in a note to investors in March, the analysts said the data support SRP-1001’s “potentially superior biomarker efficacy” compared to del-brax.