In the wake of its high-profile setback in heart disease late last week, Swiss pharma giant Novartis really needed a win, but has flopped again, reports Endpoints News.
On Tuesday, it reported that in a late-stage trial, an antibody-oligonucleotide conjugate that it got from Avidity Biosciences was not statistically significantly better than placebo in patients with a neuromuscular disease called myotonic dystrophy type 1 (DM1).
The HARBOR study was investigating delpacibart etedesiran, or del-desiran for short. It has a primary endpoint of video hand opening time, which is a way of measuring how well patients’ hand muscles relax after contracting.
The study miss, plus that of the Lp(a)HORIZON trial of the heart drug pelacarsen, which was disclosed as a failure on Friday, wiped 10% off Novartis’ Swiss-listed stock in early trading this week.
Novartis got del-desiran when it bought Avidity for about $12bn nearly a year ago. DM1 represented about a third of peak sales from the Avidity acquisition.
Also late last month, three patients in a trial of Novartis’ CAR T programme rapcabtagene autoleucel died due to the immune system becoming dangerously overactive. The pharma paused several of its immunology and neuroscience studies as a result.
What’s left in Avidity deal
DM1 is caused by extra copies of a repeating sequence of three nucleotides in the noncoding region of the DMPK gene. Del-desiran incorporates a small interfering RNA, which is designed to degrade DMPK mRNA, and thus reduce these repeated sequences. The siRNA is bonded to an antibody that binds to the transferrin receptor 1 on muscle cells.
Novartis said there was “evidence of clinical activity in secondary endpoints and exploratory analyses” in HARBOR. Safety was as expected, it added. The company said it would “engage with health authorities to determine the most appropriate development path” for the drug.
Del-desiran is one of three neuromuscular disease-focused conjugates Novartis acquired in the Avidity buyout. One of them is delpacibart zotadirsen (del-zota), which was filed for accelerated approval in June for patients with Duchenne muscular dystrophy and mutations amenable to exon 44 skipping.
A Phase 1/2 trial of the third Avidity asset, delpacibart braxlosiran (del-brax) for facioscapulohumeral muscular dystrophy, yielded positive biomarker data, and Novartis is planning to discuss the next steps with the FDA.
Novartis said that despite the back-to-back trial failures, it was still on course to meet its long-term 2025 to 2030 guidance of between 5% and 6% sales growth per year.
Another company was hit even harder by HARBOR’s failure. Dyne Therapeutics is developing zeleciment basivarsen (z-basivarsen, also known as DYNE-101) for DM1. It is an antisense oligonucleotide designed to bind to DMPK mRNA and it is conjugated with an antigen-binding fragment aimed at transferrin receptor 1.
The drug’s pivotal DM1 study, ACHIEVE, is scheduled to read out early next year, but investors have taken HARBOR’s failure as a bad omen. Dyne’s shares plummeted 30% this week.
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