Novartis said two Phase III studies of investigational medicines—pelacarsen for cardiovascular disease and delpacibart etedesiran, or del-desiran, for myotonic dystrophy type 1—failed to meet their primary endpoints.
The Lp(a)HORIZON trial evaluated pelacarsen in 8,323 patients with elevated lipoprotein(a), or Lp(a), and established cardiovascular disease. The study did not show a statistically significant reduction versus placebo in a composite of cardiovascular death, non-fatal heart attack, non-fatal stroke and urgent coronary revascularization requiring hospitalization.
Pelacarsen did reduce Lp(a) levels in patients receiving guideline-directed care, including lipid-lowering and antihypertensive therapies. However, Novartis said the lower Lp(a) levels did not translate into reduced cardiovascular risk in the overall trial population.
Pelacarsen is an antisense oligonucleotide designed to inhibit production of Lp(a), an inherited cardiovascular risk factor. Elevated Lp(a) affects about one in five people worldwide, according to Novartis, and there is no approved targeted treatment. The company obtained worldwide rights to pelacarsen through a license and collaboration agreement with Ionis Pharmaceuticals.
Separately, Novartis said the Phase III HARBOR study of del-desiran did not demonstrate statistically significant improvement against placebo on video hand opening time, a measure of hand myotonia in people with myotonic dystrophy type 1.
The 54-week global study enrolled about 150 people with the progressive neuromuscular disease, which has no approved treatment. Participants received del-desiran or placebo every eight weeks.
Novartis reported signs of clinical activity in secondary endpoints and exploratory analyses, while safety findings were generally consistent with previously reported data. The company will analyze the full dataset and discuss a potential development path with health authorities.
Del-desiran is an antibody-oligonucleotide conjugate designed to reduce toxic DMPK messenger RNA in muscle cells. It entered Novartis’ pipeline through the company’s acquisition of Avidity Biosciences.
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