Alnylam reports 18-month APOLLO-B data for Onpattro in ATTR-cardiomyopathy, updates sNDA

Alnylam Pharmaceuticals is so pleased with 18-month data from its Phase III trial investigating Onpattro as a treatment of ATTR cardiomyopathy that it submitted it as an amendment to its sNDA as analysts expect approval later this year with the data strengthening the application.

The trial, dubbed APOLLO-B, investigated the drug’s impact on the quality of life in patients with ATTR amyloidosis against a placebo. At the 12-month double-blinded (DB) assessment, the trial already hit its primary endpoint, which looked at the six-minute walk test in patients taking the drug against a placebo.

Using the six-minute walk test against the placebo, patients taking the drug saw a -9.2 meters difference at the 18-month mark. For patients initially randomized to placebo but switched to Onpattro, the company noted that the drug still slowed the rate of worsening: The mean change from baseline to month 12 was 25.4 meters, and to month 18 was 31.1 meters in the walk test.

At the 18-month mark, there was also “relative stability” in biomarker measures of cardiac stress and cardiac injury. Patients who received the placebo in the 12-month double-blind period showed steadily rising cardiac biomarker levels, which appeared to slow or stabilize after they started taking Onpattro.

Alnylam added that while the trial was not designed to show a treatment difference in the composite endpoints of death and hospitalizations “and no statistically significant differences were achieved,” there was “evidence of favorable trends” for both.

Back in February, the FDA accepted a sNDA for Onpattro, otherwise known as patisiran, to treat the cardiomyopathy of transthyretin-mediated (ATTR) amyloidosis. The FDA will be holding a meeting of the Cardiovascular and Renal Drugs Advisory Committee to discuss the application. The expected PDUFA date is Oct. 8.

Onpattro is already approved for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults.

Rena Denoncourt

“The results demonstrate that serum TTR reduction with an RNAi therapeutic has the potential to provide sustained clinical benefit through 18 months of treatment,” Rena Denoncourt, VP and TTR franchise lead at Alnylam, said in a statement. “These data, in conjunction with the observed decline in placebo-treated patients during the DB period, reinforce the importance of early treatment initiation in ATTR amyloidosis.”

Analysts from William Blair agreed that early treatment with Onpattro in patients is key, noting that the improvement in the patients who switched from placebo was less than what was seen in the first six months of treatment in the double-blind period. Analysts said that “illustrates  that the disease-modifying treatment is unlikely to be regenerative and earlier intervention is likely to lead to improved outcomes, as is often the case with progressive pathologies.”

William Blair analysts added that the potential mortality benefit is “intriguing” and will likely be discussed at the upcoming adcomm, where they expect approval of the drug.

Maury Raycroft from Jefferies said the data further strengthens the sNDA package and that they expect the upcoming adcomm to focus on safety, benefit across subgroups, strength of placebo-controlled data and having a second trial.

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