18-Month Data for Patisiran in ATTR with Amyloidosis Consistent with Primary Results

Marianna Fontana, MD, PhD
Credit: Asian Society of Cardiovascular Imaging

New data from the phase 3 APOLLO-B study is providing clinicians with additional insight into the effects of patisiran (Onpattro) in the treatment of cardiomyopathy of transthyretin-mediated (ATTR) amyloidosis.

Presented at the Annual Congress of the Heart Failure Association of the European Society of Cardiology (Heart Failure 2023), the latest release of data from the trial’s open-label extension period suggests the benefits of use can be sustained for up to 18 months, with use also associated with significantly improved walking ability relative to placebo therapy.¹

“We are pleased to share encouraging new data from our APOLLO-B OLE study, which we believe continue to support the potential for patisiran to be an important therapeutic option for patients with ATTR amyloidosis with cardiomyopathy,” said Rena N. Denoncourt, vice president, TTR Franchise Lead.²

Already approved by the US Food and Drug Administration for the treatment of polyneuropathy of hereditary ATTR amyloidosis, Alnylam Pharmaceuticals announced the filing a supplemental New Drug Application for patisiran as a treatment for ATTR amyloidosis with cardiomyopathy in December 2022. The basis for the application, the phase 3 APOLLO-B study, which was presented at the 18th International Symposium on Amyloidosis, met its primary endpoint.³

Designed as a double-blind, placebo-controlled trial, the APOLLO-B study randomized patients in a 1:1 ratio to 0.3 mg/kg of patisiran or placebo therapy every 3 weeks over a 12-month period. The primary endpoint of interest for the trial was change in from 6-minute walking test score from baseline to 12 months. Results of the study indicted there was a median difference of 14.7 meters (P = .0162) for 6-minute walking test at 12 months favoring the patisiran group. The trial also met its first secondary endpoint, with use associated with a statistically significant and clinically meaningful benefit on health status and quality of life (P = .0397).⁴

The study from Heart Failure 2023, which was led by Marianna Fontana, MD, PhD, a professor of Cardiology and Honorary Consultant Cardiologist at the National Amyloidosis Centre of the University College London, was an analysis of data from the open-label extension period, which continued for 6 months beyond the trial’s 12-month blinded treatment phase. Results of the analysis suggested the benefits of patisiran were sustained for up to 18 months, with a safety profile consistent with that observed at 12 months.¹

Investigators highlighted use of patisiran was associated with a mean change of —9.2 meters among those randomized to patisiran at baseline, which was consistent with the results observed at the 12-month assessment. Among those randomized to placebo at baseline, the mean change from baseline to month 12 was —25.4 meters and —31.1 meters to month 18. Although not designed to show a treatment difference in clinical outcomes, results suggested there was a favorable, but not statistically significant, trends were observed for all-cause mortality (Hazard ratio [HR], 0.554 [95% CI, 0.281 to 1.094]) and a composite endpoint of all-cause mortality and frequency of all-cause hospitalization and urgent heart failure visits (HR, 0.801 [95% CI, 0.573 to 1.118]).¹

When assessing safety, the release from Alnylam Pharmaceuticals noted no new safety concerns were identified during the open-label extension period , with the majority of adverse events classified as mild or moderate in severity. The release also noted the most common treatment-related adverse event was infusion-related reactions, which occurred among 14.1% of patients receiving patisiran.¹

“The results demonstrate that serum TTR reduction with an RNAi therapeutic has the potential to provide sustained clinical benefit through 18 months of treatment,” Denoncourt added.² “These data, in conjunction with the observed decline in placebo-treated patients during the [double-blind] period, reinforce the importance of early treatment initiation in ATTR amyloidosis. We remain steadfast in our commitment to bring patisiran to patients with ATTR amyloidosis with cardiomyopathy who currently have limited treatment options.”

References

1. Fontana M, Berk JL, Hanna M, et al. Patisiran Treatment for ATTR Cardiac Amyloidosis: 18-Month Results of the Phase 3 APOLLO-B Study. Paper presented at: Annual Congress of the Heart Failure Association of the European Society of Cardiology. Prague, Czech Republic. May 20-23, 2023.
2. Alnylam presents 18-month results from the Apollo-B phase 3 study of patisiran in patients with Attr Amyloidosis. Investor Relations | Alnylam Pharmaceuticals, Inc. May 20, 2023. Accessed May 25, 2023. https://investors.alnylam.com/press-release?id=27561.
3. Alnylam submits Supplemental New Drug Application (sNDA) to U.S. Food and Drug Administration (FDA) for Onpattro. Investor Relations | Alnylam Pharmaceuticals, Inc. December 8, 2022. Accessed May 25, 2023. https://investors.alnylam.com/press-release?id=27121.
4. Alnylam presents positive results from the Apollo-B phase 3 study of patisiran in patients with Attr Amyloidosis. Investor Relations | Alnylam Pharmaceuticals, Inc. September 8, 2022. Accessed May 25, 2023. https://investors.alnylam.com/press-release?id=26936.