- The stock price of Alnylam Pharmaceuticals (ALNY) surged by 49.33% in the previous trading session. This is why.
The stock price of Alnylam Pharmaceuticals (ALNY) surged by 49.33% in the previous trading session. Investors responded positively to Alnylam Pharmaceuticals announcing that the APOLLO-B Phase 3 study of patisiran, an investigational RNAi therapeutic in development for the treatment of transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy, met the primary endpoint of change from baseline in the 6-Minute Walk Test (6-MWT) at 12 months compared to placebo (p-value 0.0162).
This study also met the first secondary endpoint of change from baseline in quality of life compared to placebo, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) (p-value 0.0397). And the study also included additional secondary composite outcome endpoints to be tested in a hierarchical manner. A non-significant result (p-value 0.0574) was found on the secondary composite endpoint of all-cause mortality, frequency of cardiovascular events, and change from baseline in 6-MWT over 12 months compared to placebo.
As a result, the formal statistical testing was not performed on the final 2 composite endpoints, which were not powered for statistical significance given the short duration of the study — all-cause mortality and frequency of all-cause hospitalizations and urgent heart failure visits in patients not on tafamidis at baseline (nominal p-value 0.9888), and in the overall population (nominal p-value 0.5609). Patisiran also demonstrated an encouraging safety and tolerability profile, with deaths numerically favoring the patisiran arm.
APOLLO-B is a Phase 3, randomized, double-blind, placebo-controlled multicenter global study designed and powered to evaluate the effects of patisiran on functional capacity and quality of life in patients with ATTR amyloidosis with cardiomyopathy. And the study enrolled 360 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy at 69 sites in 21 countries. Patients were randomized 1:1 to receive 0.3 mg/kg of patisiran or placebo intravenously administered every three weeks over a 12-month double-blind treatment period. After 12 months, all patients will receive patisiran in an open-label extension period.
The primary endpoint of APOLLO-B is the change from baseline in the 6-MWT at 12 months compared to placebo. And the secondary endpoints evaluate the efficacy of patisiran vs. placebo over 12 months in a hierarchical manner with the following measures:
1.) Health-related quality of life with the KCCQ change from baseline at 12 months;
2.) Composite of all-cause mortality, frequency of cardiovascular (CV) events (CV hospitalizations and urgent heart failure (HF) visits) and change from baseline in 6-MWT;
3.) Composite of all-cause mortality and frequency of all-cause hospitalizations and urgent HF visits in patients not on tafamidis at baseline; and
4.) Composite of all-cause mortality and frequency of all-cause hospitalizations and urgent HF visits in the overall study population.
Exploratory endpoints included cardiac biomarkers and various imaging tools to further characterize the potential burden of cardiac involvement in these patients. And the overall safety profile of patisiran during the 12-month double-blind period was encouraging.
1.) 5 patients (2.8%) on patisiran and 8 patients (4.5%) on placebo died. And the number of deaths in the all-cause mortality efficacy analysis was 4 (2.2 percent) in the patisiran arm and 10 (5.6 percent) in the placebo arm, determined in accordance with the pre-defined statistical analysis plan, which excluded death due to COVID-19, and treated cardiac transplant as a death event consistent with other studies in the field.
2.) The patisiran and placebo arms had similar frequencies of adverse events (AEs) (91.2% and 94.4%, respectively) and serious adverse events (SAEs) (33.7% and 35.4%, respectively). And AEs reported in greater than or equal to 5 percent of patisiran patients and seen at least 3 percent more frequently with patisiran compared with placebo were infusion-related reactions (12.2 percent vs. 9 percent, respectively), arthralgia (7.7 percent vs. 4.5 percent, respectively), and muscle spasms (6.6 percent vs. 2.2 percent, respectively). No SAEs occurred at least 2 percent more frequently in patisiran versus placebo treated patients.
The full results of the APOLLO-B study will be presented as part of a late-breaker session at the 18th International Symposium on Amyloidosis on September 8, 2022, in Heidelberg, Germany.
“We are thrilled that APOLLO-B successfully met all its major objectives, which we believe for the first time validates the hypothesis that TTR silencing by an RNAi therapeutic can be an effective approach for treating the cardiomyopathy of ATTR amyloidosis. ATTR amyloidosis with cardiomyopathy is an increasingly recognized cause of heart failure, affecting greater than 250,000 patients around the world. These patients have limited treatment options, and disease progression is common. As such, we are encouraged to see the potential of patisiran to improve the functional capacity and quality of life of patients living with this fatal, multi-system disease. I want to thank all the patients, caregivers, investigators, and study staff who have and continue to participate in APOLLO-B. We look forward to sharing full results at an upcoming conference in September, and based on these positive results, we plan to submit a supplemental NDA for patisiran with the U.S. Food and Drug Administration in late 2022.”
— Pushkal Garg, M.D., Chief Medical Officer of Alnylam
“I am delighted by the results of the APOLLO-B study, which suggest the potential for patisiran to be a treatment option for patients with ATTR amyloidosis with cardiomyopathy, assuming favorable regulatory review. In addition, the APOLLO-B data further strengthen our confidence in our Phase 3 HELIOS-B study of vutrisiran in ATTR amyloidosis with cardiomyopathy, which is expected to report out in early 2024. Today’s positive results advance our goal to establish an industry leading TTR franchise, which currently includes ONPATTRO and AMVUTTRATM for the polyneuropathy of hereditary ATTR amyloidosis. We believe these data take us one step closer to achieving our Alnylam P5x25 vision of becoming a leading biopharma company.”
— Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam