Patisiran Proven to Reduce Hospitalization and Mortality in hATTR Patients


At the 70th Annual AAN 2018 Annual Meeting, Alnylam announced new results from the APOLLO Phase 3 study of patisiran, an investigational RNAi therapeutic for the treatment of hATTR amyloidosis.

This morning at the 70th Annual American Academy of Neurology (AAN) 2018 Annual Meeting, Alnylam Pharmaceuticals, Inc. announced new results from the APOLLO Phase 3 study of patisiran, an investigational RNAi therapeutic for the treatment of hereditary ATTR (hATTR) amyloidosis.

The results were presented at the meeting’s Clinical Trials Plenary Session in a presentation titled, “Patisiran, an Investigational RNAi Therapeutic for Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis: Results from the Phase 3 APOLLO Study,” by David Adams, MD, PhD, from the Department of Neurology at Bicêtre Hospital, Greater Paris University Hospitals. Dr Adams served as the Principal Investigator for the trial.

The APOLLO Phase 3 trial was a randomized, double-blind, placebo-controlled, global study intended to assess the safety and efficacy of patisiran in hATTR amyloidosis patients with associated polyneuropathy. It is the largest clinical study of patients with hATTR amyloidosis conducted to date, with 225 hATTR amyloidosis patients enrolled from 19 countries with 29 genotypes. They were randomized 2:1, patrisiran: placebo, with patisiran administered at 0.3 mg/kg once every 3 weeks for 18 months.

Change from baseline in modified Neurologic Impairment Score +7 (mNIS+7) relative to placebo at 18 months served as the primary endpoint, and secondary endpoints included: the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) score; NIS-weakness (NIS-W); Rasch-built Overall Disability Scale (R-ODS); timed 10-meter walk (10-MWT); modified BMI (mBMI); and the composite autonomic symptom score-31 (COMPASS-31).

The newly revealed post-hoc analysis exhibited an estimated 50% decrease in the composite rate of all-cause hospitalization and mortality over 18 months in patients treated with the drug, compared to patients who received placebo.

“We believe these results, along with previously presented APOLLO data that show halting or reversal of neuropathy progression in a majority of patients treated with patisiran, strengthen the body of evidence demonstrating that patisiran, if approved, has the potential to be a transformative treatment for patients with all forms of hereditary ATTR amyloidosis,” said Eric Green, Vice President and General Manager, TTR Program at Alnylam in a press release. “We continue to work collaboratively with the FDA and EMA through patisiran’s review process, with the goal of making this medicine available to patients as quickly as possible, upon approval.”

Patisiran exhibited halting or improvement in the modified NIS+7 (mNIS+7) primary endpoint in patients irrespective of severity of baseline neuropathy, compared to the progression in mNIS+7 reported in patients treated with placebo. While treatment benefit is observed across all stages of disease, these results support the rationale for early treatment with patisiran to potentially halt or improve neuropathy progression or impairment, respectively.

Overall, it was reported that, in patients treated with patisiran, benefits were seen in motor, sensory and autonomic neuropathy, and positive effects were observed across a wide range of severity, benefiting patients in both early and advanced stages of the disease, as well as TTR geneotypes, and in patients with associated cardiac involvement. A significant improvement was seen in quality of life (QoL), reduction in disease symptoms and disability, and improvement was also seen in nutritional status, strength, and ambulation with patisiran relative to placebo.

Patisiran showed an encouraging safety and tolerability profile, with frequency of patient deaths trending lower in the patisiran group than in the placebo group.

99% of all eligible patients from the APOLLO study have been enrolled into a global open-label extension (OLE) study.

In the video below, Mathew Maurer, MD, Arnold and Arlene Professor of Cardiology at Columbia University, explains the genetics of hATTR Amyloidosis.

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  1. Adams D, Gonzalez-Duarte A, O’Riordan W, et al. Patisiran, an Investigational RNAi Therapeutic for Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis: Results from the Phase 3 APOLLO Study. Presented at: 70th Annual American Academy of Neurology (AAN) 2018 Annual Meeting; April 21-27, 2018; Los Angeles, California.
  2. Alnylam Reports New Clinical Results from the APOLLO Phase 3 Study of Patisiran at the American Academy of Neurology 2018 Annual Meeting. Accessed April 24, 2018.
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