Pharmavitae Analytics predicts that the launch trajectory of patisiran for hATTR amyloidosis with polyneuropathy will depend on the education of physicians in multiple specialties on this rare condition (Alnylam, 2017b), and this new drug class. Pharmavitae Analytics anticipates that market penetration of patisiran will be high among correctly diagnosed patients, due to the lack of effective available treatments, but physicians’ poor awareness of the difficult to diagnose orphan disease will be a significant barrier. The different symptoms of hATTR amyloidosis with polyneuropathy can cause patients to see multiple specialists, including primary care physicians, gastroenterologists, urologists, and neurologists, and this process commonly takes four to five years to reach a diagnosis (Alnylam, 2017b).
Pharmavitae Analytics polled neurologists based in the US, France, Germany, Italy, Spain, and the UK on the APOLLO results, and found that out of 50 neurologists who are both familiar with the topline Phase III data and currently treat hATTR amyloidosis patients with polyneuropathy, 24 out of 25 (96%) neurologists based in the US and 23 out of 25 (92%) neurologists based in Europe would prescribe patisiran for hATTR amyloidosis patients with polyneuropathy if the RNAi drug is approved. Pharmavitae Analytics notes that this high acceptance rate is potentially biased by the fact that only neurologists who are both aware of the APOLLO data and currently treating hATTR amyloidosis patients with polyneuropathy responded to the survey question.
Pharmavitae Analytics predicts that the APOLLO trial results will improve sentiment toward the RNAi therapeutics class after recent safety issues with Alnylam’s RNAi therapeutics clinical portfolio. Pharmavitae analytics expects that the APOLLO safety data will help to mitigate any remaining concerns from Alnylam’s discontinuation of its Phase III RNAi drug candidate revusiran for the treatment of hATTR amyloidosis with cardiomyopathy in October 2016 (Alnylam, 2016), and suspension of its Phase III RNAi therapeutic candidate fitusiran for the treatment of hemophilia A and B patients with and without inhibitors in September 2017 (Alnylam, 2017c).
Alnylam discontinued the ENDEAVOUR Phase III study of revusiran in hATTR amyloidosis with cardiomyopathy due to incidences of new onset or worsening peripheral neuropathy in the Phase II open-label extension study of revusiran, and subsequently uncovered an imbalance of mortality in the revusiran arm compared with placebo in the ENDEAVOUR study (Alnylam, 2016). Alnylam also suspended dosing in all ongoing fitusiran studies due to a fatal thrombotic event in a patient with hemophilia A without inhibitors in the Phase II open-label extension study of fitusiran (Alnylam, 2017c). Alnylam said that it aims to resume dosing of fitusiran as soon as possible, and potentially as early as late 2017, following further investigation of the safety finding, and upon agreement with regulatory authorities, with appropriate protocol amendments for enhanced safety monitoring (Alnylam, 2017c). The negative benefit-risk profile signals from these two drugs in Alnylam’s investigational RNAi therapeutics portfolio did however threaten market confidence in the novel drug class.
Alnylam (2016) Alnylam Pharmaceuticals Discontinues Revusiran Development. Available from: http://investors.alnylam.com/releasedetail.cfm?ReleaseID=992320[Accessed 20 September 2017].
Alnylam (2017a) Alnylam and Sanofi Report Positive Topline Results from APOLLO Phase 3 Study of Patisiran in Hereditary ATTR (hATTR) Amyloidosis Patients with Polyneuropathy. Available from: http://investors.alnylam.com/releasedetail.cfm?ReleaseID=1041081 [Accessed 20 September 2017].
Alnylam (2017b) Alnylam Pharmaceuticals Conference Call to Discuss Topline Results from APOLLO Phase 3 Study of Patisiran. Available from: http://investors.alnylam.com/eventdetail.cfm?EventID=185171 [Accessed 20 September 2017].
Alnylam (2017c) Alnylam Provides Pipeline Update on Fitusiran and Givosiran Investigational RNAi Therapeutic Programs. Available from: http://investors.alnylam.com/releasedetail.cfm?ReleaseID=1039464 [Accessed 20 September 2017].
Ionis (2017) Ionis to Independently Advance Inotersen and IONIS-FB-L Rx. Available from: http://ir.ionispharma.com/news-releases/news-release-details/ionis-independently-advance-inotersen-and-ionis-fb-l-rx [Accessed 20 September 2017].
Sanofi (2017) Sanofi and Alnylam Report Positive Topline Results from APOLLO Phase 3 Study of Patisiran in Hereditary ATTR (hATTR) Amyloidosis Patients with Polyneuropathy. Available from: http://news.genzyme.com/press-release/sanofi-and-alnylam-report-positive-topline-results-apollo-phase-3-study-patisiran-here [Accessed 20 September 2017].