UPDATE: Alnylam, Collaborators to Offer New Clinical Data for Patisiran

– Company Presents Positive Initial Data from Phase 2 Open-Label Extension (OLE) Study, Showing Sustained Clinical Activity with TTR Knockdown at the 80% Target Level and Tolerability with Extended Dosing – – Company Also Presents Results of Natural History Study of ATTR Patients with Familial Amyloidotic Polyneuropathy (FAP), Showing Rapid Progression of Neuropathy Impairment Score and Correlation with Disease Severity – Alnylam Pharmaceuticals, Inc. ALNY, a leading RNAi therapeutics company, and collaborators announced today new clinical data for patisiran (ALN-TTR02), an RNAi therapeutic targeting transthyretin (TTR) in development for the treatment of TTR-mediated amyloidosis (ATTR). These data are being presented at the International Symposium on Amyloidosis (ISA) held April 27 – May 1, 2014 in Indianapolis, Indiana. First, the company presented updated Phase 2 results in patients with Familial Amyloidotic Polyneuropathy (FAP) confirming robust TTR knockdown of up to 96% with a mean TTR knockdown of approximately 80%. Further, Alnylam presented preliminary results from the open-label extension (OLE) study with patisiran in patients that were enrolled in the Phase 2 study. Preliminary results from the OLE study showed that multiple doses of patisiran achieved sustained knockdown of serum TTR protein levels at the 80% target level through 168 days. Moreover, OLE results showed a favorable tolerability profile with up to eight doses administered. Finally, the company presented results of a natural history, cross-sectional analysis study of 283 FAP patients aimed at measuring the rate of neuropathy progression and its correlation with disease severity. These results provide support for Alnylam's Phase 3 APOLLO trial where patisiran is being evaluated for its potential efficacy and safety in the FAP indication. “We continue to make strong progress in our patisiran development program, which is focused on making a difference in the lives of ATTR patients with polyneuropathy. Several highlights from our efforts are being presented at ISA, including updated Phase 2 study results, initial data from our Phase 2 OLE study, and results from a natural history study of neuropathy progression in FAP. Notably, our initial results from the Phase 2 OLE confirm a sustained TTR knockdown at the 80% target level through up to 168 days. Further, we are very encouraged by the tolerability data, especially the significant reduction in infusion reactions due to the use of our proprietary micro-dosing regimen. With this early update on the OLE study, we still expect to present clinical endpoint data results later this year consistent with our external guidance,” said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President and Chief Medical Officer of Alnylam. “Another notable highlight is the presentation of FAP natural history study results. This cross-sectional analysis evaluated the neuropathy progression rate in a multinational population of patients with FAP, and demonstrates a rapid progression in NIS and a high correlation of this measurement with disease severity. Moreover, these results give us confidence that our APOLLO Phase 3 trial of patisiran in FAP patients is robustly powered to show the potential impact of TTR lowering on the mNIS+7 endpoint used in that study.” Alnylam presented updated results from its Phase 2 study of patisiran, which was conducted in 29 patients with FAP where patients received two doses of drug administered as an intravenous infusion. As previously reported at the International Society of Familial Amyloidotic Polyneuropathy (ISFAP) meeting in November 2013, patisiran demonstrated a rapid, dose-dependent, and durable knockdown of serum TTR of up to 96% and an average TTR knockdown of approximately 80%. The updated data included results from an additional patient dosed in the study and follow up TTR knockdown data from other patients. The company also presented initial results from its Phase 2 OLE study with patisiran. The OLE study is enrolling patients that were treated in the Phase 2 study and is designed to evaluate the long-term safety and tolerability of patisiran administration. The OLE study is also measuring a number of clinical endpoints every six months, including the modified composite Neuropathy Impairment Score, termed "mNIS+7"; this score is also the primary endpoint of the Phase 3 APOLLO trial of patisiran in FAP. Further, serum TTR levels are being measured following the first dose and then pre-dose every six to twelve weeks; since TTR levels are measured pre-dose, the results are a conservative estimate of TTR knockdown achieved over time with repeat dosing. Of the 29 patients eligible for enrollment, 25 have been enrolled to date and an additional two patients are expected to be enrolled by the end of May; the results from 23 patients are currently evaluable for analysis based on a data cut-off as of April 3, 2014. Preliminary results showed that the TTR knockdown observed following the first dose in the OLE study closely matched TTR knockdown shown in the Phase 2 study, with essentially superimposable pharmacodynamic effects. Moreover, repeat dosing of patisiran led to a sustained TTR knockdown of approximately 80% through up to day 168, equivalent to up to eight doses of drug, as measured in pre-dose blood samples. These data provide the first clinical evidence of sustained, RNAi-mediated TTR knockdown in FAP patients beyond two doses of patisiran. Repeat dosing of patisiran was found to be well tolerated, with minimal adverse events. Importantly, the incidence of infusion-related reactions (IRR) was found to be significantly reduced to 2% in patients from the Phase 2 and Phase 2 OLE studies receiving study drug with a proprietary micro-dosing regimen, as compared with an incidence of 15% in patients receiving a standard infusion (p=0.03). All other reported adverse events were mild to moderate, and there were no changes in liver function tests, renal function, or hematological parameters. Consistent with earlier guidance, Alnylam continues to plan on reporting initial clinical endpoint data from the OLE study in late 2014. Specifically, the company expects to have 6-month mNIS+7 data from approximately 20 patients at that time. The company intends to provide recurrent updates from the OLE study at least annually thereafter. “These preliminary clinical activity and safety data from the OLE study with patisiran are promising. In particular, the potent, rapid, and durable knockdown of TTR achieved by patisiran, which is now confirmed to be sustained with multi-dosing, is important since TTR protein reduction in patients with ATTR may have the potential to delay or even reverse disease progression with associated clinical benefit. It is also encouraging to see the favorable tolerability profile for multiple dose administration of patisiran, including the clear reduction in the occurrence of infusion reactions with micro-dosing,” said David Adams, Head of Department of Neurology and Coordinator of the French Reference Center for FAP (NNERF)/APHP/CHU Bicêtre/France. “I very much look forward to participating in the continued clinical advancement of this RNAi therapeutic, including the ongoing Phase 2 OLE and APOLLO Phase 3 studies, as there are currently few options for our FAP patients suffering from this debilitating, progressive, and life-threatening disease.” Finally, Alnylam and collaborators announced today the results of a 283-patient natural history study of patients with FAP. The aim of the study was to characterize neuropathy severity and rate of progression in a multinational population of FAP patients. The retrospective cross-sectional analysis showed a change in the NIS rate of 14.3 points per year, consistent with the rate of 11.6 points per year observed in the placebo arm of the diflunisal Phase 3 trial, which included both V30M and non-V30M FAP patients. This change in NIS rate corresponds to a change in the mNIS+7 rate of approximately 17.8 points per year. Results demonstrated that NIS is highly correlated with Polyneuropathy Disability (PND) Score (p<0.0001 by ANOVA) and FAP Stage (p<0.0001 by ANOVA). NIS was also shown to be associated with TTR genotype, with the early-onset V30M population exhibiting a significantly lower median NIS compared to late-onset V30M or non-V30M patients (p<0.001). The results of the natural history study provide a solid foundation for the conduct of the ongoing Phase 3 APOLLO trial of patisiran, which is aimed at establishing the efficacy and safety of patisiran in ATTR patients with FAP. About Transthyretin-Mediated Amyloidosis Transthyretin (TTR)-mediated amyloidosis (ATTR) is an inherited, progressively debilitating, and fatal disease caused by mutations in the TTR gene. TTR protein is produced primarily in the liver and is normally a carrier for retinol binding protein. Mutations in TTR cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and/or cardiomyopathy. ATTR represents a major unmet medical need with significant morbidity and mortality; familial amyloidotic polyneuropathy (FAP) affects approximately 10,000 people worldwide and familial amyloidotic cardiomyopathy (FAC) affects at least 40,000 people worldwide. FAP patients have a life expectancy of five to 15 years from symptom onset, and the only approved treatment options for early stage disease are liver transplantation, and tafamidis (approved in Europe). The mean survival for FAC patients is approximately 2.5 years, and there are no approved therapies. Senile systemic amyloidosis (SSA) is a non-hereditary form of TTR cardiac amyloidosis caused by idiopathic deposition of wild-type TTR; its prevalence is generally unknown, but is associated with advanced age. There is a significant need for novel therapeutics to treat patients with TTR amyloid polyneuropathy and/or cardiomyopathy.
Market News and Data brought to you by Benzinga APIs
Comments
Loading...
Posted In: NewsPress Releases
Benzinga simplifies the market for smarter investing

Trade confidently with insights and alerts from analyst ratings, free reports and breaking news that affects the stocks you care about.

Join Now: Free!