New, One-Year Data from ORION-1 Phase II Study of Inclisiran Extends Excellent Long-Term Efficacy and Safety Profile, Affirming Dose for Phase III Trials
-Inclisiran lowering effects on bad-cholesterol (LDL-C) are robust (mean 56% at Day-150; maximum 81%) and sustained (average 51% across a planned six-month dosing interval), with minimum intra-patient variability-
-Safety data for inclisiran from ORION-1 now include 370 subject-years of observation, including at least 300 subject-years of inclisiran effects; no material safety issues observed on inclisiran - similar to placebo-
-After nine months, with no further inclisiran treatment, LDL-C returns towards pre-treatment levels in a near-linear manner, enabling predictable dose-planning-
-One-year ORION-1 data reaffirm inclisiran's potential to address unmet needs with highly-differentiated, infrequent, low-volume, dosing regimen of two injections per year-
-Inclisiran Phase III development program gearing up-
-New, one-year data from ORION-1 study presented today at ESC 2017-
Following the presentation of primary results from ORION-1 at ACC.17 in
Efficacy data affirm inclisiran's significant LDL-C lowering effects
following a starting dose of 300 mg given on Day-1 and Day-90, after
which the mean LDL-C reduction was 56% at Day-150 and 51% at Day-180.
For the subsequent six-month period - from Day-90 to Day-270 - the
time-averaged LDL-C reduction was 51% with minimum intra-patient
variability over time (all comparisons to placebo P < 0.0001). These
robust data underscore the selection of a six monthly maintenance dose
of 300 mg in Phase III trials, which are now in advanced stages of
preparation. The Phase III LDL-C lowering trials in 3,500 patients,
which are designed to form the basis for inclisiran approval in
With completion of one-year follow-up, safety data for inclisiran from the Phase II ORION-1 study now include 370 subject-years of observation, including at least 300 subject-years of inclisiran effects. As in prior analyses, no material safety issues were observed on inclisiran, which continued to demonstrate an adverse event profile similar to placebo. There were no deaths or serious adverse events during the extended observation period. In particular, in spite of the prolonged LDL-C lowering effects of inclisiran, there were no investigational drug-related elevations of liver enzymes and no neuropathy, change in renal function, thrombocytopenia or anti-drug antibodies during extended follow-up, or at any earlier time periods in the ORION-1 study.
The extended observation also demonstrated that, after nine months, with no further inclisiran treatment, LDL-C returns towards pre-treatment levels in a near-linear manner. This observation also supports dose planning for further trials. One-year ORION-1 data reaffirm inclisiran's potential to address unmet needs with a highly-differentiated, infrequent, low-volume dosing regimen of two injections per year.
"The one-year results from ORION-1 re-affirm inclisiran's unique and
highly-differentiated attributes, and its game-changing potential to
address the unmet needs of millions of at-risk, often non-adherent,
patients worldwide who continue to struggle with high cholesterol given
the limitations of available therapies," said
ORION-1 Principal Investigator, Professor
Professor John JP Kastelein, Chairman of the ORION 1 study, and
Professor of Medicine, and Chairman of the
ORION-1 is a placebo-controlled, double-blind, randomized Phase II study of single or multiple subcutaneous injections of inclisiran in a total of 501 patients with atherosclerotic cardiovascular disease (ASCVD), or ASCVD-risk equivalents (e.g., diabetes and familial hypercholesterolemia), and elevated LDL-C despite maximum tolerated doses of LDL-C lowering therapies. The study compared the effect of different doses of inclisiran and evaluated the potential for an infrequent dosing regimen. The primary endpoint of the study was the percentage change in LDL-C from baseline at Day-180.
Inclisiran (formerly known as PCSK9si or ALN-PCSsc) is an investigational GalNAc-conjugated RNAi therapeutic targeting PCSK9 - a genetically validated protein regulator of LDL receptor metabolism - being developed for the treatment of hypercholesterolemia. In contrast to anti-PCSK9 monoclonal antibodies (MAbs) that bind to PCSK9 in blood, inclisiran is a first-in-class investigational medicine that acts by turning off PCSK9 synthesis in the liver.
About The Medicines Company
Alnylam (NASDAQ: ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of patients who have limited or inadequate treatment options. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust discovery platform and deep pipeline of investigational medicines, including three product candidates that are in late-stage development or will be in 2017. Looking forward, Alnylam will continue to execute on its "Alnylam 2020" strategy of building a multi-product, commercial-stage biopharmaceutical company with a sustainable pipeline of RNAi-based medicines. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on Twitter at @Alnylam.
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include the timing and success of a commercial launch of inclisiran in
Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, Alnylam's views with respect to the potential for RNAi therapeutics, including inclisiran, its expectations regarding the timing of clinical studies, its expectations regarding scientific and regulatory support for inclisiran, its expectations regarding its "Alnylam 2020" guidance for the advancement and commercialization of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, Alnylam's ability to discover and develop novel drug candidates and delivery approaches, successfully demonstrate the efficacy and safety of its product candidates, the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates for a specified indication or at all, actions or advice of regulatory agencies, which may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional pre-clinical and/or clinical testing, delays, interruptions or failures in the manufacture and supply of our product candidates, obtaining, maintaining and protecting intellectual property, Alnylam's ability to enforce its intellectual property rights against third parties and defend its patent portfolio against challenges from third parties, obtaining and maintaining regulatory approval, pricing and reimbursement for products, progress in establishing a commercial and ex-United States infrastructure, competition from others using technology similar to Alnylam's and others developing products for similar uses, Alnylam's ability to manage its growth and operating expenses, obtain additional funding to support its business activities, and establish and maintain strategic business alliances and new business initiatives, Alnylam's dependence on third parties for development, manufacture and distribution of products, the outcome of litigation, the risk of government investigations, and unexpected expenditures, as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.
The scientific information referenced in this news release relating to
inclisiran is preliminary and investigative. Inclisiran has not been
approved by the
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