Alnylam Initiates Dosing in PNH Patients in Phase 1/2 Clinical Trial for ALN-CC5
Dec 17, 2015
- Company Expects to Report Initial Patient Data in Mid-2016 and Advance to Phase 3 Studies with ALN-CC5 in 2017 -
"Based on encouraging data recently presented at ASH, we've now advanced
ALN-CC5 into patients with PNH, where clinical activity can be measured
toward LDH, a key disease biomarker. If successful in lowering LDH
levels, we believe that ALN-CC5 could emerge as a differentiated
approach to address the continued unmet needs that exist for patients
with PNH and other complement mediated diseases," said
Clinical
data from the ongoing Phase 1/2 study were presented recently at the
- ALN-CC5 achieved up to 99 percent knockdown of serum C5 and up to 98 percent inhibition of serum sheep red blood cell hemolytic activity, an assay for complement activity;
- ALN-CC5 administration resulted in low levels of residual C5, which - based on comparisons from separate studies - were at or below the estimated levels of free C5 observed at therapeutic doses of eculizumab, an approved anti-C5 monoclonal antibody;
- The effects of ALN-CC5 were found to be highly durable, with C5 knockdown and complement inhibition results supporting a once monthly and possibly a once quarterly subcutaneous dose regimen; and
- Importantly, ALN-CC5 was shown to be generally well tolerated, with no clinically significant, drug-related adverse events to date.
ALN-CC5 Phase 1/2 Study Design
The ongoing Phase 1/2 trial
of ALN-CC5 is being conducted in three parts. Parts A and B are
randomized (3:1, drug:placebo), double-blind, placebo-controlled, SAD
and MAD studies, respectively, which enrolled up to a total of 60
healthy adult volunteers. These parts of the study were designed to
evaluate safety and tolerability of single and multiple subcutaneous
doses of ALN-CC5. Additional objectives include clinical activity as
measured by knockdown of serum C5 and levels of residual C5, and by
effects on inhibition of serum complement activity, including
measurements of CAP and CCP activity, as well as serum sheep red blood
cell hemolytic activity. A total of 5 SAD cohorts were enrolled in the
study, with fixed doses ranging from 50 to 900 mg. A total of 3 MAD
cohorts have been enrolled in the study with fixed doses of 100, 200 or
400 mg, where healthy adult volunteers are receiving once weekly,
subcutaneous doses of ALN-CC5 or placebo for 5 weeks. Part C is an
open-label, multi-dose study in approximately 16 patients with PNH, to
assess safety, tolerability, and clinical activity of ALN-CC5,
administered for up to 13 weeks. This part of the study will include an
exploratory evaluation of ALN-CC5 effects on levels of LDH, a measure of
endogenous red blood cell hemolysis.
About ALN-CC5
ALN-CC5 is an investigational RNAi therapeutic
targeting the C5 component of the complement pathway, currently in early
stage clinical development for the treatment of complement-mediated
diseases. The safety and efficacy of ALN-CC5 have not been evaluated by
the
In January 2014, Alnylam and Genzyme, a
Sanofi company, formed an alliance to accelerate and expand the
development and commercialization of RNAi therapeutics across the world.
The alliance is structured as a multi-product geographic alliance in the
field of rare diseases. Alnylam retains product rights in North
America and Western Europe, while Genzyme obtained the right to access
certain programs in Alnylam's current and future Genetic Medicines
pipeline, including ALN-CC5, in the rest of the world. In certain
defined instances, Genzyme has co-development/co-commercialization
and/or global product rights. Genzyme's rights are structured as an
opt-in that is triggered upon achievement of human proof-of-principle.
About RNAi
RNAi (RNA interference) is a revolution in
biology, representing a breakthrough in understanding how genes are
turned on and off in cells, and a completely new approach to drug
discovery and development. Its discovery has been heralded as "a major
scientific breakthrough that happens once every decade or so," and
represents one of the most promising and rapidly advancing frontiers in
biology and drug discovery today which was awarded the 2006 Nobel Prize
for Physiology or Medicine. RNAi is a natural process of gene silencing
that occurs in organisms ranging from plants to mammals. By harnessing
the natural biological process of RNAi occurring in our cells, the
creation of a major new class of medicines, known as RNAi therapeutics,
is on the horizon. Small interfering RNA (siRNA), the molecules that
mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target
the cause of diseases by potently silencing specific mRNAs, thereby
preventing disease-causing proteins from being made. RNAi therapeutics
have the potential to treat disease and help patients in a fundamentally
new way.
About
Alnylam is a biopharmaceutical
company developing novel therapeutics based on RNA interference, or
RNAi. The company is leading the translation of RNAi as a new class of
innovative medicines. Alnylam's pipeline of investigational RNAi
therapeutics is focused in 3 Strategic Therapeutic Areas (STArs):
Genetic Medicines, with a broad pipeline of RNAi therapeutics for the
treatment of rare diseases; Cardio-Metabolic Disease, with a pipeline of
RNAi therapeutics toward genetically validated, liver-expressed disease
targets for unmet needs in cardiovascular and metabolic diseases; and
Hepatic Infectious Disease, with a pipeline of RNAi therapeutics that
address the major global health challenges of hepatic infectious
diseases. In early 2015, Alnylam launched its "Alnylam 2020" guidance
for the advancement and commercialization of RNAi therapeutics as a
whole new class of innovative medicines. Specifically, by the end of
2020, Alnylam expects to achieve a company profile with 3 marketed
products, 10 RNAi therapeutic clinical programs - including 4 in late
stages of development - across its 3 STArs. The company's demonstrated
commitment to RNAi therapeutics has enabled it to form major alliances
with leading companies including
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 ALN-CC5, expectations
regarding the timing of clinical trials with ALN-CC5, including the
expected initiation of a Phase 3 trial in 2017, and the reporting of
clinical data from these trials, including the expected reporting of
additional data from its ongoing Phase 1/2 trial in mid-2016, its
expectations regarding its STAr pipeline growth strategy, and its plans
regarding 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 may differ materially from those indicated by these
forward-looking statements as a result of various important 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 drug 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, actions of
regulatory agencies, which may affect the initiation, timing and
progress of clinical trials, obtaining, maintaining and protecting
intellectual property, Alnylam's ability to enforce its patents against
infringers and defend its patent portfolio against challenges from third
parties, obtaining regulatory approval for products, competition from
others using technology similar to Alnylam's and others developing
products for similar uses, Alnylam's ability to manage operating
expenses, Alnylam's ability to 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, marketing, sales and distribution
of products, the outcome of litigation, 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 to update any forward-looking statements.
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