A single dose of Nucresiran 300mg or higher produced a rapid knockout of mean TTR levels of more than 90% by day 15 that was sustained for six months.
At these doses, a peak reduction of more than 96% in mean TTR levels was achieved by day 29.
Data support the potential for biannual or annual subcutaneous dosing, ATTR represents a new paradigm in the treatment of amyloidosis.
‘Encouraging safety and tolerability observed’
Alnylam continues to expect to share Phase 3 development projects in Q1 2025.
CAMBRIDGE, Mass.–( BUSINESS WIRE )–Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced the presentation of new results from its Phase 1 study Nucrecerin (formerly ALN-TTRsc04). Next-generation RNAi therapy in development for the treatment of transthyretin (ATTR) amyloidosis. The data were presented in an oral session at the American Heart Association Scientific Sessions 2024 in Chicago.
These new results showed that a single dose of nucreserin at 300 mg or higher led to a rapid knockdown of serum TTR with low inter-patient variability, with an average of 90% of the baseline achieved on day 15. Lack of excess and maintained for at least 180 days. At these doses, a greater than 96% reduction in mean TTR levels by day was achieved. 29. Furthermore, serum TTR levels remained substantially lower at 360 days with an average reduction of more than 70% after a single dose of 300 mg. Day 360 results are not yet available for the 600 mg and 900 mg dose groups. All doses of nucresiran have been well tolerated to date.
We are very excited by these new Phase 1 data with nucresiran, our next-generation TTR-targeting RNAi therapy, which showed that a single dose of ‰¥300 mg reduced TTR by 90% from day 15. Knocked out faster than % that sustained. At least six months, said Pushkal Garg, MD, chief Medical (TASE:) Officer, Alnelam. Additionally, we are encouraged by the ability of nucleocerin to reduce inter-patient variability in reducing TTR. Nucresiran utilizes our IKARIA platform, which has now demonstrated the ability to achieve durability in support of biennial or annual dosing, representing a potential new paradigm in the treatment of ATTR amyloidosis. Importantly, nucrecerin has been well tolerated at all dose levels tested to date. We look forward to sharing development plans for Phase 3 in the first quarter of 2025.
An ongoing phase 1 dose-finding study evaluated the safety of single doses of nucrecerin as well as the pharmacodynamics and pharmacokinetics in healthy subjects. As previously presented at Alnilam’s R&D Day in December 2023, a single dose of nucreserin led to a rapid knockdown of serum TTR that was highly durable.
In subjects receiving a single 300 mg dose of nucreserin, a 90.3% reduction in serum TTR was observed on day 15, 96.5% on day 29, and 92.6% on day 180. On day 360, an average reduction of 71.12% in serum TTR was observed. In subjects receiving a single dose of 600 mg, a 95.0% reduction in serum TTR was observed on day 15, 97.8% on day 29, and 96.0% on day 180. 15% was observed at day 29, 96.7% at day 29, and 94.2% at day 180. As of the data cutoff date, TTR knockdown levels at day 360 were not available for the 600 mg or 900 mg cohort.
There has been less variability between patients in TTR reduction. On day 29, TTR decreased from 96.0 to “96.7% in the 300 mg group, 96.6 to 98.6% in the 600 mg group, and 96.0 – 97.3% in the 900 mg group.
In the study, nucresiran was well tolerated at all doses tested. Most adverse events with doses are mild and none are considered treatment-related. No injection site reactions and no safety signals, including any liver-related signals, have been identified.
Phase 1 study design
The Phase 1 trial is a randomized, double-blind, placebo-controlled, single-escalation-dose study designed to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of nucrecerin in healthy adults. has gone The study enrolled 48 healthy adult subjects randomized 3:1 to receive an ascending dose of 5, 25, 100, 300, 600, or 900 mg of nucreserin or placebo. The primary endpoint of the study is safety and secondary endpoints include change from baseline in serum TTR over time, as well as the plasma and urinary pharmacokinetics (PK) characteristics of nucreserin.
About Nucresiran
Nucreserin is an investigational RNAi therapy to rapidly knock out mutant and wild-type transthyretin (TTR) and address the underlying cause of transthyretin (ATTR) amyloidosis. As part of Alnylam’s proprietary IKARIA™ platform, nucresiran has the potential to achieve deeper and more sustained rapid knockdown of TTR, allowing for less frequent dosing. The safety and efficacy of nucresiran have not been established or evaluated by the FDA, EMA or any other health authority.
About ATTR
Transthyretin amyloidosis (ATTR) is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by misfolded transthyretin (TTR) protein, which accumulates in various parts of the body, including the nerves, heart, and gastrointestinal tract. Accumulates as amyloid deposits. Patients may present with polyneuropathy, cardiomyopathy or both manifestations of the disease. There are two different forms of ATTR, “heritable ATTR (hATTR), which is caused by a variant of the TTR gene and affects approximately 50,000 people worldwide, and wild-type ATTR (wtATTR), which is caused by a variant of the TTR gene. It occurs without a variant and affects an estimated 200,000-300,000 people worldwide.
About RNAi
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. His discovery has been hailed as a major scientific breakthrough that happens once every decade or so, and was recognized with the 2006 Nobel Prize in Physiology or Medicine. By harnessing the natural biological process of RNAi found in our cells, a new class of drugs known as RNAi therapies is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, work by potently silencing messenger RNA (mRNA) at the forefront of today’s drugs. are “genetic precursors that encode disease-causing or disease-pathway proteins”. from being made. This is a revolutionary approach that has the potential to transform the care of patients with genetic and other diseases.
about Alnelam Pharmaceuticals (Nasdaq:)
Alnylam (Nasdaq: ALNY) has led the way in translating RNA interference (RNAi) into an entirely new class of innovative medicines with the potential to transform the lives of people with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapy represents a powerful, clinically validated approach to transformative medicine. Since its founding in 2002, Alnylam has led the RNAi revolution and continues to deliver a bold vision to turn scientific possibility into reality. Alnelam has a deep pipeline of investigational drugs, including several product candidates in late-stage development. Alnylam is pursuing its Alnylam P5x25 strategy to provide transformative medicines for both rare and common diseases that benefit patients worldwide through sustainable innovation and exceptional financial performance, resulting in a biotech profile. One has to be a leader. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and X (formerly Twitter) @Alnylam, or connect with us on LinkedIn, Facebook (NASDAQ:), or Instagram I’m busy.
Alnylam Forward-Looking Statements
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact relate to Al Neelam’s expectations, beliefs, goals, plans or prospects. including, without limitation, the ability for nucresiran to achieve two-year supportive durability or annual dosing and represent a new paradigm in the treatment of ATTR amyloidosis; ability to reduce inter-patient variability in reducing TTR with nucreserin; and the timing of the release of Alnelam’s Phase 3 development plans for Nukrisiran should be considered forward-looking statements. Actual results and future plans may differ materially from those expressed in these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, risks and uncertainties. : Alnylam’s ability to successfully implement its Alnylam P5x25. Strategy Alnylam’s ability to successfully demonstrate the efficacy and safety of its product candidates; preclinical and clinical results for Alnylam’s product candidates; actions or advice from regulatory agencies and Alnylam’s ability to obtain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; to successfully launch, market and sell Alnelam’s approved products globally; and any delays, interruptions or failures in the development and delivery of Alnylam’s product candidates or its marketed products; These risks are also discussed more fully in the Risk Factors of Alnylam’s 2023 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as follows: Alnylam’s subsequent quarterly reports on Form 10 may be updated from time to time. -Q and in its other SEC filings. Furthermore, any forward-looking statements represent Al Neelam’s views as of today only and should not be relied upon as representing its views as of any subsequent date. Alnylam expressly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.
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Alnylam Pharmaceuticals, Inc.
Christine Regan Lindenbaum
(Investors and Media)
+1-617-682-4340
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(Investor)
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Source: Alnylam Pharmaceuticals, Inc.
