Newborn Allenilam is a global leader in RNAi therapeutics, with two RNAi drugs (Onpattro, Givlaari) and two RNAi drugs (lumasiran and Novartic co-products inclisiran) currently under review by regulators, with several of their pipelines in the late clinical development phase.
recently, the company presented positive interim data for an ongoing Phase I study of the RNAi drug ARN-AGT at the American Heart Association (AHA) 2020 Scientific Meeting on November 13-17.
ALG-AGT is an RNAi therapy that is being developed to treat hypertension, a subdern injectable, liver-targeted angiotensin (AGT). A randomized, double-blind, placebo-controlled, single incremental dose (SAD) study, published at the
conference, is evaluating the safety, tolerance, and initial pharmacodynamics and pharmacodynamics of ALP-AGT in patients with mild or moderate hypertension.
the average age of the patients studied in the study was 52 years (35-65 years), with an average baseline of 24 hours of systolic pressure (SBP) and thud pressure (DBP) of 139 mmHg (mm-Hg) and 86 (SD-/-7) mmHg, respectively.
the study, patients were included in an incremental dose queue of 10 mg, 25 mg, 50 mg, 100 mg, and 200 mg doses of ALN-AGT (N-12/queue; ALN-AGT: placebo randomized grouping at a 2:1 scale).
the data released at the AHA meeting is September 16, 2020.
data showed that patients treated with ALN-AGT (the only prebium for all angiotrophosin peptides, including the powerful angiosent angiotrophosin II) showed reduced dose dependence compared to placebos.
in the 200mg dose queue, the average reduction in AGT at 8 weeks was 94.9 plus/-1.6%.
after a single dose of 100 or 200 mg, a reduction of >90% in serum AGT was observed for up to 12 weeks, of which AGT decreased by up to 97.6% at a dose of 200 mg.
a reduced persistence of AGT supports quarterly dosing, and may even be given at a lower frequency.
control of blood pressure (BP) is the most common risk factor for cardiovascular disease and the main cause of progression of chronic kidney disease.
In the Phase I study, a decrease in blood pressure was observed along with a decrease in serum AGT levels: a queue of 100 or 200 mg doses was received using data measured by Dynamic Blood Pressure Monitoring (ABPM) and an average 24-hour SBP drop of more than 10 mmHg was observed at the 8th week.
at a dose of 200 mg, the average BP decrease at week 8 was 11.0 plus/-2.4 mmHg for SBP and 7.7 plus/-1.1 mmHg for DBP.
the largest reductions observed in SBP and DBP were 19.0 mmHg and 12.3 mmHg, respectively.
research, ALN-AGT demonstrated good tolerance and acceptable safety, supporting further development.
Most adverse events (AEs) are mild or moderate in severity and can be resolved without intervention, with the most common adverse events including a mild and transient injection site reaction in 5 out of 40 patients treated with ALN-AGT (12.5%).
serum alanine transaminase (ALT), serum creatinine, or serum potassium had no clinically significant elevation, nor did patients need to intervene with hypotension.
treatment-related adverse events, deaths, or adverse events that led to withdrawal from the study occurred.
is a complex multi-factor disease clinically defined as SBP exceeding 130 mmHg or DBP exceeding 80 mmHg.
there has been a lack of innovation in the treatment of hypertension over the past few decades.
Despite the available antihypertensive drugs, about half of hypertension patients still have poor blood pressure control, so new treatments are urgently needed to improve patient compliance and to continuously control blood pressure during the interval between administrations.
ALN-AGT is a subsokin injection, AGT-targeted RNAi therapy used to treat high blood pressure in people with high medical needs.
AGT is the most upstream prelude to the nephrin-angiotensin-aldosterone system (RAAS), and RAAS is a cascading reaction that plays an important role in blood pressure regulation and inhibits RAAS has been shown to have a blood pressure-lowering effect.
alN-AGT inhibits the synthesis of AGT in the liver, leading to a sustained decrease in AGT proteins and angiotensin (Ang) II.
ALN-AGT uses Alnylam's proprietary Enhanced Stabilization Chemistry (ESC-plus) GalNAc association technology to make subdernation more selective and broader therapeutic index.
safety and effectiveness of ALN-AGT has not been evaluated by the FDA, EMA or any other regulatory agency.
ALT-AGT mechanism from the preliminary results of Phase I studies, supporting the potential of ALN-AGT as a new treatment for hypertension.
Blocking all sources of angiotensin peptides through RNAi-mediated AGT silence, ALN-AGT has the potential to prolong the effects of the drug, reduce the frequency of administration, and continuously lower blood pressure, which helps patients achieve and maintain their blood pressure goals, thereby reducing their risk of cardiovascular disease without having to take multiple medications every day.
"Hypertension is considered a changeable risk factor for cardiovascular disease and the leading cause of death and disability worldwide," commented Dr. Akshay Desai, director of the Cardiovascular Disease and Heart Failure Program at Harvard University's Bregan Women's Hospital and an associate professor at Harvard Medical School.
, although there are effective antihypertensive treatments, in clinical practice, according to the guidelines recommended blood pressure targets for treatment is still not ideal.
many factors may be the cause of this treatment gap, patients' high pill burden and inconsistent dependence on prescription therapies may play an important role.
interim results from phase I studies show that ALN-AGT can continuously reduce blood pressure for up to 3 months after a single subsopod injection, with dose dependence, which may provide a new way to ensure better treatment compliance and improved blood pressure control.
further study to determine the safety and clinical efficacy of this method is essential.
" article Reference Source: Alnylam Pharma's hypertension candidate show encouraged action in early-stage study Original title: RNAi therapy ALN-AGT single-drug treatment 8 weeks to reduce serum angiotensin levels by 95%, continuously lower blood pressure!