– Plozasiran lowered triglycerides by 80% from baseline and lowered the chance of creating acute pancreatitis by 83%
– Comparable responses have been noticed in sufferers with genetically confirmed and clinically identified FCS
– Primarily based on these findings, Arrowhead plans to file a New Drug Utility by year-end 2024
– PALISADE outcomes concurrently revealed in The New England Journal of Medication
– Firm internet hosting a digital analyst and investor occasion on September 3, 2024, at 8:00 am EDT to debate outcomes
PASADENA, Calif.–(BUSINESS WIRE)–Arrowhead Prescription drugs, Inc. (NASDAQ: ARWR) as we speak introduced outcomes from the Section 3 PALISADE research of investigational plozasiran in sufferers with familial chylomicronemia syndrome (FCS), a extreme and uncommon genetic illness which at the moment has no authorised remedies within the U.S. PALISADE efficiently met its major endpoint and all multiplicity-controlled key secondary endpoints, together with statistically vital reductions in triglycerides (TGs), apolipoprotein C-III (APOC3), and the incidence of acute pancreatitis (AP). These information have been introduced as we speak in a late-breaking oral presentation on the European Society of Cardiology (ESC) Congress 2024 and concurrently revealed in The New England Journal of Medication.
Primarily based on these constructive findings from the PALISADE research, Arrowhead intends to file a New Drug Utility with the USA Meals and Drug Administration (FDA) by year-end 2024 and plans to hunt regulatory approval with further world regulatory authorities thereafter.
Individuals residing with extraordinarily excessive triglyceride ranges, like these within the PALISADE research, have a considerably greater danger of creating acute pancreatitis and related long-term sequelae, together with a poor high quality of life. There are at the moment no authorised therapies within the U.S. to particularly deal with FCS, in order physicians now we have only a few choices to assist our sufferers aside from numerous triglyceride-lowering medicines which give minimal profit, and really strict eating regimen restrictions that take a big toll on sufferers and their households, stated Gerald F. Watts, D.Sc., M.D., Ph.D., Winthrop Professor of Cardio-metabolic Medication on the College of Western Australia, Perth. Plozasiran demonstrated very deep reductions in triglycerides within the PALISADE research and is the one investigational medication to attain a statistically vital discount within the danger of creating acute pancreatitis in sufferers with genetically confirmed and clinically identified FCS in a managed research. These outcomes are encouraging and provide hope to individuals residing with FCS and their physicians who’re in determined want of latest secure and efficient therapy choices.
Bruce Given, M.D., chief medical scientist at Arrowhead, added, We proceed to be impressed by the promising outcomes from the SUMMIT program of scientific research of plozasiran in numerous affected person populations, together with SHASTA in sufferers with extreme hypertriglyceridemia, MUIR in sufferers with blended hyperlipidemia, and now PALISADE in sufferers with FCS. Primarily based on the info generated thus far, we view plozasiran as doubtlessly best-in-class and supportive of improvement throughout the spectrum of triglyceride problems. Particularly, as we speak we confirmed that in PALISADE a excessive proportion of sufferers receiving plozasiran achieved triglyceride ranges under guideline-directed danger thresholds related to the chance of acute pancreatitis, which is a crucial therapy aim that physicians talk to us often. Additional, PALISADE included sufferers with a longtime genetic analysis of FCS and sufferers with symptomatic, persistent chylomicronemia suggestive of FCS. The consistency of ends in PALISADE means that plozasiran response could also be impartial of the presence of recognized FCS-associated genetic variants. That is supportive of the potential worth of plozasiran in sufferers with clinically identified illness, no matter genetic standing.
Choose PALISADE Outcomes
In PALISADE, 75 sufferers with persistent chylomicronemia, with or and not using a genetic analysis, have been randomly assigned to obtain subcutaneous plozasiran at 25 mg (n=26) or 50 mg (n=24) or placebo (n=25) each three months for 12 months. At baseline, the median triglyceride degree was 2044 mg/dL. Forty-four sufferers (59%) had genetically confirmed FCS and 31 sufferers (41%) had clinically identified persistent chylomicronemia suggestive of FCS.
At month ten, the median discount from baseline within the fasting triglyceride degree (the first endpoint) was -80% within the 25 mg plozasiran group, -78% within the 50 mg plozasiran group, and -17% within the placebo group (p
Marked reductions within the median triglyceride degree under guideline-directed danger thresholds related to acute pancreatitis occurred as early as one month after trial initiation and confirmed modest variation all through the 12-month blinded therapy interval. The imply share change in triglyceride degree was much like median values.
At month ten, APOC3 was considerably lowered with median reductions of -93% within the 25 mg plozasiran group, -96% within the 50 mg plozasiran group, and -1% within the placebo group (p
The ultimate alpha-controlled secondary efficacy finish level in contrast the incidence of positively adjudicated acute pancreatitis in a pre-specified pooled evaluation of the 25 mg and the 50 mg plozasiran teams versus the pooled placebo group. Among the many 38 suspected circumstances of acute pancreatitis that have been referred for adjudication, 9 episodes in seven sufferers have been positively adjudicated.
Plozasiran demonstrated statistical significance for this endpoint, with sufferers receiving plozasiran reaching an 83% discount within the danger of creating acute pancreatitis versus placebo. A complete of two circumstances occurred in two of fifty sufferers (4%) receiving plozasiran, and 7 circumstances occurred in 5 of 25 sufferers (20%) receiving placebo (odds ratio, 0.17, p=0.03).
Security and Tolerability
Plozasiran demonstrated a positive security profile within the PALISADE research. The commonest opposed occasions have been stomach ache, COVID-19, nasopharyngitis, headache, nausea, again ache, higher respiratory tract an infection, and diarrhea. Opposed occasions among the many sufferers within the two plozasiran dose teams have been typically much like these within the placebo group. Extreme and critical opposed occasions have been extra widespread within the placebo group. Hyperglycemia was noticed in a restricted variety of sufferers within the therapy teams however was confined to sufferers with pre-diabetes and diabetes.
ESC 2024 Presentation Particulars
A Randomised, Placebo-Managed Section 3 Examine of Plozasiran in Sufferers with Familial Chylomicronemia Syndrome
Date/Time: September 2, 2024, 11:36 am BST
Presenter: Professor Gerald Watts, College of Western Australia
Session: Small trials, trial updates, and different research on lipid remedy
Session Sort: Late Breaking Science
Slides from the late-breaking oral presentation at ESC 2024 could also be accessed on the Occasions and Shows web page within the Traders part of the Arrowhead web site after the oral presentation concludes.
Digital Analyst and Investor Occasion
The analyst and investor occasion on September 3, 2024, at 8:00 am EDT will function an encore presentation of the ESC 2024 information by Professor Watts and can embrace dialogue by Arrowhead administration. To register for the occasion, please go to: https://lifescievents.com/occasion/arrowheadpharma/.
The stay occasion and an archived webcast can also be accessed on the Occasions and Shows web page within the Traders part of the Arrowhead web site.
About PALISADE Section 3 Examine
The PALISADE research (NCT05089084) is a Section 3 placebo managed research to judge the efficacy and security of plozasiran in adults with genetically confirmed or clinically identified FCS. The first endpoint of the research is p.c change from baseline in fasting TG versus placebo at Month 10. A complete of 75 topics distributed throughout 39 totally different websites in 18 nations have been randomized to obtain 25 mg plozasiran, 50 mg plozasiran, or matching placebo as soon as each three months. Contributors who accomplished the randomized interval have been eligible to proceed in a 2-part extension interval, the place all individuals obtain plozasiran.
About Familial Chylomicronemia Syndrome
Familial chylomicronemia syndrome (FCS) is a extreme and uncommon genetic illness usually brought on by numerous monogenic mutations. FCS results in extraordinarily excessive triglyceride (TG) ranges, usually over 880 mg/dL. Such extreme elevations can result in numerous critical indicators and signs together with acute and doubtlessly deadly pancreatitis, persistent stomach ache, diabetes, hepatic steatosis, and cognitive points. At the moment, the therapeutic choices that may adequately deal with FCS are restricted.
About Plozasiran
Plozasiran, beforehand known as ARO-APOC3, is a first-in-class investigational RNA interference (RNAi) therapeutic designed to cut back manufacturing of apolipoprotein C-III (APOC3) which is a element of triglyceride wealthy lipoproteins (TRLs) and a key regulator of triglyceride metabolism. APOC3 will increase triglyceride ranges within the blood by inhibiting breakdown of TRLs by lipoprotein lipase and uptake of TRL remnants by hepatic receptors within the liver. The aim of therapy with plozasiran is to cut back the extent of APOC3, thereby decreasing triglycerides and restoring lipids to extra regular ranges.
In a number of scientific research, investigational plozasiran demonstrated reductions in triglycerides and a number of atherogenic lipoproteins in sufferers with familial chylomicronemia syndrome (FCS), extreme hypertriglyceridemia (SHTG), and blended hyperlipidemia. Plozasiran has demonstrated a positive security profile thus far with therapy emergent opposed occasions reported that typically replicate the comorbidities and underlying circumstances of the research populations.
Plozasiran is being investigated within the SUMMIT program of scientific research, together with the PALISADE Section 3 research in sufferers with FCS, which not too long ago accomplished, the SHASTA research in sufferers with SHTG, and the MUIR and CAPITAN research in sufferers with blended hyperlipidemia.
Plozasiran has been granted Orphan Drug Designation and Quick Observe Designation by the U.S. Meals and Drug Administration and Orphan Drug Designation by the European Medicines Company. Arrowhead intends to file a New Drug Utility with the FDA in 2024 and plans to hunt regulatory approval with further world regulatory authorities. Investigational plozasiran has not been reviewed or authorised to deal with any illness.
About Plozasiran EAP
Arrowhead is dedicated to bringing new investigational medicines to sufferers with critical ailments as rapidly and effectively as potential. The corporate has established an expanded entry program (EAP) for some people residing with FCS. As with all investigational medication that has not been authorised by regulatory authorities, investigational plozasiran could or is probably not efficient in treating your analysis or situation, and there could also be dangers related to its use. In case you are a affected person or caregiver wishing to know extra about this plozasiran EAP for FCS, please talk about this EAP and all therapy choices along with your treating doctor. In case you are a treating doctor and are searching for details about the plozasiran EAP or wish to request entry for a affected person, please contact EAP@arrowheadpharma.com.
About Arrowhead Prescription drugs (NASDAQ:)
Arrowhead Prescription drugs develops medicines that deal with intractable ailments by silencing the genes that trigger them. Utilizing a broad portfolio of RNA chemistries and environment friendly modes of supply, Arrowhead therapies set off the RNA interference mechanism to induce fast, deep, and sturdy knockdown of goal genes. RNA interference, or RNAi, is a mechanism current in residing cells that inhibits the expression of a selected gene, thereby affecting the manufacturing of a selected protein. Arrowhead’s RNAi-based therapeutics leverage this pure pathway of gene silencing.
For extra data, please go to www.arrowheadpharma.com, or observe us on X (previously Twitter) at @ArrowheadPharma or on LinkedIn. To be added to the Firm’s e mail checklist and obtain information immediately, please go to http://ir.arrowheadpharma.com/email-alerts.
Protected Harbor Assertion beneath the Personal Securities Litigation Reform Act:
This information launch accommodates forward-looking statements inside the which means of the “safe harbor” provisions of the Personal Securities Litigation Reform Act of 1995. Any statements contained on this launch aside from historic data could also be deemed to be forward-looking statements. With out limiting the generality of the foregoing, phrases similar to could, will, count on, imagine, anticipate, hope, intend, plan, challenge, may, estimate, proceed, goal, forecast or proceed or the destructive of those phrases or different variations thereof or comparable terminology are meant to determine such forward-looking statements. As well as, any statements that seek advice from projections of our future monetary efficiency, developments in our enterprise, expectations for our product pipeline or product candidates, together with anticipated regulatory submissions and scientific program outcomes, prospects or advantages of our collaborations with different firms, or different characterizations of future occasions or circumstances are forward-looking statements. These forward-looking statements embrace, however usually are not restricted to, statements in regards to the initiation, timing, progress and outcomes of our preclinical research and scientific trials, and our analysis and improvement applications; our expectations relating to the potential advantages of the partnership, licensing and/or collaboration preparations and different strategic preparations and transactions now we have entered into or could enter into sooner or later; our beliefs and expectations relating to milestone, royalty or different funds that might be attributable to or from third events beneath present agreements; and our estimates relating to future revenues, analysis and improvement bills, capital necessities and funds to 3rd events. These statements are primarily based upon our present expectations and communicate solely as of the date hereof. Our precise outcomes could differ materially and adversely from these expressed in any forward-looking statements on account of quite a few components and uncertainties, together with the influence of the continuing COVID-19 pandemic on our enterprise, the security and efficacy of our product candidates, selections of regulatory authorities and the timing thereof, the length and influence of regulatory delays in our scientific applications, our potential to finance our operations, the probability and timing of the receipt of future milestone and licensing charges, the long run success of our scientific research, our potential to efficiently develop and commercialize drug candidates, the timing for beginning and finishing scientific trials, fast technological change in our markets, the enforcement of our mental property rights, and the opposite dangers and uncertainties described in our most up-to-date Annual Report on Type 10-Okay, subsequent Quarterly Studies on Type 10-Q and different paperwork filed with the Securities and Change Fee sometimes. We assume no obligation to replace or revise forward-looking statements to replicate new occasions or circumstances.
Supply: Arrowhead Prescription drugs, Inc.
View supply model on businesswire.com: https://www.businesswire.com/information/dwelling/20240902885250/en/
Arrowhead Prescription drugs, Inc.
Vince Anzalone, CFA
626-304-3400
ir@arrowheadpharma.com
Traders:
LifeSci Advisors, LLC
Brian Ritchie
212-915-2578
britchie@lifesciadvisors.com
Media:
LifeSci Communications, LLC
Kendy Guarinoni, Ph.D.
724-910-9389
kguarinoni@lifescicomms.com
Supply: Arrowhead Prescription drugs, Inc.
