– Plozasiran diminished triglycerides by 80% from baseline and diminished the danger of creating acute pancreatitis by 83%
– Related responses had been noticed in sufferers with genetically confirmed and clinically recognized FCS
– Based mostly on these findings, Arrowhead plans to file a New Drug Software by year-end 2024
– PALISADE outcomes concurrently printed in The New England Journal of Drugs
– 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) immediately 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 authorized remedies within the U.S. PALISADE efficiently met its main endpoint and all multiplicity-controlled key secondary endpoints, together with statistically important reductions in triglycerides (TGs), apolipoprotein C-III (APOC3), and the incidence of acute pancreatitis (AP). These information had been offered immediately in a late-breaking oral presentation on the European Society of Cardiology (ESC) Congress 2024 and concurrently printed in The New England Journal of Drugs.
Based mostly on these optimistic findings from the PALISADE research, Arrowhead intends to file a New Drug Software with the USA Meals and Drug Administration (FDA) by year-end 2024 and plans to hunt regulatory approval with extra international regulatory authorities thereafter.
Folks residing with extraordinarily excessive triglyceride ranges, like these within the PALISADE research, have a considerably increased threat of creating acute pancreatitis and related long-term sequelae, together with a poor high quality of life. There are at the moment no authorized therapies within the U.S. to particularly deal with FCS, in order physicians now we have only a few choices to assist our sufferers apart from varied triglyceride-lowering medicines which offer minimal profit, and really strict food plan restrictions that take a major toll on sufferers and their households, stated Gerald F. Watts, D.Sc., M.D., Ph.D., Winthrop Professor of Cardio-metabolic Drugs on the College of Western Australia, Perth. Plozasiran demonstrated very deep reductions in triglycerides within the PALISADE research and is the one investigational drugs to attain a statistically important discount within the threat of creating acute pancreatitis in sufferers with genetically confirmed and clinically recognized FCS in a managed research. These outcomes are encouraging and supply hope to folks residing with FCS and their physicians who’re in determined want of latest protected and efficient remedy 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 varied affected person populations, together with SHASTA in sufferers with extreme hypertriglyceridemia, MUIR in sufferers with blended hyperlipidemia, and now PALISADE in sufferers with FCS. Based mostly on the info generated thus far, we view plozasiran as probably best-in-class and supportive of growth throughout the spectrum of triglyceride issues. Particularly, immediately we confirmed that in PALISADE a excessive proportion of sufferers receiving plozasiran achieved triglyceride ranges under guideline-directed threat thresholds related to the danger of acute pancreatitis, which is a essential remedy aim that physicians talk to us continuously. Additional, PALISADE included sufferers with a longtime genetic prognosis of FCS and sufferers with symptomatic, persistent chylomicronemia suggestive of FCS. The consistency of leads to PALISADE means that plozasiran response could also be unbiased of the presence of recognized FCS-associated genetic variants. That is supportive of the potential worth of plozasiran in sufferers with clinically recognized illness, no matter genetic standing.
Choose PALISADE Outcomes
In PALISADE, 75 sufferers with persistent chylomicronemia, with or with out a genetic prognosis, had 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 recognized 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 threat thresholds related to acute pancreatitis occurred as early as one month after trial initiation and confirmed modest variation all through the 12-month blinded remedy interval. The imply share change in triglyceride degree was much like median values.
At month ten, APOC3 was considerably diminished 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 instances of acute pancreatitis that had been referred for adjudication, 9 episodes in seven sufferers had been positively adjudicated.
Plozasiran demonstrated statistical significance for this endpoint, with sufferers receiving plozasiran reaching an 83% discount within the threat of creating acute pancreatitis versus placebo. A complete of two instances occurred in two of fifty sufferers (4%) receiving plozasiran, and 7 instances 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 had been belly ache, COVID-19, nasopharyngitis, headache, nausea, again ache, higher respiratory tract an infection, and diarrhea. Hostile occasions among the many sufferers within the two plozasiran dose teams had been usually much like these within the placebo group. Extreme and severe opposed occasions had been extra widespread within the placebo group. Hyperglycemia was noticed in a restricted variety of sufferers within the remedy 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 Kind: Late Breaking Science
Slides from the late-breaking oral presentation at ESC 2024 could also be accessed on the Occasions and Displays web page within the Buyers 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 characteristic an encore presentation of the ESC 2024 information by Professor Watts and can embody dialogue by Arrowhead administration. To register for the occasion, please go to: https://lifescievents.com/occasion/arrowheadpharma/.
The dwell occasion and an archived webcast can also be accessed on the Occasions and Displays web page within the Buyers part of the Arrowhead web site.
About PALISADE Section 3 Examine
The PALISADE research (NCT05089084) is a Section 3 placebo managed research to guage the efficacy and security of plozasiran in adults with genetically confirmed or clinically recognized 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 international locations had been randomized to obtain 25 mg plozasiran, 50 mg plozasiran, or matching placebo as soon as each three months. Members who accomplished the randomized interval had been eligible to proceed in a 2-part extension interval, the place all contributors obtain plozasiran.
About Familial Chylomicronemia Syndrome
Familial chylomicronemia syndrome (FCS) is a extreme and uncommon genetic illness typically brought on by varied monogenic mutations. FCS results in extraordinarily excessive triglyceride (TG) ranges, sometimes over 880 mg/dL. Such extreme elevations can result in varied severe indicators and signs together with acute and probably deadly pancreatitis, power belly ache, diabetes, hepatic steatosis, and cognitive points. At present, the therapeutic choices that may adequately deal with FCS are restricted.
About Plozasiran
Plozasiran, beforehand referred to 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 remedy 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 remedy emergent opposed occasions reported that usually 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 Monitor 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 Software with the FDA in 2024 and plans to hunt regulatory approval with extra international regulatory authorities. Investigational plozasiran has not been reviewed or authorized to deal with any illness.
About Plozasiran EAP
Arrowhead is dedicated to bringing new investigational medicines to sufferers with severe illnesses as rapidly and effectively as attainable. The corporate has established an expanded entry program (EAP) for some people residing with FCS. As with all investigational drugs that has not been authorized by regulatory authorities, investigational plozasiran could or might not be efficient in treating your prognosis or situation, and there could also be dangers related to its use. If you’re a affected person or caregiver wishing to know extra about this plozasiran EAP for FCS, please focus on this EAP and all remedy choices together with your treating doctor. If you’re 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 illnesses 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 info, please go to www.arrowheadpharma.com, or comply with us on X (previously Twitter) at @ArrowheadPharma or on LinkedIn. To be added to the Firm’s electronic mail listing and obtain information straight, please go to http://ir.arrowheadpharma.com/email-alerts.
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Supply: Arrowhead Prescription drugs, Inc.
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Arrowhead Prescription drugs, Inc.
Vince Anzalone, CFA
626-304-3400
ir@arrowheadpharma.com
Buyers:
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.