By David Bautz, PhD
READ THE FULL ARWR RESEARCH REPORT
Enterprise Replace
Part 3 PALISADE Outcomes Revealed in The New England Journal of Drugs
On September 2, 2024, Arrowhead Prescribed drugs, Inc. (NASDAQ:ARWR) introduced outcomes for the Part 3 PALISADE trial of plozasiran in sufferers with familial chylomicronemia syndrome (FCS). The outcomes had been offered in a late-breaking oral presentation on the European Society of Cardiology (ESC) Congress 2024 and in addition revealed in The New England Journal of Drugs (Watts et al., 2024). The corporate held an investor name on September 3, 2024 and the slides for it may be discovered right here. Plozasiran was additionally lately granted Breakthrough Remedy designation by the U.S. FDA. It beforehand obtained Orphan Drug Designation and Quick Observe Designation by the FDA together with Orphan Drug Designation by the European Medicines Company.
The PALISADE trial enrolled 75 sufferers with persistent chylomicronemia, with or and not using a genetic prognosis of FCS, who had been randomized to subcutaneous plozasiran at 25 mg (n=26), 50 mg (n=24), or placebo (n=25) each three months for 12 months. Inclusion standards included a historical past of a number of triglyceride (TG) measurements above 1000 mg/dL (11.3 mmol/L) together with not less than one of many following: prior genetic testing prognosis for FCS; recurrent episodes of acute pancreatitis; recurrent hospitalizations for extreme belly ache with out different explainable trigger; historical past of childhood pancreatitis; or household historical past of HTG-induced acute pancreatitis. The next desk exhibits the baseline traits for the sufferers, together with the median baseline TG degree of 2044 mg/dL throughout all cohorts.
The next graphs present the median discount in triglycerides and degree of APOC3. On the ten-month time level, the median discount in fasting triglycerides was -80% within the 25 mg cohort, -78% within the 50 mg cohort, and -17% for the placebo cohort (P<0.001). The discount in APOC3 was -93% within the 25 mg cohort, -96% within the 50 mg cohort, and -1% within the placebo group (P<0.001).
An vital secondary efficacy endpoint in contrast the incidence of positively adjudicated acute pancreatitis (AP) in a pre-specified pooled evaluation of the 25 mg and 50 mg plozasiran teams versus the pooled placebo group. Of the 38 suspected instances of acute pancreatitis that had been referred for adjudication, 9 episodes in seven sufferers had been positively adjudicated. The outcomes confirmed an 83% discount within the danger of creating acute pancreatitis for plozasiran-treated sufferers in comparison with these handled with placebo. A complete of two instances occurred in two of fifty sufferers (4%) receiving plozasiran versus seven instances that occurred in 5 of 25 sufferers (20%) receiving placebo (OR 0.17; P=0.03).
The next desk supplies the abstract of hostile occasions throughout the trial. There was the next charge of significant or extreme hostile occasions within the placebo group, no adjustments had been seen in platelet counts, and there have been no deaths reported within the research.
Comparability with Olezarsen
Ionis Prescribed drugs is creating olezarsen, an antisense oligonucleotide that targets APOC3. Ionis lately reported that the NDA for olezarsen for the therapy of FCS was accepted for Precedence Evaluation with a PDUFA date of December 19, 2024. The outcomes from the Part 3 BALANCE trial of olezarsen in FCS had been lately revealed in The New England Journal of Drugs (Stroes et al., 2024). Whereas tough to carry out cross-trial comparisons, the next chart supplies a number of the parameters and outcomes for the Part 3 trials for olezarsen and plozasiran.
A number of factors that we predict are worthwhile for traders to think about embody:
• Olezarsen is dosed as soon as each 4 weeks whereas plozasiran is dosed as soon as each three months
• The entire topics within the olezarsen research had genetically confirmed FCS, whereas between one-half to two-thirds of topics within the plozasiran trial had generically confirmed FCS
• The triglyceride and APOC3 reductions had been higher for plozasiran than for olezarsen (with the caveat of median vs. imply values reported), with much less variability over time for plozasiran than for olezarsen.
• Plozasiran confirmed a statistically important lower within the danger of creating acute pancreatitis (AP), nonetheless the olezarsen trial was not powered for statistical significance however nonetheless confirmed a good charge ratio.
Total, we imagine the plozasiran outcomes are extremely aggressive and will place the product to do nicely within the FCS market.
Conclusion
The outcomes from the Part 3 PALISADE trial of plozasiran in FCS are very encouraging and we imagine the drug compares fairly favorably to olezarsen, which has a PDUFA date of December 19, 2024 for FCS. We look ahead to the corporate submitting the NDA for plozasiran and extra data on plans for its potential business launch subsequent 12 months. With no adjustments to our mannequin our valuation stays at $70 per share.
SUBSCRIBE TO ZACKS SMALL CAP RESEARCH to obtain our articles and stories emailed on to you every morning. Please go to our web site for added data on Zacks SCR.
DISCLOSURE: Zacks SCR has obtained compensation from the issuer straight, from an funding supervisor, or from an investor relations consulting agency, engaged by the issuer, for offering analysis protection for a interval of a minimum of one 12 months. Analysis articles, as seen right here, are a part of the service Zacks SCR supplies and Zacks SCR receives quarterly funds totaling a most price of as much as $40,000 yearly for these companies supplied to or concerning the issuer. Full Disclaimer HERE.
