Arrowhead Pharmaceuticals Reports Successful Topline Results for Plozasiran from the Pivotal Phase 3 PALISADE Study in Patients with Familial Chylomicronemia Syndrome
Arrowhead Pharmaceuticals (NASDAQ: ARWR) announced successful topline results from the Phase 3 PALISADE study of plozasiran, an investigational RNAi-based therapy for familial chylomicronemia syndrome (FCS).
The study achieved its primary endpoint with an 80% median reduction in triglycerides and secondary endpoints, including a reduction in acute pancreatitis incidents versus placebo. Additionally, mean reductions in APOC3 reached up to 94% at month 10.
Plozasiran demonstrated a favorable safety profile with fewer severe adverse events compared to placebo. Arrowhead plans to discuss these results at their June 25, 2024 Cardiometabolic event and is preparing to engage with regulatory authorities for a New Drug Application.
- Plozasiran achieved up to 80% median reduction in triglycerides, surpassing the primary endpoint.
- Mean reductions in APOC3 were up to 94% by month 10.
- Statistically significant reduction in acute pancreatitis incidents versus placebo.
- Favorable safety profile with fewer severe adverse events compared to placebo.
- Plans to file a New Drug Application with the FDA.
- Arrowhead will present full results at upcoming medical conferences and highlight data at their June 2024 Cardiometabolic event.
- Validation of Arrowhead's investigational RNAi-based therapy in a Phase 3 study.
- No FDA-approved therapies exist for FCS, indicating high risk and uncertainty for future regulatory approval.
- Potential treatment emergent adverse events, although fewer than placebo.
Insights
The topline results from the Phase 3 PALISADE study are a significant landmark for Arrowhead Pharmaceuticals and the cardiometabolic therapeutic area. Plozasiran demonstrated substantial efficacy in reducing triglycerides—with median reductions up to
RNA interference (RNAi) therapies like plozasiran represent a new frontier in the treatment of genetic and metabolic disorders and the success of this drug could pave the way for similar treatments in the future. However, while these results are promising, it is important to await the full dataset and any potential concerns that the regulatory bodies might raise. The favorable safety profile observed in this study, with severe adverse events being less common in the plozasiran group than in the placebo group, further supports the potential of this therapy. Yet, long-term safety and efficacy data will be essential to confirm these initial findings.
From a financial perspective, the successful Phase 3 results for plozasiran add substantial value to Arrowhead Pharmaceuticals' portfolio. Meeting both primary and key secondary endpoints not only strengthens the case for an FDA approval but also enhances investor confidence. The statistically significant reduction in triglycerides and incidence of acute pancreatitis will likely attract attention from stakeholders, potentially increasing the stock value in the short term.
Arrowhead's strategic move to position plozasiran as a top-tier option for multiple cardiometabolic diseases broadens its market reach beyond FCS, which could translate into considerable revenue streams. Nonetheless, investors should be cautious about the lengthy and costly drug approval process that lies ahead. The company's intention to discuss filings with the FDA and engage in Phase 3 studies for other populations are positive signs, but they also come with associated risks and expenses.
Another noteworthy aspect is the company's ability to mitigate the commonality of severe adverse events often seen with new drugs. This aspect, combined with robust efficacy data, may ease regulatory approvals and market adoption hurdles. However, market competition and healthcare reimbursement policies are factors that investors should continually monitor.
- Plozasiran achieved statistically significant median reductions in triglycerides up to
- Plozasiran achieved a statistically significant reduction in incidence of acute pancreatitis versus placebo
- Plozasiran is the company’s first investigational RNAi-based therapy to show clinical efficacy in a Phase 3 study
- Arrowhead plans to highlight recent data for its cardiometabolic pipeline at its June 25, 2024, Cardiometabolic event as part of the 2024 Summer Series of R&D Webinars
“The strong results from the Phase 3 PALISADE study, evaluating plozasiran in patients with FCS, significantly build upon the promising results from the Phase 2 SHASTA-2 and MUIR studies in patients with severe hypertriglyceridemia and mixed hyperlipidemia, recently published in JAMA Cardiology and the New England Journal of Medicine. These findings highlight the potential of plozasiran as a promising therapy for patients with various cardiometabolic disorders,” said Bruce Given, M.D., chief medical scientist at Arrowhead. “We look forward to discussing results at our June 25th Cardiometabolic event as part of our 2024 Summer Series of R&D Webinars and presenting the full PALISADE data at upcoming medical conferences.”
The primary endpoint for the PALISADE study was placebo adjusted median change in triglycerides at Month 10. At that timepoint, patients treated with quarterly doses of 25 and 50 mg plozasiran achieved median triglyceride reductions of -
In addition to meeting the primary endpoint, plozasiran met all key secondary endpoints and demonstrated statistical significance versus placebo.
There were 4 multiplicity-controlled key secondary endpoints: 1) percent change from baseline at Months 10 and 12 (averaged) in fasting triglycerides; 2) percent change from baseline at Month 10 in fasting APOC3; 3) percent change from baseline at Month 12 in fasting APOC3; 4) incidence of positively adjudicated events of acute pancreatitis during the randomized period.
Plozasiran demonstrated a favorable safety profile in the PALISADE study. The number of subjects reporting treatment emergent adverse events (AEs) were similar in plozasiran and placebo groups. Severe and serious AEs were less common with plozasiran than with placebo. The most common AEs reported were abdominal pain, COVID-19, nasopharyngitis, headache and nausea.
Christopher Anzalone, Ph.D., president and CEO at Arrowhead, added, “We see plozasiran data as best in class and with the potential to address multiple cardiometabolic diseases with substantial unmet need. We will now communicate the results to the FDA and discuss filing a New Drug Application for FCS. We will also continue to advance multiple additional Phase 3 studies for other patient populations. It is gratifying to see one of our investigational RNAi-based medicines get potentially closer to the patients who need it most. This moment represents validation of all the hard work from so many talented Arrowhead employees, our collaborators, and the FCS community over the years. We would like to express our sincere gratitude to the patients, caregivers, investigators, and study teams involved in the PALISADE study.”
Arrowhead plans to highlight recent data for its cardiometabolic pipeline at its June 25, 2024, Cardiometabolic event as part of the 2024 Summer Series of R&D Webinars. The company also plans to present full results from the Phase 3 PALISADE study at upcoming medical congresses and will begin to engage with global regulatory authorities about these data.
About PALISADE Phase 3 Study
The PALISADE study (NCT05089084) is a Phase 3 placebo controlled study to evaluate the efficacy and safety of plozasiran in adults with genetically confirmed or clinically diagnosed FCS. The primary endpoint of the study is percent change from baseline in fasting TG versus placebo at Month 10. A total of 75 subjects distributed across 39 different sites in 18 countries were randomized to receive 25 mg plozasiran, 50 mg plozasiran, or matching placebo once every three months. Participants who completed the randomized period were eligible to continue in a 2-part extension period, where all participants receive plozasiran.
About Familial Chylomicronemia Syndrome
Familial chylomicronemia syndrome (FCS) is a severe and ultrarare genetic disease often caused by various monogenic mutations. FCS leads to extremely high triglyceride (TG) levels, typically over 880 mg/dL. Such severe elevations can lead to various serious signs and symptoms including acute and potentially fatal pancreatitis, chronic abdominal pain, diabetes, hepatic steatosis, and cognitive issues. Currently, the therapeutic options that can adequately treat FCS are limited.
About Plozasiran
Plozasiran, previously called ARO-APOC3, is a first-in-class investigational RNA interference (RNAi) therapeutic designed to reduce production of Apolipoprotein C-III (APOC3) which is a component of triglyceride rich lipoproteins (TRLs) and a key regulator of triglyceride metabolism. APOC3 increases triglyceride levels in the blood by inhibiting breakdown of TRLs by lipoprotein lipase and uptake of TRL remnants by hepatic receptors in the liver. The goal of treatment with plozasiran is to reduce the level of APOC3, thereby reducing triglycerides and restoring lipids to more normal levels.
In multiple clinical studies, investigational plozasiran demonstrated reductions in triglycerides and multiple atherogenic lipoproteins in patients with familial chylomicronemia syndrome (FCS), severe hypertriglyceridemia (SHTG), and mixed hyperlipidemia. Plozasiran has demonstrated a favorable safety profile to date with treatment emergent adverse events reported that reflect the comorbidities and underlying conditions of the study populations. Plozasiran is currently being investigated in the PALISADE Phase 3 clinical study in patients with FCS, which recently completed, and the Phase 3 SHASTA-3 and SHASTA-4 studies in patients with SHTG.
Plozasiran has been granted Orphan Drug Designation and Fast Track Designation by the
About Plozasiran EAP
Arrowhead is committed to bringing new investigational medicines to patients with serious diseases as quickly and efficiently as possible. The company has established an early access program (EAP) for some individuals living with FCS. As with any investigational medicine that has not been approved by regulatory authorities, investigational plozasiran may or may not be effective in treating your diagnosis or condition, and there may be risks associated with its use. If you are a patient or caregiver wishing to know more about this plozasiran EAP for FCS, please discuss this EAP and all treatment options with your treating physician. If you are a treating physician and are seeking information about the plozasiran EAP or would like to request access for a patient, please contact EAP@arrowheadpharma.com.
About Arrowhead Pharmaceuticals
Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing.
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Source: Arrowhead Pharmaceuticals, Inc.
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Arrowhead Pharmaceuticals, Inc.
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ir@arrowheadpharma.com
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Source: Arrowhead Pharmaceuticals, Inc.
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