Transthyretin Amyloid Cardiomyopathy

A US drug pricing watchdog has raised the range by which it thinks Pfizer’s heart muscle disease drug tafamidis, marketed as Vyndamax and Vyndaqel, should be priced annually, but it’s still recommending an 85% to 95% cut, according to a final analysis released this week. The Institute for Clinical and Economic Review (ICER) wrote that the price benchmark for tafamidis, a transthyretin stabilizing agent, should range between $13,600 to $39,000 annually. This final recommendation comes with a higher price than ICER previously released in July , when the organization set the limits between $8,500 and $36,000 per year. Pfizer’s current annual list price is almost $200,000. In a statement to Endpoints News , a Pfizer representative wrote that “the use of QALY as a [clinical effectiveness] measure is well established, however, in rare diseases, this poses some challenges and bias particularly against elderly populations suffering from serious diseases who have a shorter life expectancy and less time to benefit from treatment.” The drug first won approval in 2019, making it the first in the class of drugs to be approved for transthyretin amyloid cardiomyopathy (ATTR-CM), although other competitors are making their way through the development process, like BridgeBio’s acoramidis , which has a PDUFA date set for late November, and Alnylam’s RNA silencing agent Amvuttra (vutrisiran), which was just submitted for an sNDA to the FDA this month. The final price range for Pfizer covers tafamidis and acoramidis, but not Amvuttra “because of the timing of new information on vutrisiran and lack of data needed for modeling,” ICER said.

In its final analysis of Pfizer Inc. 's widely used drug for transthyroid amyloid cardiomyopathy (ATRCM), the U.S. drug cost regulator called for a reduction of at least 85 percent from its current list price of nearly $268,000 a year to meet generally accepted cost-effectiveness standards. The conclusion, made official in the latest ATRCM report released Monday by the Institute for Clinical and Economic Review (ICER), makes clear that Pfizer's two tafetamines, Vyndaqel and Vyndamax, are subject to the discount requirement. According to ICER's data analysis, in order to meet the cost-effectiveness criteria of between $100,000 and $150,000 per quality-adjusted life year (QALY) or equivalent life year acquired, the annual cost of Tarfamides and the thyrotropin stabilizer category to which it belongs should be adjusted to between $13,600 and $39,000. That means a price cut of between 85 and 95 per cent. The proposed annual cost range is revised up from a preliminary draft report in July. In its response, Pfizer reiterated the challenges and biases it faces in using QALEs as a cost-effectiveness measure for rare diseases, particularly for older patients who have a shorter life expectancy and limited time to benefit from treatment. In addition, the report comes at a time when the FDA is about to make a decision on BridgeBio Pharmaceuticals' competing drug acoramidis, and Alnylam Pharmaceuticals recently submitted an application for its RNA silencer Amvuttra (vutrisiran). This could further affect the competitive landscape of the ATRCM market. It is worth noting that ICER's price assessment covered Tafamidi and acoramidis, but did not include Amvuttra. Although Amvuttra was approved by the FDA for the treatment of ATR polyneuropathy in 2022 and has an annual price tag of $463,500, ICER said there is still not enough data to build an economic model for it. ICER's chief medical officer, Dr. David Rind, noted that the reasons for the price range adjustment include a change in the mortality estimate methodology and the correction of a calculation error in the previous quality of life assessment. At the same time, he highlighted the difficulty in economic evaluation of Amvuttra, especially the lack of data on the prediction of disease change in patients with NYHA Class III heart failure. However, he expects that the information may eventually be made public to meet the requirements of the European health assessment. In the final report, ICER also raised the complexity of comparing the net health benefits of Amvuttra versus stabilizers, noting that the question of the advantages of combination therapy versus monotherapy needs further study. To that end, the group recommends that researchers work to build a comparative profile of the three drugs and stresses the importance of randomized clinical trials to answer this question.

- Recommendation based on NEURO-TTRansform Phase 3 results showing WAINZUA demonstrated consistent and sustained benefit improving neuropathy impairment and quality of life versus placebo CARLSBAD, Calif., Oct. 21, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced today that Ionis' and AstraZeneca's WAINZUA (eplontersen) has been recommended for approval by the Committee for Medicinal Products for Human Use (CHMP) in the European Union (EU) for the treatment of hereditary transthyretin-mediated amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy, commonly referred to as hATTR-PN or ATTRv-PN. If approved by the European Commission, WAINZUA will be the only approved medicine in the EU for the treatment of ATTRv-PN that can be self-administered monthly via an auto-injector. The CHMP based its opinion on the positive NEURO-TTRansform Phase 3 trial which showed that through 66 weeks, patients treated with WAINZUA demonstrated consistent and sustained benefit on the co-primary endpoints of serum transthyretin (TTR) concentration and neuropathy impairment measured by modified Neuropathy Impairment Score +7 (mNIS+7), and key secondary endpoint of quality of life (QoL) on the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) versus external placebo. WAINZUA continued to demonstrate a favorable safety and tolerability profile throughout the NEURO-TTRansform trial. ATTRv-PN is a debilitating disease that leads to peripheral nerve damage with motor disability within five years of diagnosis and, without treatment, is generally fatal within a decade. WAINZUA is a once-monthly RNA-targeted medicine designed to reduce the production of TTR protein at its source. "Hereditary transthyretin-mediated amyloidosis with polyneuropathy remains a progressive and debilitating disease in Europe and other parts of the world, despite currently available medicines," said Brett P. Monia, Ph.D., chief executive officer, Ionis. "The CHMP recommendation is an important step toward making WAINZUA available in Europe, which, if approved, will be the only medicine in the EU for the treatment of transthyretin-mediated amyloidosis with polyneuropathy that can be self-administered monthly via an auto-injector. We are proud to partner with AstraZeneca whose global leadership and expertise positions our alliance to rapidly and effectively bring WAINZUA to many people living with hereditary transthyretin-mediated amyloidosis with polyneuropathy in Europe, pending the EMA's decision." In December 2023, eplontersen was approved in the U.S. for the treatment of ATTRv-PN, under the brand name WAINUA™ (eplontersen). WAINUA is now gaining approvals in additional countries worldwide, including Canada. As part of a global development and commercialization agreement, AstraZeneca and Ionis are commercializing WAINUA in the U.S. The companies are seeking regulatory approval in Europe and other parts of the world where AstraZeneca has exclusive rest of world commercialization and development rights. Eplontersen has also been granted Orphan Drug Designation in the U.S. and in the EU for the treatment of transthyretin-mediated amyloidosis (ATTR). Eplontersen is also currently being evaluated in the global CARDIO-TTRansform Phase 3 study for the treatment of adults with ATTR-CM. The trial is fully enrolled with more than 1,400 patients – making it the largest, most comprehensive study to date in this patient population. More information on the CARDIO-TTRansform study (NCT04136171) is available at . About TTR Amyloidosis ATTR is caused by the accumulation of liver-derived misfolded TTR protein in tissues, such as the heart and the peripheral nerves, causing organ damage and failure. ATTR then causes complications, leading to cardiovascular, neurological and renal diseases such as heart failure and chronic kidney disease. There are both hereditary (ATTRv) and non-hereditary (wild-type) forms of ATTR. ATTR is a rapidly progressive and fatal disease that requires timely recognition of symptoms. ATTR has several phenotypes including ATTR-cardiomyopathy (CM), which predominantly impacts the heart, potentially leading to heart failure, ATTR-polyneuropathy (PN), which predominantly affects the peripheral nervous system and mixed phenotype, where patients experience symptoms of both. Worldwide, there are an estimated 300,000 – 500,000 patients with ATTR-CM and about 10,000 – 40,000 patients with ATTRv-PN. About NEURO-TTRansform NEURO-TTRansform is a global, open-label, randomized trial evaluating the efficacy and safety of eplontersen in patients with ATTRv-PN at week 35, week 66 and week 85. The final analysis comparing eplontersen to an external placebo group was completed at week 66. All patients were then followed on treatment until week 85 and evaluated four weeks after the last dose in an end-of-trial assessment. Following treatment and the end-of-trial assessments, patients were eligible to enter an open-label extension study to continue receiving eplontersen once every four weeks or enter a 20-week post-treatment evaluation period, which is still ongoing. Full results from the NEURO-TTRansform trial were published in The Journal of the American Medical Association (JAMA) demonstrating the benefit of eplontersen across the spectrum of ATTRv-PN at 35, 66 and 85 weeks of treatment. About WAINZUA / WAINUA™ (eplontersen) Eplontersen is a once-monthly RNA-targeted medicine that provides upstream suppression of transthyretin (TTR) production and is designed to precisely target and reduce the production of TTR protein at its source in the liver. WAINZUA has been approved in the U.S. and Canada under the brand name WAINUA™ (eplontersen) for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults, commonly referred to as hATTR-PN or ATTRv-PN. Please see link for full U.S. Prescribing Information. WAINZUA is not yet approved for any indication in Europe. U.S. INDICATION for WAINUA™ (eplontersen) WAINUA injection for subcutaneous use 45 mg is indicated for treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. IMPORTANT SAFETY INFORMATION for WAINUA™ (eplontersen) WARNINGS AND PRECAUTIONS Reduced Serum Vitamin A Levels and Recommended Supplementation WAINUA leads to a decrease in serum vitamin A levels. Supplement with recommended daily allowance of vitamin A. Refer patient to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency occur. ADVERSE REACTIONS Most common adverse reactions (≥9% in WAINUA-treated patients) were vitamin A decreased (15%) and vomiting (9%). Please see link to U.S. Full Prescribing Information for WAINUA. About Ionis Pharmaceuticals, Inc. For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionis.com and follow us on X (Twitter) and LinkedIn. Ionis Forward-looking Statements This press release includes forward-looking statements regarding eplontersen, Ionis' business, and the therapeutic and commercial potential of Ionis' commercial medicines, additional medicines in development and technologies. Any statement describing Ionis' goals, expectations, financial or other projections, intentions, or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended Dec. 31, 2023, and most recent Form 10-Q, which are on file with the SEC. Copies of these and other documents are available at . Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc. WAINUA™ is a trademark of AstraZeneca plc. Ionis Investor Contact: D. Wade Walke, Ph.DD. [email protected] 760-603-2331 Ionis Media Contact: Daria Binder [email protected] 760-603-4679 SOURCE Ionis Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED