Tafamidis Meglumine

A BridgeBio Pharma drug developed for an increasingly prevalent cardiovascular condition has won FDA approval, marking a comeback for a company and a molecule with a turbulent history. But BridgeBio’s challenges aren’t over. The biotech’s new product must now compete against a blockbuster Pfizer medication already well established as the standard of care and fend off new competition on the way. The late Friday approval for the drug, acoramidis, covers the treatment of adults with cardiomyopathy caused by transthyretin-mediated amyloidosis, or ATTR. The disease stems from a genetic mutation though it can also develop as a consequence of aging. The FDA approval covers both types. BridgeBio’s twice-daily pill will be marketed under the brand name Attruby. In ATTR, abnormal versions of a liver protein called transthyretin lead to a buildup of amyloid protein in tissues and organs. When this buildup affects the heart, it can lead to cardiomyopathy, making it harder for the organ to pump blood. Attruby is a small molecule designed to bind to the abnormal TTR, stabilizing the protein and preventing it from leading to the amyloid buildup characterized by the disease. Pfizer’s ATTR cardiomyopathy drug, tafamidis, approved in 2019 and marketed as the four-times daily capsule Vyndaqel and the once-daily capsule Vyndamax, is also a TTR stabilizer. But Palo Alto, California-based BridgeBio set out to show its drug is the better stabilizer. That effort was almost derailed. Health IT Reducing Clinical and Staff Burnout with AI Automation As technology advances, AI-powered tools will increasingly reduce the administrative burdens on healthcare providers. By Dr. Michael Blackman, Chief Medical Officer at Greenway Health Nearly three years ago, BridgeBio reported preliminary data showing its drug failed to beat a placebo in the first part of a Phase 3 clinical trial, which assessed patients after 12 months. The company attributed the failure to a high placebo response. The disappointing results sank shares of the biotech by more than 70%. But the study’s design included a second part that would assess patients after 30 months of treatment. BridgeBio opted to continue the study, hoping longer treatment would lead to better outcomes. FDA approval of Attruby is based on the 30-month data from the Phase 3 study, which enrolled 632 patients with ATTR cardiomyopathy. Results showed the drug met the main goal of showing statistically significant improvement on a composite endpoint comprised of four measures of the disease. The results were published in the New England Journal of Medicine early this year. Speaking during a Friday evening webcast, BridgeBio CEO Neil Kumar drew distinctions between Attruby and Pfizer’s product. “This is the only oral stabilizer with the verbiage ‘near-complete stabilization’ in the label,” he said. “Almost all of benefits described downstream in the label stem from this near-complete stabilization. As early as three months, the earliest time point that we know of, this medicine begins to take action against a composite endpoint of cardiovascular hospitalization and death.” BridgeBio estimates 500,000 patients in the U.S. and European Union have ATTR cardiomyopathy, which represents a market opportunity of $15 billion to $20 billion. Right now, that market is dominated by Pfizer, which reported $3.9 billion in tafamidis sales in the first nine months of 2024, a more than 65% increase compared to the same period in 2023. But this market could soon be split among several products. Consumer / Employer Health Executives on Digital Transformation in Healthcare Hear executives from Quantum Health, Surescripts, EY, Clinical Architecture and Personify Health share their views on digital transformation in healthcare. By MedCity News Alnylam Pharmaceuticals develops drugs that silence genes, preventing them from causing disease-causing proteins. The biotech already markets Amvuttra for treating polyneuropathy caused by ATTR. But Alnylam has also tested Amvuttra, administered as a subcutaneous injection every three months, as a treatment for ATTR cardiomyopathy. On Monday, Alnylam announced the FDA accepted the company’s supplemental new drug application in this indication, setting a March 23, 2025 target date for a regulatory decision. Meanwhile, partners AstraZeneca and Ionis Pharmaceuticals market antisense oligonucleotide drug eplontersen, brand name Wainua, for treating polyneuropathy caused by ATTR. A Phase 3 trial is underway testing the drug in ATTR cardiomyopathy. In a note sent to investors, Leerink Partners analyst Mani Foroohar said Attruby’s label was the best-case scenario as the indication statement includes cardiovascular mortality and hospitalization, consistent with Pfizer’s product. Furthermore, Attruby can stake the claim of being the first and only product with a label specifying near-complete stabilization of TTR. That said, cracking Pfizer’s established market presence will be difficult. In results of a Leerink survey released in September, the Pfizer drug was physicians’ treatment of choice for cardiomyopathy caused by ATTR, given long their long experience with the product. There was an uptick in preference for gene silencing therapies, but mainly for treating polyneuropathy caused by the disease, the survey showed. Many physicians stated they would switch to another product only if a patient’s condition is not well controlled by the Pfizer drug. William Blair analyst Myles Minter said language in Attruby’s label stating the drug’s ability to reduce cardiovascular death is “a clear win for BridgeBio.” But Minter noted the absence on the label of any standalone all-cause mortality data, which is different than the Pfizer product’s label. Attruby did not lead to a statistically significant benefit on all-cause mortality compared to a placebo in its pivotal study. Minter said clinicians the firm spoke with at recent cardiovascular conferences continue to suggest the importance of not only the magnitude of cardiovascular event risk reduction, but also the timing of the onset of the drug’s effect given that cardiomyopathy can progress rapidly. He added that TTR-silencing drugs are best positioned for market differentiation. “We continue to view a reduction in all-cause mortality on label as a necessary distinction to gain major market share in ATTR-CM alongside Pfizer’s tafamidis,” Minter said. “Given the lack of all-cause mortality data included in the Attruby label, we believe Pfizer could start marketing more specifically around mortality benefit claims.” BridgeBio set Attruby’s wholesale price at $18,759.12 for a 28-day supply, which works out to about $244,500 annually. That’s a slight discount to Pfizer’s product, priced at $267,987 annually. But it’s still well above the $13,600 to $39,000 cost-effectiveness price range calculated by the Institute for Clinical and Economic Review, a non-profit organization that researches the value of drugs in order to determine what would be a fair price. Kumar said all patients who participated in Attruby’s Phase 3 study will continue to receive the drug for free for the rest of their lives. Attruby is still under review in Europe with a regulatory decision expected in 2025. Under a deal struck earlier this year, Bayer has exclusive rights to market the drug in Europe for ATTR cardiomyopathy. Bayer shelled out $310 million in upfront and near-term milestone payments; additional sales-based milestones were not disclosed. BridgeBio will also earn royalties from Bayer’s sales of the product. Image: Magicmine, Getty Images

The FDA on Friday approved BridgeBio Pharma's Attruby (acoramidis) to reduce cardiovascular death and cardiovascular-related hospitalisation in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), setting up a showdown with Pfizer's tafamidis, which has the same mechanism of action, but a more limited label. The clearance for Attruby, an oral TTR stabiliser, specifies that the drug provides near-complete stabilisation of TTR, which is not present in the tafamidis indication. The list price will be $18,759 for a 28-day supply.Tafamidis — marketed as Vyndamax and Vyndaqel — became the first drug approved by the FDA for ATTR-CM when it was greenlit in 2019. Since then, drugmakers have been racing to nab their own piece of the potentially lucrative heart disease pie. Last year, Pfizer's products brought in a total of $3.3 billion in global sales. Now, Attruby is set to reach patients faster than the other major horse in the race, Alnylam's RNAi therapeutic vutrisiran. A series of physician polls conducted by FirstWord this year has shown that, if approved, cardiologists view vutrisiran as an important new treatment option, but whether that therapy, or Attruby, can topple tafamidis and become the new standard of care will be dependent on different interpretations of available clinical data. For related analysis, see Physician Views Results: Cardiologists have much to ponder with ATTR-CM treatment options set to expand; Physician Views Poll Results: Amvuttra another compelling treatment option for ATTR-CM, say majority of cardiologists; and Physician Views Results: Cardiologist feedback suggests Alnylam well placed to take on Pfizer in ATTR-CM field.However, given Attruby's market lead on vutrisiran and the strength of its pivotal data, some Wall Street analysts have suggested that Alnylam could have a more challenging time commercialising its RNAi therapeutic — and that the TTR stabiliser poses more of a significant threat to Pfizer's stronghold.Mortality reduction, fastAttruby's approval was based on data from the ATTRibute-CM Phase III trial, which enrolled 632 patients with symptomatic ATTR-CM to receive either Attruby or placebo for 30 months.BridgeBio's drug met the study's primary goal by achieving statistically significant improvements over placebo on each of the four components of a composite endpoint: all-cause mortality (ACM), cardiovascular-related hospitalisations (CVH), NT-proBNP and 6-minute walk distance. Specifically, patients who received Attruby saw a 25% reduction in ACM and a 50% reduction in CVH at 30 months, with 81% of patients alive at that time point. And notably,  Attruby achieved a three-month time to separation of outcomes curve.By comparison, tafamidis demonstrated a 30% reduction in all cause mortality and 32% reduction in cardiovascular hospitalisations at 30 months in the ATTR-ACT study, with 70% of patients receiving Pfizer's therapy remaining alive at this cut-off. The drug had an 18-month time to separation on ACM and a nine-month time to separation on CVH.Global plansBridgeBio CEO Neil Kumar said the company plans to file for approval of Attruby in Japan and Brazil next. A submission in the EU — where Bayer holds exclusive commercialisation rights — is already under review, with a decision expected next year. Meanwhile, BridgeBio said it will receive a $500-million payment under a royalty funding agreement.