Mizuho Medy Co., Ltd.

iStock, Jolygon Alnylam and BridgeBio are competing for people who are switching from Pfizer’s blockbuster ATTR amyloidosis drug tafamidis while all three companies are fighting for new patients. A three-way tussle has emerged in the growing ATTR amyloidosis market as Alnylam and BridgeBio Pharma have secured FDA approvals to challenge Pfizer. Tafamidis, which Pfizer sells as Vyndaqel, Vyndamax and Vynmac, had the ATTR amyloidosis with cardiomyopathy (ATTR-CM) market to itself for five years. But BridgeBio won approval for Attruby, a drug with the same mechanism of action as tafamidis, in November 2024. Then the oral transthyretin stabilizers were joined on the market by the first silencer, Alnylam’s Amvuttra, in March. Amvuttra was already approved in ATTR with polyneuropathy (ATTR-PN). ATTR-CM causes stiffening of cardiac muscle and heart failure, leading to death in around 2.5 years if left untreated. Cardiac capacity cannot be regained once lost. BridgeBio estimates there are around 240,000 ATTR-CM patients in the U.S. and BMO Capital Markets analyst Kostas Biliouris said he believes the market is big enough to accommodate multiple assets. Even so, competition is inevitable and the stakes are high. Pfizer Bullish as Rivals Arrive Pfizer reported $5.4 billion in sales for tafamidis in 2024, up more than 60% year on year. Matt Outten, chief commercial officer at BridgeBio, said at a Leerink investor event in March that around 24,000 people are on tafamidis. And about 30% to 40% of patients on tafamidis “are probably progressing” while a further 2,000 to 3,000 people are being newly diagnosed each quarter, he added. Alnylam and BridgeBio are now competing for people who are switching from tafamidis. Pfizer CFO David Denton acknowledged the effect of the new entrants on a call with analysts to discuss 2025 guidance, saying that “Vyndaqel’s growth will be tempered primarily due to the unfavorable impact of the IRA and new competition in the U.S.” Pfizer CEO Albert Bourla provided a detailed look at how the company expects the market to evolve at a TD Cowen event in March. The chief executive is confident Pfizer can keep current users, arguing that physicians “will never switch a patient to something different” when a medicine is working well. He is equally bullish on the company’s ability to compete for first-line users. Bourla said that Pfizer “will maintain a lion’s market share” for new prescriptions “because of the network, the understanding of physicians of the brand.” Asked if he expects Pfizer to dominate new prescriptions, Bourla said “correct,” adding that the company will be “super dominant on the current prescriptions.” Alnylam Targets First-Line Market Alnylam has other ideas. On a conference call with analysts to discuss the FDA approval, Alnylam CEO Yvonne Greenstreet said Amvuttra has the potential to become the new standard of care. Tolga Tanguler, chief commercial officer at the company, used the call to make the case that ATTR-CM patients, knowing cardiac function cannot be regained, will want to get the injectable Amvuttra as a first-line therapy. The biotech is forecasting sales of Amvuttra and Onpattro, the company’s other approved ATTR-PN drug, will rise to between $1.6 billion and $1.725 billion this year, a 36% increase at the midpoint of the range. Last year, when Alnylam only had approvals in ATTR-PN, the franchise grew 34%. Alnylam is charging a premium for Amvuttra. The annual wholesale acquisition cost for Pfizer’s tafamidis is $268,000 . BridgeBio priced Attruby at $244,500 a year. Alnylam set Amvuttra’s list price at an annual cost of $476,000. Tanguler said Alnylam will cut the net price of Amvuttra “via rebates and value-based agreements” as prescription uptake increases. The Inflation Reduction Act could also impact what patients pay for Amvuttra. The law capped Medicare Part D out-of-pocket spending at $2,000. A patient who has already hit the cap, because they are on other medications, will pay nothing to take tafamidis or Attruby. Amvuttra is a Medicare Part B drug. These services have a 20% coinsurance. Medicare Advantage caps the annual cost at $9,350. Amvuttra has confirmed coverage for virtually all insured ATTR-PN patients, Tanguler said, and Alnylam expects similarly broad coverage in ATTR-CM. The biotech is talking to U.S. payers and expects ATTR-CM sales to start ramping up in the second half of 2025. Alnylam is taking other steps to ensure patients can access Amvuttra, with a focus on the 170 health systems where 80% of ATTR-CM patients are treated. Alnylam has been optimizing access pathways at those health systems to ensure people can receive the drug “at a convenient location, whether that’s an office, at an infusion center or, in some cases, in the patient’s home,” Tanguler said. The biotech had nearly 2,000 alternate sites of care as of March 20, Tanguler said, and was close to its goal of establishing treatment sites within 10 miles of 90% of patients. BridgeBio Builds Launch Momentum Alnylam is presenting Amvuttra’s quarterly subcutaneous dosing as a strength. BridgeBio pushed back against that idea. Outten said some ATTR-CM patients cannot drive or prefer not to. Family members might need to take hours out of their days to drive patients, who are often seniors, for injections, Outten said. While Alnylam’s roll out of alternate sites of care could bring down geographic barriers to Amvuttra use, Outten expects some patients to prefer oral treatments. ATTR-CM patients already take pills multiple times a day for conditions such as high blood pressure, Outten said, so adding another drug has little effect on their routines. Data on BridgeBio’s Attruby launch predate the approval of Amvuttra. The first two months of the launch exceeded expectations , BMO’s Biliouris said, with around 500 HCPs writing prescriptions for more than 1,000 patients. Biliouris predicted BridgeBio will generate first-quarter sales of $7 million to $14 million, beating the $5 million to $6 million consensus analyst forecast. The competitive landscape looks likely to change in the coming years. Pfizer’s tafamidis is set to lose patent protection in the U.S. in 2028, allowing cheaper generic copies to come to market. Tanguler said the availability of generics might make combination therapy viable. In an April 4 note to investors, Mizuho analysts said that Pfizer’s work on a tafamidis tablet, which is in Phase I , could result in a formulation with patent protection through 2043. The Mizuho team cited Pfizer’s investment in the tablet formulation as evidence the ATTR-CM market “is likely to be more durable beyond 2028.” With Alnylam, BridgeBio and Pfizer all betting on the opportunity, and generic companies waiting in the wings, the stage is set for intense competition and blockbuster sales.

BridgeBio revealed Thursday that prescriptions for its recently approved rare heart disease drug Attruby substantially beat analyst projections — an update that is likely to further boost confidence in the company’s commercialization efforts. According to its fourth-quarter earnings report, there had been 1,028 Attruby prescriptions as of Feb. 17, up from 430 last month, when the company presented figures at the JP Morgan Healthcare Conference on Jan. 13. Those JPM numbers had already represented a strong start roughly seven weeks into the drug’s launch. The company did not report exact sales figures for the 1,028 prescriptions, but noted in a press release that it recorded $2.9 million in Q4 Attruby sales. The drug was approved Nov. 22 to treat transthyretin amyloid cardiomyopathy (ATTR-CM). BridgeBio’s stock $BBIO was up more than 6% in Thursday’s pre-market session. Ahead of Thursday’s report, several analysts attempted to forecast how prescription numbers would look, with a consensus falling in the 700s and 800s. The JPM numbers had many analysts already predicting Attruby will beat the Wall Street consensus’ sales forecasts this year, which is roughly $80 million to $100 million. TD Cowen’s Tyler Van Buren conducted an investor poll asking how many prescriptions would be needed for Attruby’s strong momentum to continue. The weighted average from respondents was 776 prescriptions. However, 45% of those who responded said Attruby would need at least 900 prescriptions. Van Buren described a 900-prescription figure as “an unreasonable expectation,” as growth continuing at that rate would lead to $153 million in 2025 sales — a figure he said was 80% higher than the Wall Street consensus. Mizuho analyst Salim Syed said that assuming the same growth from JPM, there would be 867 prescriptions in Q1 of 2025. And although Leerink analyst Mani Foroohar didn’t give a prescription forecast, he wrote last month that his estimate of $115 million in full-year sales is likely to be conservative. Despite the strong launch, questions will remain for BridgeBio throughout the year. The FDA is expected to decide by March 23 on an Alnylam drug that will compete with Attruby in the same indication. The two companies have heavily debated about why each of their medicines is best for patients. BridgeBio could also face questions about how many of its prescriptions are coming from treatment-naïve patients versus patients who have previously received Vyndaqel, a Pfizer drug already approved in the space. BridgeBio did not break down prescription numbers by patient type, but a spokesperson told Endpoints News the company saw “broad adoption across all patient types and HCP settings.” Attruby was also approved last week in the EU, where it will be branded as Beyonttra. The company’s cash and cash equivalents sit at $681.1 million as of Dec. 31. Editor’s note: This article was updated with information about BridgeBio’s stock movement.

Japan-based Kyowa Kirin fronted $330 million last year and pledged up to $1.1 billion in milestones to split the U.S. profits of ziftomenib\n Kura Oncology and Kyowa Kirin claim to have scored a phase 2 win for their oral leukemia treatment while reassuring analysts about the lack of any hard data to prove it.Ziftomenib, an oral selective menin inhibitor, was undergoing a trial in patients with relapsed or refractory NPM1-mutant acute myeloid leukemia. The study hit its primary endpoint of demonstrating a statistically significant improvement in complete response (CR) rate as well as partial hematological recovery (CRh).Kura and Kyowa used the announcement to confirm that they are on track to file a new drug approval application with the FDA in the second quarter of 2025. However, the release didn’t include any data, with the companies only promising to submit their topline findings at “an upcoming medical meeting” in the second quarter.Analysts at Mizuho said that Kura had pointed to other biotechs who had been similarly coy with their cancer data to justify their decision to withhold more information. The reason for the lack of transparency was “largely due to conference rules,” according to the analysts’ note.“[The trial] was powered to detect a CR/CRh rate of 20-30% and the company noted safety and tolerability in-line with previous data, all of which reads fine to us (i.e. likely in the \"approvable\" range),” the analysts said. The second half of this year will see Kyowa and Kura launch two phase 3 trials for ziftomenib. One of these will see the drug combined with chemotherapy in AML patients with mutations in the NPM1 or KMT2A genes. The other will test ziftomenib along with Venclexta and Vidaza in NPM1 patients who are unfit to receive intensive chemotherapy.“Even with approved therapies, up to 70% of patients who achieve a first CR will see their AML return within three years,” Kura’s Chief Medical Officer Mollie Leoni, M.D., said in the Feb. 5 release.“Given this urgent need, we are pleased with the outcome of these FDA interactions and look forward to initiating our phase 3 trials to establish the benefit-risk profile of ziftomenib in both the intensive and non-intensive chemotherapy settings,” Leoni added.Japan-based Kyowa Kirin fronted $330 million last year and pledged up to $1.1 billion in milestones to get in on the ziftomenib action. The two companies are sharing responsibility for launching various trials in AML and other blood cancers “over the next several years,” with Kura funding the development of ex-U.S. trials until the end of 2028, after which point the biotechs will split the costs.Kura began 2024 posting fresh phase 1b data suggesting ziftomenib performed best on top of a standard-of-care combo regimen in newly diagnosed patients with specific mutations.