Pfizer's 'entrenched' tafamidis franchise will be tough to challenge for Alnylam, BridgeBio: analysts

With backing from an FDA advisory committee and results from a positive phase 3 trial, respectively, Alnylam and BridgeBio are each on track to enter the blockbuster transthyretin amyloidosis cardiomyopathy (ATTR-CM) market. But doctors say they’ll mostly stick with Pfizer’s first-to-market franchise, according to two analyst groups.

Pfizer’s tafamidis, sold as Vyndaqel and Vyndamax, will largely be able to maintain a 60%-plus share of treated patients in the next few years as the overall ATTR-CM market grows, Leerink Partners analysts said in a Monday note based on a survey of 57 doctors who treat the condition.

Separately, after talking to a cardiology opinion leader, analysts at Evercore ISI concluded that tafamidis “seems quite entrenched” and “might be difficult to displace,” according to a Friday note.

Tafamidis will likely remain the ATTR-CM leader even as Alnylam’s Onpattro and BridgeBio’s acoramidis hit the scene, according to the analysts.

For Onpattro, external advisers to the FDA last week voted 9-3 in support of the RNA silencer’s use in ATTR-CM. But because Onapttro only showed a “small” benefit in a phase 3 trial, several advisory committee members frowned upon the idea of using the Alnylam drug as an alternative to tafamidis in newly diagnosed patients.  

Similarly, 68% of doctors polled by Leerink said they would use Onpattro—if approved—only after a patient fails on tafamidis. In their responses, several doctors said tafamidis, as an oral med, is more convenient than Onpattro, which is an infusion. Some said tafamidis is well established and that there’s no need to use another drug.

In addition, the expert interviewed by Evercore ISI said he would also reserve Onpattro for patients who’ve failed on tafamidis. 

Pfizer’s tafamidis stabilizes TTR to prevent progression of ATTR. Theoretically, it could work alongside the RNA-interfering Onpattro because of the drugs’ different mechanisms of action. Opinions on this combination approach are divided, with 54% of doctors surveyed by Leerink saying they are unsure about its validity. Evercore’s expert said doctors likely won’t use the two drugs together unless data prove the benefit.

Meanwhile, market penetration might be easier for another TTR stabilizer in BridgeBio’s acoramidis. In a phase 3 trial, acoramidis reduced the risk of cardiovascular-related death by 30% and CV-related hospitalization by 50% compared with placebo in ATTR-CM. Alnylam’s Onpattro doesn’t have statistically powered CV outcomes data.

More than 80% of physicians surveyed by Leerink see acoramidis as an attractive option for ATTR-CM. About half of the doctors are willing to use acoramidis as a first-line therapy, but most still expect a minimal shift from tafamidis.

Evercore’s expert argued the two stabilizers are too similar to support switching and that acoramidis’s twice-daily dosing is a disadvantage compared with tafamidis’s once-daily frequency. But because reimbursement hurdles and out-of-pocket costs are a problem for patients on tafamidis, BridgeBio could convince doctors to switch with “a significant cost advantage,” he said.

Based on the survey, Leerink’s analysts picture a different outlook for tafamidis than the Wall Street average. Rather than a fast revenue increase in the next few years followed by a decline beginning around 2025, the Leerink team expects tafamidis to continue to grow from $2.4 billion in 2022 and peak at nearly $4 billion around 2029.

As for acoramidis, the Leerink team believes the drug could reach $1.8 billion in sales in 2030. Current consensus has Onpattro’s 2030 sales at $654 million, according to Leerink.

Alnylam is gunning for another ATTR-CM nod for its second-generation silencer, Amvuttra, with a phase 3 readout expected soon. The Leerink team expects Amvuttra will hold the largest share within the silencer class, pegging its potential at $3.4 billion by 2030 versus a consensus estimate of $5 billion.