Bridgebio sets its heart on besting Pfizer
With phase 3 data approaching, it should soon become clear whether Bridgebio’s amyloidosis project really has an edge over Pfizer’s Vyndaqel.
Bridgebio has long claimed that its amyloidosis contender, acoramidis, is more potent than Pfizer’s similarly acting blockbuster Vyndaqel. These claims will soon be put to the test, with the first data from the phase 3 Attribute-CM study of acoramidis due by the end of the year.
The readout, from part A of the study, will include 12-month results on the six-minute walk test, the primary endpoint, and Kansas City cardiomyopathy questionnaire scores. On the former, Bridgebio believes that, in order to differentiate acoramidis from Vyndaqel, it will need to show a decline from baseline of 20 metres or less.
|% of market cap||58%|
|Event type||Data from part A of phase 3 ATTRibute-CM trial|
|Indication||Transthyretin amyloid cardiomyopathy|
Attribute-CM is evaluating acoramidis in wild-type and hereditary transthyretin amyloid (ATTR) cardiomyopathy, the same indication for which Vyndaqel was approved in 2019 on the basis of the Attr-act trial.
Both acoramidis and Vyndaqel are oral small molecules designed to stabilise transthyretin, the protein that in amyloidosis is broken down into insoluble amyloid fibrils, which build up in the patient’s organs. Acoramidis produces “near-complete” stabilisation, while Vyndaqel is a partial stabiliser, which is why Bridgebio believes that its molecule could be best in class.
It therefore might seem strange that the group is setting its sights on a decline in the six-minute walk test. However, this would represent an improvement over the 25m drop seen with Vyndaqel at 12 months in Attr-act.
To put this into context, the placebo group in Attr-act had a 56m decline in 6MWT at the same time point. Bridgebio expects a similar performance from the placebo arm in Attribute-CM – specifically, a 45-60m reduction in 6MWT – Leerink analysts noted.
If part A of the pivotal trial is positive, Bridgebio plans to file for FDA approval in mid-2022, and will use a priority review voucher, gained via the approval of Nulibry, to speed things up.
A spokesperson for Bridgebio, which acquired acoramidis when it bought back Eidos last year, told Evaluate Vantage that this would be a request for full, rather than accelerated approval. Still, Attribute-CM also has a part B, which will yield 30-month all-cause mortality data in 2023. These could be used to expand acoramidis’s label, assuming all goes smoothly.
The part B results will also give investors another chance to stack acoramidis up against Vyndaqel. Attr-act found a 30% reduction in the risk of death with the Pfizer drug versus placebo over 30 months (ESC 2018 – Pfizer impresses with tafamidis, but amyloidosis battle goes on, August 27, 2018).
Bridgebio is also evaluating acoramidis in hereditary ATTR polyneuropathy, in the phase 3 Attribute-PN study. This market is currently owned by Alnylam, with that group’s intravenous RNAi therapy, Onpattro, already approved here, and its subcutaneous follow-up, vutrisiran, due an FDA approval decision by next April.
Vyndaqel is available in Europe for polyneuropathy at a 20mg dose, but was knocked back in this indication by the FDA on lacklustre data.
Alnylam is also hoping to move into the cardiomyopathy segment, with results from the pivotal Apollo-B study of Onpattro due in mid-2022, also primarily evaluating 6MWT. For Bridgebio to compete with both of its bigger rivals, Attribute-CM will need to impress.