Positive results from a phase 3 trial of Alnylam’s Onpattro—which the company revealed last week—will likely set it up for a key label expansion to treat the heart failure condition transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM), analysts say.
But there is some doubt about the drug's ability to be a serious challenger to Pfizer’s market leading Vyndaqel/Vyndamax (tafamidis) franchise.
For Alnylam, the best news from the trial was that Onpattro staved off the rapid decline in functionality that accompanies ATTR. In a six-minute walk test, those on the infused drug covered 8.1 fewer meters after 12 months compared with a 21.3-meter decline for those on placebo. The estimated median difference between treatment and placebo was 14.7 meters.
The bad news had to do with the secondary endpoints—all-cause mortality and the frequency of all-cause hospitalizations and urgent heart failure visits—which failed to reach statistical significance.
“The likelihood for Onpattro (patisiran) to be approved in ATTR cardiomyopathy has increased, but commercial use remains to be seen,” Berenberg Capital Markets analyst Zhiqiang Shu, Ph.D., wrote to clients. “The data confirm that the knockdown mechanism works, but there was no reversal of disease progression or any indication that patisiran was better than the standard of care. Such a lack of differentiation clouds our view on potential uptake.”
While Alnylam touted results of its six-minute walk test, they fell short of the 37-meter average Pfizer's tafamidis has achieved, though Evercore ISI warned about the comparison considering tafamidis was tested on a population with milder disease. The Evercore analysts also pointed out that the drugs' different mechanisms of action could affect how quickly they work.
Key opinion leaders interviewed by Berenberg and Evercore had varying views of the data. While Berenberg’s expert said he would not prescribe Onpattro to the majority of his patients, Evercore’s expert was much more open to using it, especially for those at the sicker end of the disease spectrum.
Kevin Alexander, M.D., professor and cardiologist at Stanford University, said he would likely prescribe Onpattro to those on Vyndaqel/Vyndamax, with the assumption that the drugs could have a synergistic effect.
The data were a bit of a surprise considering the stunning results nine months ago of BridgeBio’s ATTR-CM candidate acoramidis, which came up short of placebo in the six-minute walk test.
For a variety of reasons, analysts at Mizuho Securities believe that the differing results bode well for the prospects of acoramidis.
“There are a lot of issues with this dataset,” wrote Mizuho analyst Salim Syed in a note to investors. “And the read-across to BridgeBio's acoramidis is actually positive.”
After seeing results from multiple studies, Mizuho's Syed said that the six-minute walk test is “becoming less reliable” and that mortality should be the key measurement tool in the disease.