- Pfizer Inc. last week reported its experimental drug candidate tafamidis succeeded in a Phase 3 study of patients with a rare disease known as transthyretin (TTR) cardiomyopathy, sending shares of potential competitors sliding in what one analyst called a "very rare late-stage pipeline surprise."
- According to topline results, treatment with tafamidis reduced all-cause mortality and cardiovascular-related hospitalizations versus placebo at 30 months in patients with the generally fatal heart condition.
- Full data from the study isn't yet available, but Pfizer said it plans to discuss the results with regulators to determine a potential path toward approval. The drug's unexpected success could represent a competitive threat to Alnylam Pharmaceuticals Inc. and Ionis Pharmaceuticals Inc., both of which are awaiting U.S. approval of drugs for a broader disease spectrum caused by the same misfolding of TTR protein.
Over the course of the past several years, Alnylam and Ionis have pushed their respective treatments for hereditary TTR amyloidoisis (ATTR) through late-stage clinical testing to regulatory review by the Food and Drug Administration.
Alynlam's drug, called patisiran, is seen by many analysts as more potent and efficacious in easing the symptoms of the rare disease — which causes progressively more severe organ damage, leading to neuropathy and cardiomyopathy.
Ionis may win FDA approval for its rival candidate inotersen first, with a decision expected in early July. Alnylam won't be far behind and could potentially win an OK by August.
But Pfizer's results could complicate the competitive mix.
The pharma enrolled 441 patients into the Phase 3 study, which tested tafamidis' effect on mortality and hospitalization in patients with TTR cardiomyopathy. A previous trial of the drug in patients with TTR familial amyloid polyneuropathy (FAP) failed to hit its objectives, leading the FDA to reject the drug in 2012.
Pfizer did have success in Europe, winning approval of tafamidis for TTR-FAP in 2011.
Expectations for tafamidis, therefore, weren't high and the announcement from Pfizer appeared to take investors by surprise.
"Even for [a] company the size of Pfizer, this program may be at least ~4% accretive to [earnings per share]," said Evercore ISI analyst Umer Raffat.
Shares in Alnylam fell 8.3% last Thursday, when the results were disclosed, and plunged a further 15% Monday morning. Ionis was less affected but shares in the biotech still slid nearly 10% from closing price on March 29.
Several key questions remain unanswered, though. Pfizer tested two doses in the Phase 3 study and pooled the results from both arms to compare versus placebo. Without more detailed data, it's unclear which led to greater benefit.
The study also combined all-cause mortality and heart-related hospitalization frequency into a single primary endpoint, making it difficult to tell the degree of mortality benefit from tafamidis treatment.
Even so, tafamidis looks to be a new rival to Alnylam's patisiran and Ionis' inotersen — at least in the narrower pool of patients who exhibit cardiomyopathy.
Alnylam hopes patisiran will receive a label from the FDA that includes patients with both neuropathy and cardiomyopathy, but trial results are limited only to individuals with herditary forms of the disease. Pfizer, on the other hand, tested tafamidis in patients with both hereditary and wild-type TTR cardiomyopathy.
If both drugs are approved, doctors could face a choice between a "potentially more potent, injectable drug" in Alnylam's patisiran versus an oral treatment with a "clear cardiovascular outcomes benefit" in Pfizer's tafamidis, wrote fellow Evercore ISI analyst Steve Breazzano in a March 29 note.