Pfizer has scored the kind of potentially game-changing pivotal data for tafamidis in rare cases of transthyretin amyloid cardiomyopathy that analysts have been on the lookout for. And the pharma giant is rolling out an expanded access program for ATTR-CM patients now — just as a rival therapy from Alnylam is hitting the market for the first time.
Researchers today followed up positive top-line data with the news that tafamidis spurred a 30% drop in mortality risk along with a 32% reduction in the risk of cardio-related hospitalization. That’s good enough to win over a key crowd of top analysts, but you can bet that there will be plenty of questions today as everyone hunts for the devil in the detail. And Alnylam wasted no time in raising doubts about the data, which is likely going to relieve investors fretting over the competition.
Credit Suisse analysts earlier noted that “even a modest improvement in mortality (10% to 15%) would be favorable.” Anything 20% to 25% could prove to be a game-changer, they added, in a field where a landmark RNAi therapy from Alnylam is about to hit the market and another — less attractive — therapy from Akcea and Ionis is likely right behind it.
The data also hit a secondary on an improvement in the reduction of performance in the 6-minute walk test along with an improvement in quality of life scores.
But some questions remain. And at first blush Alnylam got a quick thumbs up for remaining competitive as a market showdown looms between the leaders in the field.
Alnylam followed up by pointing out that Pfizer looks weakest where it looks strongest, without a statistically significant readout for hereditary ATTR. The company also spotlighted the pooled dose results, an unusual decision by Pfizer. They added:
- In APOLLO, over 50% of patisiran patients showed IMPROVEMENT relative to baseline on both mNIS+7 and Norfolk.
- In APOLLO cardiac subpopulation of hATTR patients*, patisiran resulted in:
- Decrease from baseline (i.e., IMPROVEMENT) in NT-proBNP levels (55% reduction for pati relative to pbo)
- 31.6% of pati patients had decrease change from baseline of NT-proBNP ≥30% and ≥300 pg/mL, a key mortality prognosticator, at Month 18, whereas no pbo patients had decreases of this magnitude.
Perhaps most significantly, Alnylam also believes that this field is primarily a growth opportunity, as new and better diagnoses identify a growing group of patients for both. In that scenario, patients and physicians can make their own choices as all the biotechs benefit.
You can get more details in the study published in the New England Journal of Medicine.
Investors seem fairly happy initially with both sides. Alnyam shares jumped 16% by the end of the day — a relief rally — while Pfizer stock ended down a couple of points.
Researchers offered pooled data for two doses of the drug — an 80 mg and 20 mg regimen — rather than breaking the results out into dosage groups, leaving it unlikely that they saw a clear dose response. Analysts will be following up Pfizer’s statement today with more questions on how the therapy worked. But it’s clear that Pfizer will be claiming an advantage here, providing one reason for CEO Ian Read’s recent vote of confidence that the company’s late-stage pipeline can provide the big drugs it needs to keep revenue on the upswing.
The drug is already armed with both a breakthrough therapy designation as well as a Sakigake title from Japanese regulators. Look for some quick marketing applications and an aggressive rollout if the data hold up.
What we also didn’t get immediately was much detail on safety data. The drug arm and placebo had a “comparable” safety profile, the company reported.
Credit Suisse has estimated peak sales at $600 million, with a shot at more under certain circumstances. The big question now is how much Alnylam — whose drug Onpattro was approved for TTR polyneuropthay — might be affected by the competition. According to the analysts:
Though the indications may be different, the products will likely compete, as physicians we spoke with indicated that many patients with cardiomyopathy tend to also have polyneuropathy and vice versa. A few physicians believe Alnylam’s product is the safer product and will use patisiran to treat cardiomyopathy while getting reimbursement for polyneuropathy. Other physicians expect to primarily prescribe tafamidis if the outcome data are clinically meaningful.
Pfizer, though, also faces a challenge in getting physicians to do a much better job at diagnosing TTR-cardiomyopathy. But their decision to begin a wide-open expanded access program is a clear shot over Alnylam’s bow. The drug is already approved as Vyndaqel and on the market to treat familial amyloid polyneuropathy.
Their market rivalry starts today.
Also affected by today’s announcement is Eidos Therapeutics $EIDX, which recently went public as it pursued its own work in the field.
“We believe the ATTR-ACT study findings bring us a significant step closer to our goal of providing an urgently needed therapy for a serious and often fatal disease,” said Brenda Cooperstone, Pfizer’s chief development officer for rare disease. “We look forward to continuing discussions with global regulatory authorities about the potential of tafamidis as a treatment option for people living with ATTR-CM.”
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