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Alnylam’s Onpattro back in the game against Ionis, thanks to NICE U-turn

England’s National Institute for Health and Care Excellence has decided to back Alnylam’s gene-silencing therapy Onpattro, following a thumbs-up to Ionis’ rival med Tegsedi. (Business Wire)

Ionis Pharmaceuticals and its RNAi drug Tegsedi got a head start with England’s National Health Service, putting the pressure on Alnylam’s rival med Onpattro. But now, the country’s cost-effectiveness gatekeeper has changed its mind and backed the Alnylam drug, too.

The National Institute for Health and Care Excellence (NICE) now recommends Onpattro to treat the ultra-rare disease hereditary transthyretin-mediated amyloidosis (hATTR) in adults with damage to peripheral nerves.

NICE’s drug evaluation experts still think Onpattro’s cost-effectiveness falls short of their usual threshold for a highly specialized drug. However, the committee reversed last year’s “no” vote after considering the benefits of halting—and potentially reversing—the condition, and the benefits that could offer patients for the rest of their lives.

They also weighed the “rarity and severity of the condition … and the innovative nature of the treatment,” the agency said in its recommendation.

Those benefits weren’t all that came into play, though. As companies usually do to win NICE backing, Alnylam offered a confidential discount off its list price of £7,676 ($9,560) per 10-mg vial.

There was never doubt about Onpattro’s clinical efficacy. In a 225-patient trial called Apollo, 56% of patients with hATTR amyloidosis polyneuropathy treated with Onpattro saw an improvement in symptoms after 18 months compared with 4% of patients on placebo.

In its previous rejection, NICE pointed to uncertainty about the drug’s long-term benefits. Alnylam is already working to prove that case by collecting data for up to five years, and it unveiled the latest numbers just a few days ago. Additional data from an ongoing open-label extension study showed patients on treatment for 30 months to 36 months were still benefiting from Onpattro.  

NICE wasn’t convinced, however; the committee noted that the study patients had been treated with Onpattro for different lengths of time, which could muddy the results. But the body did acknowledge Onpattro’s “future benefits could be greater than what was presented to the committee.”

 After NICE rejected both meds last year, Tegsedi won over the cost agency in April.

Onpattro is currently in a fierce race against Tegsedi in hATTR polyneuropathy in England and beyond, with both companies touting their drugs’ particular characteristics. While both are RNAi therapies, Onpattro is an IV drug given every three weeks, while Tegsedi is a weekly self-administered injection under the skin. But Tegsedi carries a boxed warning on low platelet counts.

During Alnylam’s first-quarter call in May, executives said some patients start on Ionis’ rival Tegsedi because of its convenience, but then switch to Onpattro. In the first quarter, Onpattro brought in $26.3 million, beating analysts’ expectations of $19 million. In the same period, Tegsedi’s first full quarter on the market, the drug generated $7 million.

In the EU, both drugs face competition from Pfizer’s tafamidis, which has been approved in Europe for years in polyneuropathy, and the fight could spread to the U.S. soon.

The Pfizer drug, now marketed as Vyndaqel and Vyndamax, snatched up an FDA nod in May to treat both hereditary and wild-type ATTR patients with a heart condition called cardiomyopathy. And next up, analysts say, Pfizer is hoping to move into Tegsedi and Onpattro’s realm with a polyneuropathy approval on par with theirs.

Alnylam’s data offer a glimpse into the potential competition ahead. In the Apollo study, about one-third of patients were previously treated with the Pfizer drug. These pre-treated patients also experienced significant improvement in polyneuropathy and quality of life after 18 months, Alnylam said.