Alnylam’s closely watched launch of its rare disease drug Amvuttra continued to outpace Wall Street expectations.
Riding its March expansion into the heart condition of transthyretin amyloid cardiomyopathy (ATTR-CM), Amvuttra generated $685 million sales in the third quarter. The haul came 11% above analysts’ consensus estimates, according to a Jefferies note Oct. 27.
Thanks to the strong performance, Alnylam has increased its full-year sales guidance again, now expecting total TTR franchise revenues in a range between $2.475 billion and $2.525 billion, a $275 million (10%) increase at midpoint.
Alnylam's overall product revenue of $851 million for the period beat analysts’ consensus by 8%, according to a Thursday note from Evercore ISI.
Despite the beat, Alnylam’s stock price was down about 7% as of 11 a.m. Eastern Time. The drop is likely explained by lofty investor expectations that Amvuttra would reach $695 million to $700 million in the quarter, William Blair analysts said in a Thursday note about a similar premarket stock move.
The Jefferies team, which was more bullish on Amvuttra’s performance than consensus, previously pegged Alnylam’s TTR franchise to reach above $2.6 billion this year, according to an earlier note. In the Oct. 27 note, the team put its Amvuttra third-quarter projection at $732 million, markedly above consensus.
ATTR-CM patient demand for Amvuttra about doubled in the U.S. in the third quarter versus the previous three months that ended in June. That expansion shows “a very healthy sign” of Amvuttra’s launch progression, Alnylam’s chief commercial officer Tolga Tanguler said in an interview with Fierce Pharma.
Back in the second quarter, which was Amvuttra’s first full quarter on the ATTR-CM market, Tanguler reported the initiation of 1,400 ATTR-CM patients on Amvuttra and about $150 million revenue in the specific indication. Back then, Amvuttra’s $492 million quarterly sales handily beat analysts’ expectations by 40%. Besides ATTR-CM, the RNA interference therapy is also approved since June 2022 in ATTR-polyneuropathy, another subtype of the TTR protein disorder that affects the nervous system.
Because Amvuttra is reimbursed under the buy-and-bill model and healthcare facilities keep stocking the drug using the same code regardless of its end application, it’s difficult to separate specific contribution of each indication to Amvuttra, Tanguler explained.
Still, Tanguler described a “very steady” ATTR-PN business. Based on an approximately doubling of ATTR-CM patient demand, Tanguler said it “would be safe to assume” that U.S. sales from ATTR-CM uses also roughly doubled sequentially to about $300 million in the third quarter.
Some of the strong momentum that Alnylam reported in the second quarter remained in effect in the third quarter, according to Tanguler.
“What we’re really seeing is, first of all, a […] balanced and broad demand,” Tanguler said.
Amvuttra, a TTR silencer, is competing with Pfizer’s mainstay Vyndamax and BridgeBio’s newer TTR stabilizer Attruby. Wednesday, BridgeBio reported third-quarter Attruby revenue of $108 million in the U.S. and 5,259 unique patient prescriptions as of Oct. 25.
Amvuttra is “highly competitive” in first-line treatment, which is “a very good signal of the robustness and the health of the business,” Tanguler said.
“Doctors want to treat this early and hard,” Tanguler observed, pointing to an emerging theme where physicians would use Amvuttra upfront rather than wait until patients have progressed on an oral stabilizer.
There have been some combination uses in the commercial setting, including in patients who have mixed ATTR-CM and -PN phenotypes, but Tanguler again said it’s not the main driver of Amvuttra uses.
The drug is gaining traction in both academic centers and in the community setting, where Alnylam has established alternative sites of care from which patients can receive the quarterly injection closer to their homes, Tanguler said. About 90% of the patients have access to these sites of care within 10 miles, he added.
Moreover, Alnylam has set up treatment processes at all the approximately 170 priority health systems for Amvuttra, and the company is now “going deeper in those centers,” he added.
Outside of the U.S., Amvuttra got an ATTR-CM approval from the European Commission in June, and it’s also cleared in Japan.
Alnylam is still in early stages of the ATTR-CM launch ex-U.S. with availability only in Germany and Japan so far, Tanguler said. In Germany, where price negotiations are ongoing, Tanguler described “more of a softer launch” in the European country.
“But in Japan, I’m really encouraged,” the Alnylam CCO said. “We’re seeing a step change. Granted, it’s relatively a small market right now, but when I think of the analogs of similar type of products and specialty and how those products have picked up, we're seeing a very nice, robust, very competitive uptake that is, frankly, category defining.”
Alnylam recently updated 48-month data from the phase 3 Helios-B trial that earned Amvuttra its ATTR-CM approvals. On time to first cardiovascular event or all-cause mortality, four years of Amvuttra treatment led to a 37% relative risk reduction compared to patients who received placebo first and then Amvuttra in the open-label extension period. For patients who were not on any background TTR silencer, the treatment effect was bigger, at 42%. For death risk specifically, continuous Amvuttra led to a 37% reduction in the overall population versus 39% in the monotherapy population.
While the new data set “seems to really resonate,” Tanguler said, “we need more time for the market to start actually really understanding and appreciating this. And again, I like where we are. We’re building the right momentum. But it’s going to take us some time to continue to establish our dominance.”
Editor's Note: The story was updated 11a.m. Eastern Time to include Alnylam's stock price movement and overall product revenues.