Oct 29, 2026 earnings call — TTR franchise growth and TRITON-CM enrollment expansion
Alnylam expanded TRITON-CM enrollment to approximately 2,250 patients to strengthen study power.
Revenue $1.5B (est $1.4B) · EPS $16.26 (est $1.66)
Key quotes
"Importantly, AMVUTTRA has broad and favorable access, with approximately 99% of covered lives having access and approximately 90% of patients able to receive treatment within approximately 10 mi of where they live."
"As such, we are announcing today that we are amending the protocol to further increase the sample size by 500 patients to a total of 2,250 patients to address the potential risk of lower than expected event rates."
"Across two assays, we saw mean maximum reductions of CSF mutant huntingtins of 60%-64%, with individual reductions up to 83%."
Analyst Q&A 9
TRITON-CM study design changes
Q (Kostas Biliouris · Oppenheimer): He asked what other changes were considered for TRITON-CM, for example changing the primary endpoint, and whether more changes are expected or if this is final.
A: Management said their expectations for nucresiran's effect did not change. They added 500 patients to ensure enough events and power as background event rates fall, and said analytic tweaks could be made later in a blinded fashion while enrollment continues.
"I think the change that we made today is as we, again, look at evolution in event rates in the background as this patient population is better and better treated and earlier and earlier diagnosed." — Pushkal Garg
AMVUTTRA demand vs physician outreach
Q (Ellie Merle · Barclays): She asked why increased physician engagement from the expanded field force has not yet translated into faster patient demand, what hurdles remain, and whether this is a lag or other issue.
A: Management said reach and engagement are increasing and they now have 2,000 active prescribers. Converting those prescribers into patient starts is slower because newer physicians have fewer cardiomyopathy patients, less disease familiarity and more entrenched habits; they are intensifying interactions and services to build familiarity and expect no acceleration in Q4 2026.
"As I said, look, we're not satisfied with the pace of AMVUTTRA demand growth, and we need to do better." — Yvonne Greenstreet (CEO)
340B rule: price vs demand risk
Q (Paul Matteis · Stifel): He asked whether the proposed 340B rule would only lower net price or could also disrupt demand, new starts, or cause patient switches at 340B institutions.
A: Management said they are focused on patient access and keeping 340B institutions economically viable. They listed contracting with health systems and alternate sites of care (third-party infusion clinics, home) as options, said it is difficult to predict impact until the rule is finalized, and that impacts on gross-to-nets and volume are possible.
"There could be impacts on gross to nets, either positive or negative based on the choices they make, and there could be impact on volume." — Jeff Poulton (CFO)
340B exposure and bypass options
Q (Salveen Richter · Goldman Sachs): He asked how large 340B exposure is and whether Alnylam can bypass 340B with its own discounts when covered entities are involved.
A: Management said 340B is a meaningful portion of their business but they would not quantify it today. They described options: contracting with systems or enabling alternate sites of care; health systems could stay in 340B, shift to WAC purchasing, or move patients outside the system to third-party clinics or home.
"I think in terms of 340B in our business, it's a meaningful portion of our business." — Jeff Poulton (CFO)
Delay of HHT and obesity data
Q (Whitney Ijem · Canaccord Genuity): She asked why HHT and obesity data were delayed to February with Q4 earnings and whether the data content changed with the delay.
A: Management said there was no change in timelines and the studies are on schedule; they will report at the Q4 year-end call. For ALN-2232 (ACVR1C) obesity they will show knockdown and safety plus some weight and visceral fat measures; for ALN-6400 (HHT) they expect initial proof of concept efficacy and safety data early next year.
"Maybe just to put a little context around, there has been really no change in our overall timelines for either of those studies." — Pushkal Garg
Huntington's program path and brain delivery
Q (Joon Lee · UBS): He asked what clinical events will guide Huntington's development, whether filing will be a BLA or NDA, and thoughts on a transferrin receptor conjugated siRNA for CNS.
A: Management said brezosiran will move to phase III and the program will be filed as an NDA. They are focused on achieving deep knockdown throughout the brain including deeper structures like the caudate, ensuring durability and tolerability, continuing dose exploration in phase I, and they are also researching peripheral brain-shuttle approaches.
"We again want to maintain and ensure deep knockdown throughout the brain, including the deeper structures in the caudate." — Pushkal Garg
Enriching TRITON patients and powering
Q (Ritu Baral · TD Cowen): She asked how they will reduce patient severity in TRITON beyond proBNP, how they will enrich the population, and what impact the extra 500 patients has on powering and assumed event rates.
A: Management said they will enroll earlier disease patients often defined by NAC stage, which is heavily weighted by NT-proBNP, and use other entry criteria like history of events to find patients likely to benefit. They would not give detailed event-rate numbers, but said they have been conservative in trial assumptions and with 2,250 patients are well-positioned and well-powered under conservative event-rate assumptions.
"That earlier disease population is often defined by NAC stage, which really is heavily weighted based on NT-proBNP." — Pushkal Garg
Model inputs to stress for 340B rule
Q (David Lebowitz · BMO): He asked which parts of models (top and bottom line) to stress-test for potential impacts from the 340B regulation.
A: Management said the main implication is net price: if providers stay in 340B purchasing it would increase gross-to-net and lower net price; if systems move to WAC or patients move to alternate sites it would be positive to net price. They cannot predict provider choices or volume impact yet and will wait for January experience before commenting further at year-end.
"If the providers stay in the traditional 340B purchasing channel, that would increase gross to nets, move net price down, because we would be providing a discount below the current statutory 340B rate." — Jeff Poulton (CFO)
2030 revenue CAGR outlook question
Q (Luca Issi · RBC): He asked whether the 25%+ total revenue CAGR through 2030 still looks achievable given recent changes (second-line bolus, 340B proposal, Medicare Advantage policy).
A: Management said Alnylam 2030 is a broad plan and they are nine months in with progress across launch, TRITON-CM, and pipeline. They reiterated the AMVUTTRA launch is early with opportunity, stated the U.S. treated ATTR-CM population is expected to grow to about 75,000 patients by 2030, said they aim for a third of the category TRX and are at 24% TRX now, and said capturing that share plus ex-U.S. growth would support their ambitions while they navigate near-term demand and payer changes.
"We see significant opportunity ahead, and we're investing against that to broaden the prescriber base." — Yvonne Greenstreet (CEO)