Alnylam (ALNY) Q2 FY26 earnings call: guidance and Q&A

Given the revised guidance and previous 2030 CAGR target, how confident is management in maintaining growth, especially in the next 12-24 months, and meeting long-term goals?

Management acknowledged the guidance cut but emphasized strong fundamentals, first-line momentum, and increased confidence due to competitive developments (eplontersen failure, tafamidis LOE). They stated that Q3 and Q4 growth needs to be consistent with Q2 to meet the revised FY26 midpoint. The 80% untreated market, strong first-line base, and expanding prescriber base support long-term confidence.

“Clearly, we're not pleased to be lowering guidance, as Jeff said, we own it. But I think it's really important to emphasize that we believe that the fundamentals driving our opportunity a really strong, particularly market growth in our first-line momentum.”

asked by Paul Matteis · answered by Yvonne Greenstreet

Is there a slower rate of second-line patients (TAF progressors) due to earlier diagnosis? How will diagnosis and awareness efforts impact first-line capture?

Tolga confirmed the normalization of second-line demand after initial pent-up demand. He emphasized that early diagnosis will help increase and accelerate overall category growth, which has already been observed since launch, creating a tailwind for first-line treatment.

“Frankly, the when we started just like any launch when you have an artogonol mechanism of action product like we do, we knew that there was going to be a level of pent-up demand. And it certainly, over time, we've seen that being normalizing.”

asked by Tommie Reerink · answered by Tolga Tanguler

With 80% first-line starts, what is the split between community and Centers of Excellence (COE) practices? How will Alnylam maintain first-line growth given potential physician perception of similar efficacy between silencers and stabilizers?

Tolga clarified that the 80/20 split reflects an overall category shift, not market share loss in second-line. He noted that growth is driven by first-line share and deepening adoption in existing accounts, with a healthy balance of COEs and community experts. Pushkal added that AMVUTRA has a unique profile with remarkable outcomes and additive benefits over stabilizers, which they will continue to educate physicians on.

“What's been really encouraging for us is, as we establish that early base business, that business didn't just come from the COEs. We actually had a very healthy balance of COEs academic centers as well as community experts.”

asked by Tazeen Ahmad · answered by Tolga Tanguler

Given VYNDAQEL's upcoming generic entry in Europe, to what extent will European commercial dynamics between AMVUTRA and generics reflect what might happen in the U.S. post-2031 when tafamidis goes generic?

Tolga stated that Europe's growth contribution will be modest. He noted that in Europe, they have secured premium pricing for AMVUTRA versus tafamidis generics in single-payer systems. He believes launches in 2027 and beyond will have a meaningful impact, but did not directly compare to the U.S. post-2031.

“Now in respect to our ability to actually capture those reimbursements since these are single-payer systems, these systems have already anticipated that genericization transition. And what I'm pleased to say that we've actually, in most cases, been able to secure premium pricing versus tafamidis and quite pleased with the ongoing negotiations we have, whether it's Germany, Spain, Italy.”

asked by Konstantinos Biliouris · answered by Tolga Tanguler

Is 20% a steady-state for second-line starts? What drives confidence in first-line cadence, and are first-line starts growing or stable?

Tolga clarified that the 80/20 split refers to the overall category, not a market share loss in second-line. He emphasized that AMVUTRA's market share growth is now driven by first-line share. Physicians who use all three products predominantly choose AMVUTRA as their first-line option, and the focus is on expanding the prescriber base.

“And in respect to the first line contributions, as I alluded to earlier, those physicians that actually use all 3 products predominantly used AMVUTRA is their first time choice. That's the analysis that we have.”

asked by Eli Merle · answered by Tolga Tanguler

Is there any commercial impact from AstraZeneca's CARDIO-TTRansform data, specifically regarding payer pushback on combo therapy? What is the expected net price evolution for the U.S. for the rest of the year?

Tolga stated it's too early for payer pushback, but AMVUTRA access remains strong. Existing Medicaid Advantage policies limit combo use, but physicians can pursue access. He emphasized that CARDIO-TTRansform does not change AMVUTRA's evidence or label. Jeff Poulton confirmed modest Q-o-Q net price decreases are expected to continue, on track for a mid-single-digit YoY decrease.

“What's also very important is CARDIO-TTRansform does not change ultra's evidence or its label. It was a study of a different molecule. We would not expect payers to offer alter AMVUTRA coverage based on those results.”

asked by Luca Issi · answered by Tolga Tanguler

Can Pushkal elaborate on potential changes to TRITON-CM to maximize success, and are there alternative paths to approval for nucresiran in ATTR-CM, such as a non-inferiority trial against AMVUTRA?

Pushkal stated they may not need to change anything but options include modifying enrollment in subpopulations (enrichment) and adjusting the analytic plan (endpoints, hierarchy). He confirmed the possibility of additional studies but declined to speculate on specifics, emphasizing commitment to a successful study for nucresiran.

“I think they broadly fall into a couple of buckets. One is whether we modify enrollment in certain subpopulations, for instance, and enrich in certain ways for those -- again, we've done that already in the context of the study, but we could potentially further do that based on formation that we see.”

asked by Jessica Fye · answered by Pushkal Garg

Can management provide updated thinking on the total U.S. patient population or TAM for ATTR-CM and current diagnosis rates? What are the comparable numbers for HHT (ALN-6400) U.S. TAM and diagnosis rate?

Tolga estimated around 200,000 ATTR-CM patients in the U.S., with 80% untreated, and the category growing 40% YoY. Pushkal estimated ~1.5 million global HHT patients, with ~70,000 addressable in the U.S., noting that epidemiology firms up as effective treatments become available.

“So for TTR, what I can tell you is in our less system, if you go back to our TTR webinar, we've highlighted, we estimate around 200,000 patients and about 80% of those remain untreated.”

asked by Whitney Ijem · answered by Tolga Tanguler