Alnylam Pharmaceuticals, Inc. Q2 FY2025 earnings call

• TTR leadership: Launch of AMVUTTRA is off to a strong start, with ~1,400 cardiomyopathy patients receiving AMVUTTRA as of June 30, and international markets expected to contribute to CM launch in the second half of the year.
• Growth through innovation: Pushkal Garg promoted to Chief Research and Development Officer. Initiated TRITON-CM Phase III study of nucresiran, FDA granted Fast Track Designation to nucresiran for ATTR-CM. Shared Phase I multi-dose data for mivelsiran in Alzheimer's disease and kicked off Phase I study for ALN-4324 in type 2 diabetes.
• Strong financial performance: Reported strongest quarter to date with $672 million in total net product revenues, 64% growth year-over-year. Increased net product revenues guidance for 2025 from $2.05B - $2.25B to $2.65B - $2.8B.

Rare franchise: Combined Q2 sales of GIVLAARI and OXLUMO were $128 million, up 24% versus last year. Growth was largely demand driven with a tailwind from favorable GIVLAARI gross-to-net adjustments in the U.S. TTR franchise: Global net product revenues were $544 million during the quarter, a 77% increase compared with Q2 2024 and a 51% increase compared with Q1 2025. In the U.S., combined Q2 sales of ONPATTRO and AMVUTTRA rose 80%, up roughly $170 million from Q1, driven primarily by AMVUTTRA's ATTR-CM launch. The U.S. TTR franchise achieved $383 million in the second quarter, a 80% quarter-over-quarter growth. International markets saw 18% year-over-year growth in TTR franchise, but no ATTR-CM revenue was recognized internationally yet with launches in Germany and Japan slated to contribute in the third quarter.

• Increased net product revenue guidance from $2.05 billion to $2.25 billion range to $2.65 billion to $2.8 billion range, representing a $575 million or 27% increase at the midpoint.
• Modestly increase the midpoint of total Rare franchise guidance by raising the bottom end of prior guidance range by $25 million and leaving the top end unchanged, resulting in revised Rare product sales guidance of $475 million to $525 million.
• Materially increase total TTR guidance range from $1.6 billion to $1.725 billion to $2.175 billion to $2.275 billion, representing a 34% increase or more than $550 million at the midpoint.

Q: Could you give some details here on the patient profiles for AMVUTTRA with regard to the frontline patients and whether you're seeing mostly mixed phenotype patients or more of a broader population mix?

A: Yvonne Greenstreet said it's early days, but pleased with launch progress. Seeing broad uptake across first-line patients as well as patients that progress on stabilizers, across community and academic physicians, new and repeat prescribers. Initial pickup faster in stabilizer progressing patients but now achieving healthy share of first-line patients.

Q: How are you thinking about net price for AMVUTTRA and gross-to-net moving forward?

A: Jeff Poulton said expected mid-single-digit reduction in net price for AMVUTTRA in 2025. Tolga Tanguler added payer dynamics moving as expected, with broad payer coverage and patients paying minimal out-of-pocket costs in most cases.

Q: Can you speak a little more in a little more detail to the assumptions underpinning the updated TTR franchise guidance as it relates to like the pace of new starts?

A: Tolga Tanguler said seeing steady growth in first line and second-line patient flow. Initially uptick concentrated in stabilizer progressors but now seeing healthy and accelerating trend in first-line use. Current guidance reflects this. Jeff Poulton added context on guidance, highlighting year-over-year growth implication for TTR.

Q: As it relates to stabilizer progressors, can you talk a little bit more about the criteria physicians are using?

A: Tolga Tanguler said based on research and published data, clinical evidence suggests 1/3 to half of patients on stabilizer progress. Pushkal Garg added that doctors look at a variety of factors like biomarkers, echocardiographic factors, exercise tolerance, etc. in determining patient progression.

Q: Congrats on the strong quarter. Maybe if I can circle back on the TTR guide, maybe, Jeff, like if I assume $200 million in revenue for the year from ONPATTRO, that essentially means $550 million to $650 million in revenues for the next 2 quarters for AMVUTTRA...

A: Jeffrey Poulton said reiterated guidance, guiding to $1 billion of TTR growth year-over-year, feeling confident about the guidance provided.

Q: Congrats on the strong launch. One question on payers from us, although you already touched a little bit on that. We have seen some commercial payers requiring stabilizer use prior to AMVUTTRA treatment in cardiomyopathy. Can you comment on how common those requirements are across the different plans?

A: Yvonne Greenstreet said access is not a barrier, seeing broad coverage across Medicare fee-for-service, Medicare Advantage, commercial payers. Tolga Tanguler added that step edit policies are minimal, in single digits, and not anticipated to grow significantly.