Alnylam Pharmaceuticals

Alnylam posted second-quarter net product revenue of nearly $1.2 billion, up 74% compared with the prior-year period, driven by total ATTR franchise sales exceeding $1 billion. Management cut its 2026 ATTR sales guidance by $200 million at the midpoint and shares fell 28% on July 30.

Why it matters: This was the first quarter in which Amvuttra surpassed $1 billion in sales, and the drug has delivered impressive triple-digit revenue growth since its key US Food and Drug Administration approval for ATTR-CM in March 2025. Investors' sharp selloff is driven less by the quarter's performance and more by a reset in growth expectations as management acknowledged that Amvuttra's early launch success was boosted by pent-up demand that has since normalized. While growth expectations have been reset, prescribing patterns indicate that physicians who already prescribe Amvuttra are increasingly choosing it over competing therapies, with Amvuttra accounting for 50% of new patient starts. A key indicator will be whether new-patient demand continues to expand independently of switching activity.

The bottom line: We lowered our fair value estimate to $299 per share from $310 for narrow-moat Alnylam. Given the significant pullback, shares trade about 31% below our valuation. Ionis and AstraZeneca's recent phase 3 setback for their competing ATTR-CM silencer drug may remove a competitor, but it has also fueled broader skepticism toward the silencer class and clouded Amvuttra's positioning and the outlook for next-gen nucresiran. We assign nucresiran a 65% probability of approval and reiterate our High Uncertainty Rating for Alnylam. While we have reduced our growth expectations for Amvuttra, we had already incorporated market share pressure and pricing headwinds associated with intensifying competition in ATTR over our 10-year forecast period.

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We lowered our fair value estimate to $299 per share, down from $310, for narrow-moat Alnylam.

Management cut its 2026 ATTR sales guidance by $200 million at the midpoint, and we now forecast about 44.35 billion in ATTR sales for the year. While we have reduced our growth expectations for Amvuttra, we had already incorporated market share pressure and pricing headwinds associated with intensifying competition in ATTR over our 10-year forecast period.

Our valuation rests on the approval and commercial success of Alnylam's RNAi therapies. We forecast Amvuttra will help expand the company's revenue thanks to its subcutaneous injections administered once every three months for patients with ATTR amyloidosis with polyneuropathy, compared with Onpattro's intravenous infusion once every three weeks.

Ionis and AstraZeneca's phase 3 setback for their competing ATTR-CM silencer drug may remove a competitor, but this has also fueled skepticism toward the silencer class more broadly and has clouded Amvuttra's positioning and next-gen nucresiran's outlook. We assign nucresiran a 65% probability of approval and reiterate our High Uncertainty Rating for Alnylam. We anticipate Alnylam could generate peak ATTR franchise sales of $7.3 billion, including combined sales of Onpattro, Amvuttra, and probability-weighted sales of nucresiran.

Givlaari for AHP and Oxlumo for primary hyperoxaluria will also help drive returns, given that Alnylam has full global rights for both assets. We anticipate Givlaari could reach peak sales of over $800 million while Oxlumo's sales could reach roughly $350 million. We continue to expect strong geographic expansion efforts will be a key driver for Onpattro, Givlaari, Oxlumo, and Amvuttra, which should lead to substantial growth for the firm.

Alnylam reported positive phase 3 results for cemdisiran (generalized myasthenia gravis) and a submitted US filings in 2026. We assign this candidate an 85% probability of approval, and and we anticipate it could reach the market in 2027. We assign phase 3 candidate zilebesiran (for hypertension) a 75% probability of approval, and we anticipate it could launch as early as 2028. We forecast robust, double-digit total company revenue growth in the near term.

Alnylam reached profitability in 2025 for the first time since its founding in 2002, recording nearly $314 million in net income and diluted EPS of $2.33 in 2025. We expect collaboration partnerships and cash flows from Alnylam's TTR franchise will help mitigate the hefty operating expenses required to advance candidates through clinical development. We assume a 9.1% cost of equity for Alnylam, which is consistent with the other emerging biotech companies under our coverage.

We assign Alnylam a Morningstar Economic Moat Rating of narrow, based on the intangible assets of its RNA interference, RNAi, technology and its lengthy patents. Alnylam's proprietary technology specializes in RNAi, which uses small interfering RNA to silence malfunctioning genes. Its technology has led to a new class of therapies, which are prime for targeting rare diseases and other disorders caused by genetic mutations. Alnylam's RNAi technology platform has produced four marketed products since 2018, along with a growing and diverse pipeline, which supports the company’s intangible assets and narrow economic moat. In addition, Alnylam has lengthy patents for its drugs extending well into 2035. Alnylam reached returns above its cost of capital in 2025, and we model-adjusted ROICs averaging 35% during our 10-year forecast period, versus a 9.1% WACC.

Onpattro (patisiran) was approved in 2018 for polyneuropathy in hereditary ATTR amyloidosis, a rare, progressive disease characterized by the abnormal buildup of amyloid deposits in the body’s organs and tissues. Alnylam has a dominant position within the hATTR amyloidosis market, and it has been able to build upon its RNAi expertise to create a highly effective drug. One of Alnylam's primary competitors, Ionis Pharmaceuticals, competes in this space with its own RNA-based technology platform. Ionis' drug, Tegsedi (inotersen), was approved shortly after Onpattro for the same indication, but its label carries a black-box warning for thrombocytopenia and glomerulonephritis requiring frequent monitoring. This weaker safety profile has kept Tegsedi from competing effectively against Onpattro, illustrating the competitive edge of Alnylam's RNAi platform.

Other competitors include Pfizer's Vyndaqel/Vyndamax (tafamidis) and BridgeBio's Attruby, both small-molecule transthyretin stabilizers approved in ATTR-CM, a distinct indication from the polyneuropathy space where Onpattro and Tegsedi compete.

The FDA approved Alnylam's Amvuttra in 2022 for ATTR amyloidosis with polyneuropathy, and in March 2025, the FDA approved Amvuttra as the first RNAi therapeutic for adults with ATTR-CM. ATTR-CM is estimated to affect more than 250,000 people globally, but many are underdiagnosed, while ATTR-PN is a much rarer disease affecting about 10,000-40,000 people globally. Many ATTR amyloidosis patients may have both cardiomyopathy and polyneuropathy, and both are commonly misdiagnosed or underdiagnosed. Amvuttra is a quarterly subcutaneous injection as opposed to Onpattro's intravenous injection every three weeks, which makes dosing less burdensome for patients.

Regeneron and Intellia Therapeutics are co-developing a CRISPR-Cas9 gene-editing ATTR therapy; while early data showed a strong mean TTR reduction, longer-term safety data in larger patient populations is still needed. Alnylam already has a solid position within the ATTR amyloidosis market, and we anticipate several more years of expansion following Amvuttra's ATTR-CM approval in 2025.

Givlaari (givosiran) is approved in the US, EU, and other markets for acute hepatic porphyria, or AHP, a family of rare genetic diseases with a high unmet need that supports strong pricing power. AHP's symptoms are frequently misdiagnosed as more common conditions, and Alnylam's disease-awareness efforts and patient-group engagement should support diagnosis rates and market penetration over time.

Oxlumo (lumasiran) is approved in the US and EU for primary hyperoxaluria type 1, a rare genetic metabolic disorder that can result in kidney and liver failure, and Alnylam continues to expand its global commercial footprint and regulatory filings for the drug.

Alnylam also has partnered programs in which it receives royalties or a share of profits if the drug candidate is approved. Leqvio (inclisiran), developed in partnership with Novartis and Blackstone, targets hypercholesterolemia, or high cholesterol, via twice-yearly subcutaneous injections. Leqvio provided LDL cholesterol reductions of up to 52% in its clinical program and looks competitive against statins and PCSK9 inhibitors like Amgen's Repatha and Regeneron/Sanofi's Praluent, offering dosing convenience with only twice-yearly injections versus every two weeks or monthly. Alnylam is eligible for royalties up to 20% on Leqvio sales, benefiting from partnered programs where larger companies bear development and commercialization costs while Alnylam earns tiered royalties and preserves resources for its RNAi pipeline.

Alnylam's Nobel-prize-winning technology and massive intellectual property in RNA interference helped the firm create an entirely new class of therapeutics for difficult to treat diseases.

Alnylam's full pipeline offers several opportunities to bolster the company's competitive position, and it indicates a reproducible research strategy.

Onpattro is the first approved RNA interference therapy. In addition to first-mover advantage, Alnylam has expanded its reach in ATTR amyloidosis with next-generation Amvuttra, which is administered less frequently.

Alnylam's valuation rests on its ability to maintain six-figure pricing and payers' willingness to continue reimbursement, which could be affected by shifts in healthcare drug policy.

While Alnylam is targeting several rare genetic disorders—including amyloidosis, AHP, and complement-mediated diseases—entrenched competitors are also progressing next-generation treatments.

As is the case with most orphan diseases, if Alnylam cannot successfully raise awareness of these underdiagnosed diseases and improve diagnosis rates, its commercial success will be limited.