Alnylam (ALNY) Q1 2025: TTR Franchise Soars 36% as ATTR-CM Launch Accelerates Access

May 1, 2025 | By EarningsIQ Research

Alnylam’s Q1 marked a pivotal inflection, with its TTR franchise up 36% and the ATTR cardiomyopathy (ATTR-CM) launch establishing broad early access across U.S. health systems. Robust execution in both hereditary and new cardiomyopathy indications underpins management’s confidence in achieving sustainable profitability in 2025. Investors should monitor formulary expansion and real-world patient uptake as key catalysts for the second half and beyond.

Summary

• ATTR-CM Launch Momentum: Early U.S. launch of Ambutra in cardiomyopathy indication rapidly expanded formulary access and patient initiations.
• Rare Disease Franchise Steady: Rare disease products delivered double-digit patient growth, supporting portfolio diversification.
• Profitability Pathway: Management reiterates 2025 non-GAAP profitability goal, leveraging disciplined capital allocation and robust gross margins.

Performance Analysis

Alnylam delivered $469 million in Q1 product revenues, up 28% year-over-year, propelled by a 36% surge in the TTR franchise, which now anchors the company's growth narrative. The U.S. TTR business, including Onpatro and Ambutra, led with 45% growth, underscoring effective commercial execution even as new competitors entered the market. Notably, the ATTR-CM indication for Ambutra was approved with only days left in the quarter, so Q1 revenue reflects hereditary polyneuropathy (PN) demand, not the new cardiomyopathy launch.

Rare disease products Givlari and Oxlumo contributed $109 million, with 8% revenue growth and patient counts up 15% and 20% respectively. Gross margin remained robust at 85%, though management flagged that royalty rates on Ambutra will escalate through the year, pressuring margins. Non-GAAP R&D spend was flat, as new trial investments offset Helios-B wind-down, while SG&A rose 12% to support the ATTR-CM launch. Operating profit improved sharply, aided by top-line momentum and cost discipline.

• TTR Franchise Outperformance: U.S. TTR revenue grew 45% YoY, capturing 70% of new PN patient starts despite new competition.
• Rare Disease Expansion: Patient growth outpaced revenue due to European gross-to-net adjustments and partner order timing.
• Margin Dynamics: Gross margin held steady but is expected to decline as Ambutra royalty tiers escalate with sales volume.

Alnylam’s base business shows resilience and pricing power, while the ATTR-CM launch sets up a second-half revenue acceleration as formulary access and payer coverage scale.

Executive Commentary

Strategic Positioning

1. TTR Leadership and Differentiation

Alnylam’s strategy centers on establishing Ambutra as the standard of care in both hereditary and cardiomyopathy forms of ATTR. The ATTR-CM launch leverages a unique RNAi mechanism—distinct from stabilizer competitors—offering rapid TTR knockdown and quarterly HCP-administered dosing that ensures adherence. Early adoption is broad, spanning both existing and new prescribers, and Ambutra is already on formulary in more than half of key U.S. health systems within weeks of approval.

2. Access and Payer Strategy

Formulary inclusion and payer coverage are foundational to the launch’s trajectory. About 80% of TTR volume flows through 170 health systems, and Ambutra secured formulary status in over half within four weeks. The majority of patients face zero copay, and value-based agreements are in place across payer segments. Medicare fee-for-service patients face minimal access barriers, with commercial and Medicare Advantage patients also seeing broad uptake and limited step edits or prior authorization requirements to date.

3. Innovation Pipeline and Lifecycle Management

Pipeline execution remains a priority, with pivotal studies for next-generation Nucresiran in ATTR-CM and hereditary PN slated for 2025. The company also initiated new clinical programs in type 2 diabetes and bleeding disorders, aiming to expand RNAi’s reach into high-value, high-unmet-need indications. Delivery platform advancements target broader tissue access, supporting a 2030 vision to reach every major tissue with RNAi therapeutics.

4. Financial Discipline and Profitability Focus

Alnylam is committed to achieving sustainable non-GAAP profitability in 2025, balancing commercial expansion with disciplined R&D and SG&A investment. The company’s cash position remains strong, and management signaled that current tariffs and FX volatility are manageable within guidance, supported by a U.S.-centric manufacturing and IP base.

Key Considerations

This quarter’s results reflect a company at a strategic inflection, with a new blockbuster indication launching into an expanding category. Investors should weigh:

• Formulary Penetration Pace: Early Ambutra access in health systems is tracking ahead of plan, setting up a strong second-half pull-through.
• Category Expansion: With 80% of the global ATTR population untreated, increased awareness and new therapies are accelerating diagnosis and treatment rates.
• Competitive Dynamics: Despite new stabilizer entrants, Ambutra maintained 70% share of new PN starts, highlighting brand strength and clinical differentiation.
• Pipeline Risk and Opportunity: Next-generation programs (Nucresiran, Zalbiceran) could extend the franchise, but require successful pivotal trials and regulatory milestones.
• Royalty and Margin Pressures: Rising Ambutra royalties will weigh on gross margin as sales grow, requiring continued SG&A discipline to offset.

Risks

Key risks include execution on the ATTR-CM launch, particularly sustaining broad payer and formulary access as patient volumes ramp. Royalty rate escalation will pressure margins, and pipeline timelines (notably for Nucresiran and Zalbiceran) could slip. While management downplays tariff and regulatory headwinds, evolving policy and reimbursement frameworks remain a wildcard. Competitive responses from stabilizers or new entrants could also blunt Ambutra’s growth trajectory.

Forward Outlook

For Q2 2025, Alnylam expects:

• ATTR-CM launch to drive sequential revenue acceleration as formulary access and patient initiations scale.
• Continued robust growth in the TTR franchise, supporting full-year guidance.

For full-year 2025, management reiterated guidance:

• 36% TTR franchise revenue growth at the midpoint
• Sustainable non-GAAP profitability

Management emphasized that FX trends could provide up to $50 million upside to product sales if current rates persist, and that additional ATTR-CM approvals in Japan and Europe are anticipated in Q2 and Q3, respectively.

• Second-half growth will hinge on further formulary wins and real-world patient uptake.
• Pipeline catalysts, including Nucresiran and Zalbiceran trial initiations, remain on track for 2025.

Takeaways

Alnylam enters a new phase, with the ATTR-CM launch driving both near-term growth and long-term franchise durability. Investors should focus on:

• ATTR Franchise Expansion: Early launch execution and broad health system access position Ambutra for significant share gains in a largely untreated market.
• Operational Leverage: Sustained revenue growth, combined with cost discipline, supports the path to profitability even as royalty rates climb.
• Pipeline Execution: Progress on next-generation RNAi therapeutics and new indications will be critical for maintaining momentum beyond 2025.

Conclusion

Alnylam’s Q1 results confirm the company’s transformation into a TTR-focused commercial powerhouse, with rapid progress in ATTR-CM access and robust rare disease growth. The second half will be defined by real-world uptake and pipeline execution, making this a pivotal year for long-term value creation.

Industry Read-Through

Alnylam’s rapid formulary penetration and payer alignment for Ambutra in ATTR-CM signals that U.S. health systems are increasingly receptive to new mechanisms and value-based agreements in rare and specialty indications. The RNAi platform’s expanding reach—now targeting diabetes and bleeding disorders—underscores the broadening competitive threat to both legacy biologics and small molecules. For biopharma peers, the ATTR-CM launch illustrates the importance of health system engagement, patient support infrastructure, and payer strategy in unlocking blockbuster potential for differentiated therapies.

ALNY Healthcare Biotechnology Rare Disease RNAi TTR Franchise ATTR-CM Profitability