Alnylam Pharmaceuticals (ALNY) shares soared 11.8% in the last trading session to close at $283.34. The move was backed by solid volume with far more shares changing hands than in a normal session. This compares to the stock's 1% gain over the past four weeks.The sudden rise in the stock price can be attributed to the FDA approval of Alnylam's regulatory filing seeking the label expansion of its lead drug, Amvuttra (vutrisiran), for treating the cardiomyopathy of wild-type or hereditary transthyretin-mediat ...

Waiting is often the most frustrating part of biotech investing, as the stocks can drift without clear positive drivers, and such has been the case with Alnylam Pharmaceuticals, Inc. (NASDAQ: ALNY ) for much of the past year, withAnalyst’s Disclosure: I/we have a beneficial long position in the shares of ALNY, RHHBY either through stock ownership, options, or other derivatives. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alph ...

Core Viewpoint - Alnylam Pharmaceuticals received FDA approval for the label expansion of its lead drug, Amvuttra, to treat cardiomyopathy associated with transthyretin-mediated amyloidosis, marking a significant milestone as it becomes the first and only approved therapy for both ATTR-CM and hATTR-PN in adults [1][3][4] Company Overview - Amvuttra is an RNAi therapeutic previously approved for treating polyneuropathy associated with transthyretin-mediated amyloidosis in adults [2] - The drug generated sales of $970.5 million in 2024, reflecting a 74% year-over-year increase, driven by new patient treatments and switches from Onpattro [11] Clinical Data and Efficacy - The approval is based on positive results from the pivotal phase III HELIOS-B study, which met all primary and secondary endpoints with statistical significance [4] - Amvuttra demonstrated a reduction in mortality and cardiovascular events, while improving functional capacity, quality of life, and heart failure symptoms in ATTR-CM patients [6] Safety Profile - The safety profile of Amvuttra in the HELIOS-B study was consistent with its known profile for treating hATTR amyloidosis, with similar rates of adverse events between Amvuttra and placebo groups [7] Market Potential - Amvuttra enjoys near-universal insurance coverage for hATTR-PN, and similar coverage is anticipated for ATTR-CM, supported by strong clinical data [8] - Regulatory applications for Amvuttra's ATTR-CM indication are under review in the EU, Brazil, and Japan, with further applications expected in 2025 [9][10] Growth Prospects - Alnylam believes that Amvuttra has the potential to become the new standard of care for ATTR-CM, which could significantly expand the eligible patient population and drive substantial growth for the company [10]

Core Insights - The U.S. FDA approved Alnylam Pharmaceuticals' supplemental application for Amvuttra to treat adults with ATTR-CM, aiming to reduce cardiovascular mortality, hospitalizations, and urgent heart failure visits [1][2]. Group 1: Approval and Indications - Amvuttra is now the first and only FDA-approved therapy for both ATTR-CM and hATTR-PN in adults [2]. - ATTR-CM affects approximately 150,000 individuals in the U.S. and over 300,000 globally [2]. Group 2: Clinical Trial Results - The approval is based on the HELIOS-B Phase 3 clinical trial, which showed statistical significance on all 10 primary and secondary endpoints compared to placebo [3]. - Amvuttra reduced the risk of all-cause mortality and recurrent cardiovascular events by 28% during a treatment period of up to 36 months [3]. - Mortality was significantly reduced by 36% through 42 months in a secondary endpoint analysis [4]. - In the monotherapy population, Amvuttra reduced the risk of all-cause mortality and recurrent cardiovascular events by 33% and the risk of mortality by 35% through 42 months [4]. Group 3: Market Dynamics and Financials - Amvuttra in hATTR-PN is covered by insurers for around 99% of patients, with most paying nothing out-of-pocket, and similar coverage is expected for ATTR-CM [5]. - In 2024, Amvuttra sales reached $970.45 million, an increase from $557.84 million the previous year [6]. Group 4: Future Prospects - Marketing authorization applications based on HELIOS-B data are under review by several global health agencies, including the European Medicines Agency and the Brazilian Health Regulatory Agency [6]. - Alnylam plans to proceed with additional global regulatory submissions for vutrisiran in 2025 [6]. Group 5: Stock Performance - Following the approval news, ALNY stock rose by 8.46% to $274.98 [7].

Core Viewpoint - Alnylam Pharmaceuticals is focused on developing RNAi-based therapeutics, with a strong pipeline and increasing sales of marketed drugs driving significant stock price growth [1][2]. Marketed Drug Portfolio - Alnylam's lead drug, Amvuttra, generated sales of $970.5 million in 2024, reflecting a 74% year-over-year increase, primarily due to new patient starts and switches from Onpattro [4]. - The combined sales of Givlaari and Oxlumo reached $422.9 million in 2024, up 29% year-over-year [5]. - Alnylam collaborates with Novartis to market Leqvio, which is approved in over 100 countries and is undergoing late-stage studies for further label expansion [6]. Pipeline Development Programs - Alnylam is seeking label expansion for Amvuttra to treat ATTR amyloidosis with cardiomyopathy, with a decision expected from the FDA on March 23, 2025 [7][8]. - The company is developing cemdisiran in partnership with Regeneron for various indications, with exclusive rights granted to Regeneron for certain developments [9]. - Alnylam has regained full rights to mivelsiran for Alzheimer's disease and expects to report interim data in the second half of 2025 [10]. - Collaboration with Roche on zilebesiran has shown promising results in phase II studies, with further studies planned for 2025 [11][12]. Growth Potential - Successful development and commercialization of the pipeline candidates are expected to significantly boost Alnylam's growth [13].

Core Viewpoint - Alnylam Pharmaceuticals reported a strong performance in Q4 2024, with adjusted earnings surpassing expectations and significant revenue growth driven by product sales and collaborations [1][2][15]. Financial Performance - Adjusted earnings for Q4 2024 were 6 cents per share, compared to a loss of 21 cents expected by analysts and a loss of 77 cents in the same quarter last year [1]. - Total revenues reached $593.2 million, exceeding the Zacks Consensus Estimate of $570 million and reflecting a 35% increase from $439.7 million in the prior year [2]. - Net product revenues were $450.8 million, a 30% increase year over year, driven by strong demand for Amvuttra, Givlaari, and Oxlumo [3]. Collaboration Revenues - Revenues from collaborators amounted to $106.9 million, a 40% increase from the previous year, primarily due to collaborations with Regeneron and Novartis [4]. Product Sales - Amvuttra generated sales of $286.5 million in Q4 2024, up 63% year over year, and exceeded the consensus estimate of $280 million [11]. - Givlaari recorded sales of $64.6 million, a 9% increase year over year, although it missed the consensus estimate of $69 million [12]. - Oxlumo achieved sales of $43.6 million, reflecting a 33% year-over-year increase, but fell short of the consensus estimate of $44.8 million [12]. Expenses - Adjusted R&D expenses rose 3% year over year to $259.5 million, driven by increased clinical study costs [13]. - Adjusted SG&A expenses increased 39% year over year to $244.3 million, mainly due to heightened marketing efforts for Onpattro and Amvuttra [13]. Cash Position - As of December 31, 2024, cash, cash equivalents, and marketable securities totaled $2.69 billion, down from $2.78 billion as of September 30, 2024 [14]. Full-Year Results - For the full year 2024, total revenues were $2.25 billion, up from $1.83 billion in 2023, and the company reported a loss of 2 cents per share, an improvement from a loss of $1.61 in 2023 [15]. 2025 Financial Guidance - Alnylam expects net product revenues for key products to be between $2.05 billion and $2.25 billion in 2025, with collaboration revenues projected between $650 million and $750 million [17]. Pipeline Updates - Alnylam is seeking label expansion for Amvuttra to treat ATTR amyloidosis with cardiomyopathy, with a decision from the FDA expected on March 23, 2025 [18].

Core Insights - Alnylam Pharmaceuticals reported strong revenue growth and exceeded Wall Street expectations with a non-GAAP EPS of $0.06, compared to an anticipated loss of $0.60 per share [2][3] - The company's revenue for Q4 2024 reached $593.2 million, surpassing the expected $584 million, marking a 34.9% increase from $439.7 million in Q4 2023 [3][6] Financial Performance - Non-GAAP EPS for Q4 2024 was $0.06, significantly better than the consensus estimate of ($0.60) and an improvement from ($0.77) in Q4 2023 [3] - Total revenue was $593.2 million, exceeding the analysts' estimate of $584 million, and representing a 34.9% year-over-year increase [3] - Net product revenue reached $450.8 million, a 30.2% increase from $346.3 million in Q4 2023 [3][6] - The company reported a total net income (non-GAAP) of $8.0 million, a significant recovery from a loss of ($96.6 million) in the previous year [3] Product and Market Strategy - Alnylam focuses on RNA interference (RNAi) therapeutics, with a strong portfolio of approved products and a robust pipeline targeting rare diseases [4] - The company has successfully commercialized RNAi-based medicines like Onpattro and Amvuttra, contributing to its revenue growth [5] - The transthyretin-mediated amyloidosis franchise, including Onpattro and Amvuttra, generated $343 million in combined quarterly revenues, reflecting a 35% year-over-year improvement [6] Future Outlook - Management projects total net product revenues between $2.05 billion and $2.25 billion for 2025, driven by the anticipated approval and launch of Amvuttra for ATTR-CM [9] - Alnylam aims to expand its global market presence and pipeline, with over 25 programs expected to be in clinical stages by the end of 2025 [10]

Financial Data and Key Metrics Changes - In 2024, the company achieved combined net product revenues of over $1.646 billion, representing a 33% growth compared to 2023, and reached the upper end of the revised guidance range [8][44] - The company reported a non-GAAP operating income of $95 million for the full year, marking a significant milestone and a $156 million improvement compared to 2023 [8][47] - The gross margin on product sales was 81% for the full year, a 3% increase from 2023, primarily due to non-recurring prior year expenses [44][46] Business Line Data and Key Metrics Changes - The TTR franchise generated $343 million in global net product revenues in Q4 2024, a 35% increase compared to Q4 2023, driven by increased patient uptake [12][13] - The Rare franchise, including GIVLAARI and OXLUMO, delivered $108 million in combined product sales in Q4 2024, representing an 18% year-over-year growth [30][31] Market Data and Key Metrics Changes - In the U.S., the TTR franchise saw a 42% year-over-year increase in sales, driven by strong demand for AMVUTTRA and ONPATTRO [12][14] - Internationally, the TTR franchise grew 12% in Q4 compared to Q3 2024 and increased by 25% year-over-year [16] Company Strategy and Development Direction - The company aims to establish TTR leadership with vutrisiran potentially becoming a new standard of care in ATTR cardiomyopathy, supported by the advancement of next-generation TTR assets [9][10] - The strategy includes growth through innovation with a robust pipeline of clinical programs and a disciplined approach to capital allocation to sustain profitability [10][11] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism for 2025, highlighting it as a potential landmark year with expectations of continued growth driven by the TTR franchise and the upcoming launch of AMVUTTRA for ATTR cardiomyopathy [8][11] - The company is preparing for the regulatory decision on vutrisiran, with a PDUFA date set for March 23, 2025, and anticipates a ramp-up in demand post-approval [17][54] Other Important Information - The company ended 2024 with cash, cash equivalents, and marketable securities of $2.7 billion, an increase from $2.4 billion at the end of 2023 [48] - The company plans to host an R&D Day on February 25, 2025, to provide more comprehensive updates on its pipeline and development programs [41][54] Q&A Session Summary Question: How long will it take to establish payer policies after the approval of vutrisiran? - Management indicated that the formulary uptake will likely be meaningful in the second half of the year, with existing value-based agreements expected to facilitate this process [58][60] Question: Thoughts on AMVUTTRA's pricing and step edits for commercial insured patients? - Management expressed confidence in AMVUTTRA's product profile and anticipated smooth coverage from payers, similar to previous experiences with polyneuropathy [64][67] Question: Key factors impacting pricing adjustments for AMVUTTRA? - Management emphasized the importance of the product's value to patients and the ecosystem, with a J-code already in place to facilitate access [71][74] Question: Expectations for vutrisiran's potential revenue mix among naive patients versus switches from tafamidis? - Management expects a good mix of new patients and switches, positioning AMVUTTRA as a potential standard of care [96][98] Question: Competitive dynamics with Wainua in polyneuropathy? - Management noted strong growth in the TTR franchise despite competition, highlighting a differentiated product profile and continued market growth [102][105] Question: How will payer dynamics evolve in this category? - Management anticipates favorable coverage for AMVUTTRA, similar to previous experiences with polyneuropathy, and expects patient affordability to drive therapy adherence [115][118]

Company Performance - Alnylam Pharmaceuticals reported quarterly earnings of $0.06 per share, exceeding the Zacks Consensus Estimate of a loss of $0.21 per share, and showing improvement from a loss of $1.10 per share a year ago, resulting in an earnings surprise of 128.57% [1] - The company achieved revenues of $593.17 million for the quarter ended December 2024, surpassing the Zacks Consensus Estimate by 4.05%, compared to revenues of $439.72 million in the same quarter last year [2] - Over the last four quarters, Alnylam has surpassed consensus EPS estimates three times and has topped consensus revenue estimates three times as well [2] Stock Outlook - Alnylam shares have increased approximately 13% since the beginning of the year, outperforming the S&P 500's gain of 2.9% [3] - The current consensus EPS estimate for the upcoming quarter is -$0.52 on revenues of $523.19 million, while for the current fiscal year, the estimate is $0.41 on revenues of $2.51 billion [7] - The estimate revisions trend for Alnylam is currently favorable, leading to a Zacks Rank 2 (Buy) for the stock, indicating expected outperformance in the near future [6] Industry Context - Alnylam operates within the Medical - Biomedical and Genetics industry, which is currently ranked in the top 27% of over 250 Zacks industries, suggesting a favorable industry outlook [8] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can be tracked by investors [5]

Fourth Quarter and Full Year 2024 Financial Results February 13, 2025 © 2025 Alnylam Pharmaceuticals, Inc. 1 Agenda Welcome • Christine Lindenboom Chief Corporate Communications Officer Overview • Yvonne Greenstreet, MBChB, MBA Chief Executive Officer Commercial Highlights • Tolga Tanguler Chief Commercial Officer Pipeline • Pushkal Garg, M.D. Chief Medical Officer Financial Summary and Upcoming Milestones • Jeff Poulton Chief Financial Officer Q&A Session 2 Alnylam Forward Looking Statements This presentat ...