The Company's Beginnings and Early Achievements Alnylam was founded in 2002 with the goal of translating the discovery of RNAi into a new generation of therapeutics. In its early years, the company focused on establishing a strong intellectual property position in the RNAi field and forging strategic collaborations with leading pharmaceutical and biotechnology companies. Alnylam devoted substantial efforts to business planning, research, development, manufacturing and commercial efforts, acquiring and expanding intellectual property rights, recruiting management and technical staff, and raising capital.
The company faced numerous challenges in translating the scientific discovery of RNAi into viable therapeutic products, including developing effective delivery methods to target specific tissues and cells. Despite these obstacles, Alnylam persevered, leveraging its collaborative approach to advance its research and development efforts.
A major milestone was achieved in 2018 with the FDA approval of ONPATTRO, Alnylam's first commercially approved RNAi therapeutic, for the treatment of polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. This approval marked a significant achievement, as ONPATTRO was the first-ever FDA-approved RNAi therapeutic. Following this success, Alnylam received approvals for AMVUTTRA in 2022, GIVLAARI in 2019, and OXLUMO in 2020, further establishing the company as a leader in the development and commercialization of RNAi therapeutics.
The Expansion of Alnylam's Commercial Portfolio The approval of ONPATTRO was a significant milestone for Alnylam, marking the company's transition from a pure-play research and development organization to a global commercial-stage biopharmaceutical company. Building on this success, Alnylam has since expanded its commercial portfolio, receiving approvals for AMVUTTRA, GIVLAARI, and OXLUMO, all of which are first-in-class RNAi therapeutics targeting rare and devastating diseases.
In 2024, Alnylam reported impressive financial results, with global net product revenues reaching $1.646 billion, representing a 33% increase compared to the previous year. This growth was driven by the continued strong performance of the company's TTR franchise, which includes ONPATTRO and AMVUTTRA, as well as its rare disease portfolio, encompassing GIVLAARI and OXLUMO.
Alnylam's TTR Franchise: Establishing a New Standard of Care Alnylam's TTR franchise has been a key driver of the company's success, with ONPATTRO and AMVUTTRA offering transformative treatments for patients with hATTR amyloidosis. In 2024, the TTR franchise generated $705 million in revenue in the U.S. alone, reflecting a 39% year-over-year growth.
ONPATTRO, an intravenously administered RNAi therapeutic targeting TTR, was first approved in the U.S. in 2018 for the treatment of the polyneuropathy of hereditary TTR (hATTR) amyloidosis in adults. It has since received approvals in the European Union, Japan, and several other countries. In February 2025, ONPATTRO received regulatory approval from the Brazilian Health Regulatory Agency for the treatment of ATTR amyloidosis with cardiomyopathy, further expanding its global reach.
AMVUTTRA, a subcutaneously administered RNAi therapeutic targeting TTR, was first approved in the U.S. in 2022 for the treatment of hATTR amyloidosis with polyneuropathy in adults. It has also been approved in the EU, UK, Japan, and several other countries for the treatment of hATTR amyloidosis.
The recent positive results from the HELIOS-B Phase 3 clinical trial of AMVUTTRA (vutrisiran) in patients with ATTR amyloidosis with cardiomyopathy have further bolstered Alnylam's position in the TTR market. These data demonstrated a statistically significant reduction in the composite of all-cause mortality and recurrent cardiovascular events, as well as improvements in key measures of disease progression, such as functional capacity and quality of life. Based on these compelling results, Alnylam has filed for regulatory approvals of AMVUTTRA for the treatment of ATTR amyloidosis with cardiomyopathy in the U.S., Europe, and other key markets.
For the full year 2024, Alnylam reported net product revenues of $252.9 million for ONPATTRO and $970.5 million for AMVUTTRA, highlighting the strong patient demand for these transformative therapies.
The company's commitment to innovation in the TTR space extends beyond AMVUTTRA, with the development of Nucresiran (formerly ALN-TTRsc04), a next-generation TTR silencer that has the potential to offer even greater durability and convenience for patients. Nucresiran has recently received orphan drug designation from the FDA for the treatment of ATTR amyloidosis, and Alnylam plans to initiate a Phase 3 clinical trial in ATTR amyloidosis with cardiomyopathy in the first half of 2025.
Diversifying the Pipeline and Driving Sustainable Innovation While Alnylam's TTR franchise has been a cornerstone of the company's success, the diversification of its pipeline has been a key strategic focus. The company has leveraged its RNAi platform to advance numerous investigational therapies across a broad range of disease areas, including cardiovascular, neuroscience, and metabolic disorders, among others.
Notable pipeline programs include Zilebesiran, an investigational RNAi therapeutic targeting angiotensinogen for the treatment of hypertension, and Mivelsiran, an RNAi therapeutic in development for the treatment of Alzheimer's disease and cerebral amyloid angiopathy. Alnylam has also initiated several new Phase 1 programs in 2024, including for Huntington's disease, bleeding disorders, and type 2 diabetes, further demonstrating the breadth and depth of its R&D efforts.
The company's commitment to innovation extends beyond its pipeline, as Alnylam continues to enhance its RNAi platform, including advancements in delivery technologies, such as the IKARIA platform, which has the potential to enable robust target knockdown with infrequent dosing regimens. These platform innovations, combined with the company's focus on genetically validated targets, position Alnylam for sustainable long-term growth and the ability to address a wide range of unmet medical needs.
Financials and Liquidity Alnylam's strong commercial execution, coupled with its diversified pipeline, has positioned the company for financial success. In 2024, the company reported non-GAAP operating income of $95 million, a significant milestone in its journey towards sustained profitability.
For the fourth quarter of 2024, Alnylam reported revenue of $593.17 million, representing a robust year-over-year growth of 34.9%. However, the company recorded a net loss of $83.76 million for the quarter, highlighting the ongoing investments in research and development and commercialization efforts.
Alnylam maintains a strong liquidity position, with a current ratio of 2.78 and a quick ratio of 2.71, indicating the company's ability to meet its short-term obligations. This financial stability provides Alnylam with the flexibility to continue investing in its pipeline and commercial infrastructure.
Looking ahead to 2025, Alnylam has provided robust financial guidance, projecting combined net product sales in the range of $2.05 billion to $2.25 billion, representing growth of 31% at the midpoint compared to 2024. This guidance is primarily driven by the anticipated launch of AMVUTTRA for the treatment of ATTR amyloidosis with cardiomyopathy, as well as continued growth in the company's TTR and rare disease franchises.
Specifically, Alnylam expects total TTR franchise sales to reach $1.6 billion to $1.725 billion in 2025, representing full year growth of 36% at the midpoint. This guidance assumes approval and launch of AMVUTTRA for ATTR cardiomyopathy in the U.S. by the PDUFA date of March 23, 2025, as well as launches in Germany and Japan in the second half of 2025.
The company's rare disease franchise, which includes GIVLAARI and OXLUMO, is projected to generate sales of $450 million to $525 million in 2025, representing full year growth of 15% at the midpoint. In 2024, GIVLAARI and OXLUMO reported net product revenues of $255.9 million and $167.1 million, respectively, demonstrating the success of these treatments in addressing rare and serious diseases with high unmet medical needs.
Furthermore, Alnylam anticipates collaboration and royalty revenue of $650 million to $750 million in 2025, representing 16% growth at the midpoint. This includes royalties from Leqvio, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia, which is being developed and commercialized by Alnylam's collaborator Novartis. Leqvio has received marketing authorization in the U.S., EU, China, Japan, and over 100 countries globally, marking an important milestone as Alnylam's first RNAi therapeutic approved for a prevalent disease.
Alnylam expects combined non-GAAP R&D and SG&A expenses to be in the range of $2.1 billion to $2.2 billion in 2025, with the midpoint representing 17% growth compared to 2024. Despite these increased investments, the company anticipates delivering non-GAAP operating income profitability in 2025, a testament to Alnylam's disciplined financial management and its ability to translate its scientific and commercial successes into sustainable financial performance.
Navigating Challenges and Positioning for the Future Throughout its journey, Alnylam has faced and overcome various challenges, including regulatory hurdles, competitive pressures, and the impact of global events, such as the COVID-19 pandemic. The company's ability to navigate these obstacles and maintain its momentum is a testament to its resilience and the strength of its leadership team.
As Alnylam continues to execute on its Alnylam P5x25 strategy, the company is well-positioned to solidify its position as a top-tier biotech company. This strategy aims to transform Alnylam into a leading biotech by the end of 2025 through the delivery of innovative medicines, exceptional financial performance, and sustainable growth.
With a robust pipeline, a growing commercial portfolio, and a strong financial foundation, Alnylam is poised to deliver transformative therapies to patients around the world, while driving sustainable value creation for its shareholders. The company's diversified portfolio of approved products and promising pipeline candidates across a broad range of disease areas, including cardiometabolic diseases, complement-mediated diseases, Alzheimer's disease, and Huntington's disease, position it for continued commercial and financial success in the coming years.
Conclusion Alnylam Pharmaceuticals' journey from a pioneering RNAi research company to a global commercial-stage biopharmaceutical leader is a testament to the company's relentless pursuit of innovation and its unwavering commitment to transforming the lives of patients. With a diversified pipeline, a strong commercial presence, and a clear path to profitability, Alnylam is well-equipped to capitalize on the vast opportunities ahead and continue its trajectory of sustainable growth and value creation. As the company advances towards its goal of becoming a top-tier biotech by the end of 2025, investors and patients alike can look forward to the potential impact of Alnylam's groundbreaking RNAi therapeutics in addressing a wide range of unmet medical needs.