What the changes say
- Alnylam achieved profitability in fiscal 2025, driven heavily by $2.99 billion in product revenues from AMVUTTRA, ONPATTRO, GIVLAARI, and OXLUMO.
- Commercial success is now heavily concentrated on AMVUTTRA following its March 2025 FDA approval for ATTR-CM.
- Risks reflect global expansion under the Alnylam 2030 strategy, alongside new generic challenges and pricing pressures from the IRA.
What changed since the prior 10-K
New
- NewRisks Related to Our Financial Results
If we are unable to sustain and grow revenues from sales of AMVUTTRA, our business would be materially harmed, our future operating results would be adversely impacted, and the market price of our common stock would likely decline
Our business heavily depends on sustaining and growing sales of AMVUTTRA, particularly following its March 2025 FDA approval for ATTR-CM.
- NewRisks Related to Our Financial Results
The marketing and sale of our approved products, including AMVUTTRA for ATTR amyloidosis with cardiomyopathy, or any future products for which we or our collaborators receive regulatory approval may be unsuccessful or less successful than anticipated
We face uncertainty in successfully executing our Alnylam 2030 strategy to market approved products like AMVUTTRA and advance RNAi delivery technologies.
- NewRisks Related to Our Financial Results
We have a history of losses and may not sustain profitability
Although we achieved profitability in fiscal 2025 with $2.99 billion in net product revenues, we carry an accumulated deficit of $6.70 billion and may not stay profitable.
- NewRisks Related to Our Financial Results
Although we sold a portion of the royalty stream from the global sales of Leqvio by Novartis, we are entitled to retain the remaining portions of the future royalties on Leqvio, and any negative developments related to Leqvio could have a material adverse effect on our receipt of those future royalties
If global Leqvio sales do not reach $1.00 billion by December 31, 2029, our retained royalty share from Blackstone Royalties drops from 50% to 45%.
- NewRisks Related to Managing Our Operations
We may have difficulty continuing to expand our global operations successfully at the scale necessary to support our Alnylam 2030 ambitions
Rapid workforce and operational growth under our Alnylam 2030 ambitions strain our infrastructure across the U.S., EU, Japan, and Latin America.
- NewRisks Related to Our Industry
If we are unable to achieve and maintain coverage and adequate reimbursement from third-party payors for AMVUTTRA or our other products, the commercial success of these products may be severely hindered
Commercial success for AMVUTTRA depends on securing timely coverage and adequate reimbursement from government and private third-party payors.
- NewRisks Related to Our Industry
If we fail to comply with broad and complex healthcare and other laws, we could face substantial penalties and our business, operations, and financial condition could be adversely affected
We are subject to strict federal and state healthcare laws, including the federal Anti-Kickback Statute, governing interactions with healthcare providers and payors.
- NewRisks Related to Our Industry
We are subject to U.S. and international privacy laws, including, for example, health privacy laws, comprehensive state privacy laws, consumer protection laws, data localization laws, and genetic privacy laws
We face complex U.S. and international privacy laws, FTC enforcement, and comprehensive state consumer privacy rules regarding health and genetic data.
- NewRisks Related to Patents, Licenses and Trade Secrets
Competitors could enter the market with generic versions of AMVUTTRA or our or our collaborators’ other marketed products developed in collaboration with us, which may result in a material decline in sales of affected product(s)
Competitors may file ANDAs or 505(b)(2) applications seeking approval for generic versions of AMVUTTRA or other marketed products under the Hatch-Waxman Act.
- NewRisks Related to Patents, Licenses and Trade Secrets
certification must be given to the innovator, and if within 45 days of receiving notice the innovator sues to enforce its patents, approval of the ANDA is stayed for 30 months, or as lengthened or shortened by the court
Our collaborator Novartis received a Paragraph IV certification notice for Leqvio in January 2026, risking patent litigation we cannot directly control.
- NewRisks Related to Our Convertible Notes
Because the 2028 Notes will not bear regular interest, holders may not earn a return on their investment in the 2028 Notes
Our 2028 Notes do not bear regular interest, meaning holders may earn no return unless the common stock price exceeds the conversion price.
Dropped
- DroppedRisks Related to Our Financial Results
The marketing and sale of our approved products or any future products may be unsuccessful or less successful than anticipated, and we may be unable to expand the approved indications for certain of our commercial products, including AMVUTTRA
- DroppedRisks Related to Our Financial Results
We have a history of losses and may not become and remain profitable
- DroppedRisks Related to Our Financial Results
a result, any factor that has an adverse impact on sales of Leqvio could affect our ability to meet the $1.00 billion repayment threshold in this timeframe, which in turn would have a negative impact on the percentage of the Leqvio royalty stream that we are entitled to retain
Uncertainty in marketing approved products and expanding approved indications for AMVUTTRA.
- DroppedRisks Related to Our Financial Results
Any future outbreaks of pandemics or public health emergencies, may directly or indirectly adversely affect our business, results of operations and financial condition
History of losses and uncertainty in achieving profitability with an accumulated deficit of $7.29 billion.
- DroppedRisks Related to Managing Our Operations
We may have difficulty expanding our operations successfully as we continue our evolution from a U.S.- and EU-based company primarily involved in discovery, preclinical testing and clinical development into a global company that develops and commercializes multiple products in multiple geographies
- DroppedRisks Related to Our Industry
regulatory authorities could have a material adverse effect on our or our collaborators’ efforts to obtain regulatory approval for our or our collaborators’ product candidates, which could have a material adverse effect on our business, prospects, operating results or financial condition
Factors impacting Leqvio sales and the $1.00 billion repayment threshold for Blackstone Royalties.
- DroppedRisks Related to Our Industry
used in the calculation of reimbursement and/or discounts on approved products; and to pay rebates or offer discounts on pharmaceutical products
- DroppedRisks Related to Our Industry
Moreover, federal, state and foreign laws or regulations are subject to change, and while we, our collaborators, CMOs and/or service providers currently may be compliant, we could fall out of compliance due to changes in interpretation, prevailing industry standards or the legal structure
- DroppedRisks Related to Our Industry
Our ability to obtain services, reimbursement or funding from the federal government may be impacted by possible reductions in federal spending and services, and any inability on our part to effectively adapt to such changes could substantially affect our business, prospects, operating results and financial condition
- DroppedRisks Related to Patents, Licenses and Trade Secrets
favor of each party on certain TAF associated claims and awarded Ionis compensation of $41.2 million for a TAF on certain rights we received in the Sanofi restructuring
- DroppedRisks Related to Competition
continue to have a competitive product profile for the treatment of patients with hATTR amyloidosis with polyneuropathy, it is possible that ONPATTRO and/or AMVUTTRA may not compete favorably with these products and product candidates, or others, and, as a result, may not achieve commercial success
- DroppedRisks Related to Our Common Stock
We expect that results from our and our collaborators’ clinical development activities and the clinical development activities of our competitors will continue to be released periodically and may result in significant volatility in the price of our common stock
Potential disruptions from future pandemics or public health emergencies.
- DroppedRisks Related to Our Convertible Notes
convert their notes, we may settle our conversion obligation by delivering to them a significant number of shares of our common stock, which would cause dilution to our existing stockholders
Reworded
- 91% rewrittenRisks Related to Our Industry
We believe that the efforts of governments and third-party payors to contain or reduce the cost of healthcare and broaden the availability of healthcare will continue to affect the business and financial condition of pharmaceutical and biopharmaceutical companies
Added specific references to the Inflation Reduction Act of 2022, Medicare Parts B and D reforms, price inflation rebates, and out-of-pocket caps.
Was: We believe that the efforts of governments and third-party payors to contain or reduce the cost of healthcare and legislative and regulatory proposals to broaden the availability of healthcare will continue to affect the business and financial condition of pharmaceutical and biopharmaceutical companies
- 83% rewritten
Business Related Risks – Risks Related to Our Financial Results
Updated financial risk headings to emphasize reliance on AMVUTTRA revenue growth and sustaining profitability following 2025 financial results.
- 78% rewrittenRisks Related to Our Industry
We or our collaborators may be unable to obtain U.S. or foreign regulatory approval for our or our product candidates and, as a result, we or our collaborators may be unable to commercialize such product candidates
Maintained regulatory approval risk text while re-ordering and grouping with updated commercial strategy sections.
Was: We or our collaborators may be unable to obtain U.S. or foreign regulatory approval for our or our collaborated product candidates and, as a result, we or our collaborators may be unable to commercialize such product candidates
- 77% rewrittenRisks Related to Competition
The pharmaceutical market is intensely competitive. If we or our collaborators are unable to compete effectively with existing drugs, new treatment methods and new technologies, we or our collaborators may be unable to commercialize successfully any drugs that we or our collaborators develop
Refined the competitive landscape description for pharmaceutical and biotechnology market rivals.
- 69% rewrittenRisks Related to Patents, Licenses and Trade Secrets
Other companies or organizations may challenge our patent rights or may assert patent rights that prevent us from developing and commercializing our products
Adjusted RNAi patent landscape framing by removing reference to it being a 'relatively new' scientific field.
- 65% rewrittenRisks Related to Our Industry
Governments outside the U.S. may impose strict price controls or have significant market leverage to negotiate discounted prices, which may adversely affect our revenues
Clarified foreign pricing controls and cost-effectiveness trial requirements outside the U.S.
Was: Governments outside the U.S. may impose strict price controls, which may adversely affect our revenues
- 64% rewrittenRisks Related to Our Convertible Notes
Transactions relating to the Notes may affect the value of our common stock
Added details regarding Capped Calls entered into with option counterparties in connection with the issuance of the Notes.
- 57% rewrittenRisks Related to Our Financial Results
Volatility in foreign currency exchange rates could have a material adverse effect on our operating results
Specified that foreign exchange risk stems from expenses and liabilities required to be paid in currencies other than the U.S. dollar.
- 54% rewrittenRisks Related to Our Industry
Even if we or our collaborators receive regulatory approval to market our product candidates, the market may not be receptive to our product candidates upon their commercial introduction, which could adversely affect our business, prospects, operating results and financial condition
- 45% rewrittenRisks Related to Our Industry
Any products we currently market or may develop in the future may become subject to unfavorable pricing regulations or healthcare reform initiatives, thereby harming our business, prospects, operating results and financial condition
Was: Any products we currently market or may develop in the future may become subject to unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, thereby harming our business, prospects, operating results and financial condition
- 43% rewrittenRisks Related to Patents, Licenses and Trade Secrets
If we fail to comply with our obligations under any licenses or related agreements, we may be required to pay damages and could lose license or other rights that are necessary for developing, commercializing and protecting our RNAi technology, as well as our products and product candidates
- 41% rewrittenRisks Related to Our Industry
If we are unable to continue to develop and scale our own global marketing, sales, market access and distribution capabilities for our current and any future products, we will not be able to successfully commercialize our products without reliance on third parties
- 35% rewrittenRisks Related to Our Industry
Any of the above occurrences could reduce or eliminate sales of our approved products, increase our expenses and impair our ability to successfully commercialize one or more of these products
- 33% rewrittenRisks Related to Our Financial Results
If the estimates we make, or the assumptions on which we rely, in preparing our financial statements and/or our projected guidance prove inaccurate, our actual results may vary from those reflected in our projections and accruals
- 32% rewrittenRisks Related to Our Dependence on Third Parties
If any collaborator materially amends, terminates or fails to perform its obligations under agreements with us, the development and commercialization of our products or product candidates could be delayed or terminated
Was: If any collaborator materially amends, terminates or fails to perform its obligations under agreements with us, the development and commercialization of our product candidates could be delayed or terminated
- 30% rewrittenRisks Related to Our Financial Results
We will require substantial funds to continue our research, development and commercialization activities, and if we require greater funds than we have estimated, we may need to critically limit, significantly scale back or cease certain activities
- 27% rewrittenRisks Related to Our Dependence on Third Parties
If any of these occur, the development and commercialization of one or more products or product candidates could be delayed, curtailed or terminated because we may not have sufficient financial resources or capabilities to continue such development and commercialization on our own
- 24% rewrittenRisks Related to Our Common Stock
Our stock price has been and may in the future be volatile, and an investment in our common stock could suffer a decline in value
- 23% rewrittenRisks Related to Patents, Licenses and Trade Secrets
If we are not able to obtain and enforce patent protection for our discoveries, our ability to develop and commercialize our product candidates will be harmed
- 23% rewrittenRisks Related to Our Convertible Notes
We may not have sufficient cash flow from our business to pay our indebtedness
- 22% rewrittenRisks Related to Our Industry
Our employees may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements or insider trading violations, which could significantly harm our business, prospects, operating results and financial condition
All 54 risk factors
Headings as the filing states them, in filing order.
Other
- 01SUMMARY OF MATERIAL RISKS ASSOCIATED WITH OUR BUSINESS
- 02Business Related Risks – Risks Related to Our Financial Results83% rewritten
Risks Related to Our Financial Results
- 03If we are unable to sustain and grow revenues from sales of AMVUTTRA, our business would be materially harmed, our future operating results would be adversely impacted, and the market price of our common stock would likely declineNew
- 04The marketing and sale of our approved products, including AMVUTTRA for ATTR amyloidosis with cardiomyopathy, or any future products for which we or our collaborators receive regulatory approval may be unsuccessful or less successful than anticipatedNew
- 05We have a history of losses and may not sustain profitabilityNew
- 06We will require substantial funds to continue our research, development and commercialization activities, and if we require greater funds than we have estimated, we may need to critically limit, significantly scale back or cease certain activities30% rewritten
- 07Although we sold a portion of the royalty stream from the global sales of Leqvio by Novartis, we are entitled to retain the remaining portions of the future royalties on Leqvio, and any negative developments related to Leqvio could have a material adverse effect on our receipt of those future royaltiesNew
- 08If the estimates we make, or the assumptions on which we rely, in preparing our financial statements and/or our projected guidance prove inaccurate, our actual results may vary from those reflected in our projections and accruals33% rewritten
- 09The investment of our cash, cash equivalents and marketable securities is subject to risks which may cause losses and affect the liquidity of these investments
- 10Volatility in foreign currency exchange rates could have a material adverse effect on our operating results57% rewritten
- 11Changes in tax laws could adversely affect our business, prospects, operating results and financial condition
- 12We may incur additional tax liabilities related to our operations
Risks Related to Our Dependence on Third Parties
- 13If any collaborator materially amends, terminates or fails to perform its obligations under agreements with us, the development and commercialization of our products or product candidates could be delayed or terminated32% rewritten
- 14If any of these occur, the development and commercialization of one or more products or product candidates could be delayed, curtailed or terminated because we may not have sufficient financial resources or capabilities to continue such development and commercialization on our own27% rewritten
- 15We rely on third parties to conduct our clinical trials, and if such third parties fail to fulfill their obligations, our development plans may be adversely affected
Risks Related to Managing Our Operations
- 16If we are unable to attract and retain qualified key management and scientists, development, medical and commercial staff, consultants and advisors, our ability to implement our business plan may be adversely affected
- 17We may have difficulty continuing to expand our global operations successfully at the scale necessary to support our Alnylam 2030 ambitionsNew
- 18The use of social media presents risks and challenges
- 19Our business and operations could suffer in the event of system failures or unauthorized or inappropriate use of or access to our systems
Risks Related to Our Industry
- 20Any product candidate we or our collaborators develop may fail in development or experience significant delays
- 21Difficulty in enrolling patients could delay or prevent clinical trials of our product candidates, and ultimately delay or prevent regulatory approval
- 22We or our collaborators may be unable to obtain U.S. or foreign regulatory approval for our or our product candidates and, as a result, we or our collaborators may be unable to commercialize such product candidates78% rewritten
- 23Any of the above occurrences could reduce or eliminate sales of our approved products, increase our expenses and impair our ability to successfully commercialize one or more of these products35% rewritten
- 24We may incur significant liability if enforcement authorities allege or determine that we are engaging in commercial activities with respect to our unapproved product candidates or promoting our commercially approved products in a way that violates applicable regulations
- 25Even if we or our collaborators receive regulatory approval to market our product candidates, the market may not be receptive to our product candidates upon their commercial introduction, which could adversely affect our business, prospects, operating results and financial condition54% rewritten
- 26If we are unable to continue to develop and scale our own global marketing, sales, market access and distribution capabilities for our current and any future products, we will not be able to successfully commercialize our products without reliance on third parties41% rewritten
- 27Any products we currently market or may develop in the future may become subject to unfavorable pricing regulations or healthcare reform initiatives, thereby harming our business, prospects, operating results and financial condition45% rewritten
- 28We believe that the efforts of governments and third-party payors to contain or reduce the cost of healthcare and broaden the availability of healthcare will continue to affect the business and financial condition of pharmaceutical and biopharmaceutical companies91% rewritten
- 29If we are unable to achieve and maintain coverage and adequate reimbursement from third-party payors for AMVUTTRA or our other products, the commercial success of these products may be severely hinderedNew
- 30Governments outside the U.S. may impose strict price controls or have significant market leverage to negotiate discounted prices, which may adversely affect our revenues65% rewritten
- 31If we fail to comply with broad and complex healthcare and other laws, we could face substantial penalties and our business, operations, and financial condition could be adversely affectedNew
- 32We are subject to U.S. and international privacy laws, including, for example, health privacy laws, comprehensive state privacy laws, consumer protection laws, data localization laws, and genetic privacy lawsNew
- 33There is a substantial risk of product liability claims in our business. If we are unable to obtain sufficient insurance, a product liability claim against us could adversely affect our business, prospects, operating results and financial condition
- 34Our employees may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements or insider trading violations, which could significantly harm our business, prospects, operating results and financial condition22% rewritten
- 35If we do not comply with laws regulating the protection of the environment and health and human safety, our business, prospects, operating results and financial condition could be adversely affected
Risks Related to Patents, Licenses and Trade Secrets
- 36If we are not able to obtain and enforce patent protection for our discoveries, our ability to develop and commercialize our product candidates will be harmed23% rewritten
- 37We license patent rights from third-party owners. If such owners do not properly or successfully obtain, maintain or enforce the patents underlying such licenses, our competitive position and business, prospects, operating results and financial condition may be harmed
- 38Other companies or organizations may challenge our patent rights or may assert patent rights that prevent us from developing and commercializing our products69% rewritten
- 39Competitors could enter the market with generic versions of AMVUTTRA or our or our collaborators’ other marketed products developed in collaboration with us, which may result in a material decline in sales of affected product(s)New
- 40certification must be given to the innovator, and if within 45 days of receiving notice the innovator sues to enforce its patents, approval of the ANDA is stayed for 30 months, or as lengthened or shortened by the courtNew
- 41If we fail to comply with our obligations under any licenses or related agreements, we may be required to pay damages and could lose license or other rights that are necessary for developing, commercializing and protecting our RNAi technology, as well as our products and product candidates43% rewritten
- 42Confidentiality agreements with employees and others may not adequately prevent disclosure of trade secrets and other proprietary information
Risks Related to Competition
- 43The pharmaceutical market is intensely competitive. If we or our collaborators are unable to compete effectively with existing drugs, new treatment methods and new technologies, we or our collaborators may be unable to commercialize successfully any drugs that we or our collaborators develop77% rewritten
Risks Related to Our Common Stock
- 44Our stock price has been and may in the future be volatile, and an investment in our common stock could suffer a decline in value24% rewritten
- 45Sales of a substantial number of shares of our common stock, including by us, our officers or directors, or our significant stockholders, into the public market could cause the price of our common stock to decline
- 46Anti-takeover provisions in our governing documents and under Delaware law could make an acquisition of us, which may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management or members of our board of directors
Risks Related to Our Convertible Notes
- 47We may not have sufficient cash flow from our business to pay our indebtedness23% rewritten
- 48We may not have the ability to raise the funds necessary to settle for cash conversions of the Notes or to repurchase the Notes for cash upon a fundamental change
- 49The conditional conversion feature of the Notes, if triggered, may adversely affect our liquidity
- 50Transactions relating to the Notes may affect the value of our common stock64% rewritten
- 51In connection with establishing their initial hedges of the Capped Calls, the Option Counterparties or their respective affiliates entered into various derivative transactions with respect to our common stock and/or purchased shares of our common stock concurrently with or shortly after the pricing of the Notes
- 52We are subject to counterparty risk with respect to the Capped Calls
- 53Because the 2028 Notes will not bear regular interest, holders may not earn a return on their investment in the 2028 NotesNew
- 54The accounting method for reflecting the Notes on our consolidated balance sheet, accruing interest expense for the Notes and reflecting the underlying shares of our common stock in our reported diluted earnings per share may adversely affect our reported earnings and financial condition
Other Alnylam Pharmaceuticals 10-Ks
- FY2024 10-K risk factors56 risks
Alnylam faces substantial financial risks with an accumulated deficit of $7.29 billion as of December 31, 2024. The company relies heavily on commercial success for AMVUTTRA and royalties from Leqvio. Operations depend on third-party manufacturing, clinical trial execution, and complex global intellectual property licensing. Regulatory pricing pressures and compliance across international jurisdictions present ongoing challenges.
Filed Feb 13, 2025
About this page
The headings are the filing's own. The one-line readings and the overview are automated and can be wrong: read Item 1A of the 10-K for the exact wording.