CAMBRIDGE, Mass.--(BUSINESS WIRE)--May 4, 2023--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today reported its consolidated financial results for the first quarter ended March 31, 2023 and reviewed recent business highlights.

“The first quarter of 2023 saw continued strong commercial execution, driven by the ongoing launch of AMVUTTRA, delivering robust 48% growth in total product sales compared with the first quarter 2022. We also made significant progress with our broad pipeline, delivering positive first-in-human results for an RNAi therapeutic in the CNS from an interim analysis of the Phase 1 study of ALN-APP in patients with early-onset Alzheimer’s disease. We believe this proof of concept is a significant catalyst for future potential growth for Alnylam with the expansion of our product engine to include tissues beyond the liver,” said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam. “We’re also excited for other key upcoming milestones from our pipeline, including topline Phase 2 results from the KARDIA-1 study of zilebesiran, which are expected mid-year. With this continued execution, we believe we are tracking well toward our Alnylam P⁵x25 goals of becoming a top-tier biotech company delivering sustained innovation and exceptional financial results.”

First Quarter 2023 and Recent Significant Corporate Highlights

Commercial Performance

Total TTR: ONPATTRO^® (patisiran) & AMVUTTRA^® (vutrisiran)

• Achieved global net product revenues for ONPATTRO and AMVUTTRA for the first quarter of $102 million and $102 million, respectively, representing 49% total TTR reported year-over-year growth compared to Q1 2022 and 54% growth on a CER* basis.
• Attained over 3,160 hATTR amyloidosis patients with polyneuropathy worldwide on commercial treatment with ONPATTRO or AMVUTTRA as of March 31, 2023.

Total Ultra-Rare: GIVLAARI^® (givosiran) & OXLUMO^® (lumasiran)

• Achieved global net product revenues for GIVLAARI and OXLUMO for the first quarter of $48 million and $24 million, respectively, representing 45% total Ultra-Rare reported year-over-year growth compared to Q1 2022 and 48% on a CER* basis.
• Attained over 550 patients worldwide on commercial GIVLAARI treatment as of March 31, 2023.
• Attained over 300 patients worldwide on commercial OXLUMO treatment as of March 31, 2023.

Leqvio^® (inclisiran)

• Launch in the U.S. and other markets is ongoing, with focus on patient on-boarding, removing access hurdles and enhancing medical education. In the U.S. Leqvio is covered at or near label for 76% of patients 14 months after launch. More than 50% of Leqvio source of business in the U.S. is now through “Buy and Bill” acquisition model.

R&D Highlights

Reported positive interim results from the ongoing single ascending dose (SAD) part of the Phase 1 study of ALN-APP in patients with early-onset Alzheimer’s disease (EOAD). These results establish the first human translation of Alnylam’s proprietary C16-siRNA conjugate platform for central nervous system (CNS) delivery and are the first clinical demonstration of gene silencing in the human brain using an RNAi therapeutic.

The Company announces today that it has submitted 18-month data from the APOLLO-B Phase 3 study to the U.S. FDA as part of the sNDA review for ONPATTRO (patisiran) for the treatment of the cardiomyopathy of ATTR amyloidosis.

Sanofi announced that results from the ATLAS-INH and ATLAS-A/B studies evaluating the efficacy and safety of fitusiran were published respectively in The Lancet and The Lancet Haematology, reinforcing the potential of investigational fitusiran to transform the current standard of care and address unmet needs for all types of hemophilia, regardless of inhibitor status.

Additional Key Pipeline Progress:

• Submitted an sNDA to the Brazilian Health Regulatory Agency (ANVISA) for ONPATTRO (patisiran) for the treatment of the cardiomyopathy of ATTR amyloidosis.
• Presented post-hoc analyses from the Phase 3 ENVISION study of givosiran in patients with AHP through Month 36 at the Hemostasis & Thrombosis Research Society (HTRS) Scientific Symposium.
• Presented preclinical data for ALN-HTT, for the potential treatment of Huntington’s disease, at the CHDI 18^th Annual Huntington’s Disease Therapeutics Conference, in collaboration with Regeneron.
• Announced today that dosing has been initiated in a Phase 1 study of ALN-KHK, for the potential treatment of type 2 diabetes.
• Regeneron announced that it has initiated a Phase 2 study of ALN-HSD in patients with NASH.
• Vir initiated the Phase 2 PREVAIL platform trial and its THRIVE/STRIVE sub-protocols evaluating combinations of ALN-HBV02 (VIR-2218) and VIR-3434 and/or PEG-IFN-α in two hepatitis B virus (HBV) patient populations, with the potential to evaluate other populations in the future. Initial data are expected in the first half of 2024.

Additional Business Updates

• Appointed Peter Kellogg to its Board of Directors.
• Published 2022 Corporate Responsibility Report.
• Named Fast Company Top Workplace for Innovators.
• Ranked #6 for gender diversity among executive leadership and #1 for gender diversity among board of directors in the Eos Foundation’s Women’s Power Gap study.

Upcoming Events

Alnylam announces today that it intends to present 18-month results from the APOLLO-B Phase 3 study of patisiran at ESC-HF 2023, being held May 20-23, 2023 in Prague.

Alnylam also announces today that it intends to present results from the Randomized Treatment Extension (RTE) of the HELIOS-A Phase 3 study evaluating a biannual dosing regimen of vutrisiran at the Italian Association for the Study of the Peripheral Nervous System (ASNP) conference, being held May 25-27, 2023 in Naples.

In addition, in early and mid-2023:

• Alnylam intends to report topline results from the KARDIA-1 Phase 2 study of zilebesiran.
  • Alnylam also intends to complete enrollment in the KARDIA-2 Phase 2 study of zilebesiran.
• Vir is conducting multiple trials evaluating the potential for ALN-HBV02 (VIR-2218) and VIR-3434 to achieve a functional cure for chronic HBV, which remain ongoing with readouts expected in 2023.
  • Vir also announced that the Phase 2 SOLSTICE trial evaluating ALN-HBV02 (VIR-2218) and VIR-232 as monotherapy and in combination for the treatment of people living with chronic hepatitis D virus, the most aggressive form of viral hepatitis, remains ongoing with data expected in the second half of 2023.

Financial Results for the Quarter Ended March 31, 2023

Net Product Revenues

• Net product revenues increased 48% at actual currency during the first quarter 2023, as compared to the prior year, and 52% at CER. The increase is primarily related to growth in our TTR product revenues driven by the launch of AMVUTTRA in the U.S. in the third quarter of 2022 as well as increased patients on GIVLAARI and OXLUMO therapies.

Net Revenues from Collaborations

• Net revenues from collaborations increased 41% during the first quarter 2023, as compared to the prior year, primarily due to an increase in revenue from our collaboration arrangements with Regeneron attributed to an increase in reimbursable activities under our research services arrangement in addition to an increase in revenue recognized associated with licensed programs within the collaboration.

Operating Expenses

Cost of Goods Sold

• Cost of goods sold as a percent of product sales increased during the first quarter 2023, as compared to the prior year, primarily due to increased royalties due to third parties driven by sales of AMVUTTRA partially offset by lower manufacturing costs for AMVUTTRA compared with ONPATTRO.

Research & Development (R&D) Expenses

• GAAP and non-GAAP R&D expenses increased during the first quarter 2023, as compared to the prior year, primarily due to increases in headcount to support our R&D pipeline, development expenses associated with the APOLLO-B (patisiran), HELIOS-B (vutrisiran), and KARDIA-1/KARDIA-2 (zilebesiran) clinical studies, and manufacturing related expenses associated with our pre-clinical activities.

Selling, General & Administrative (SG&A) Expenses

• GAAP and non-GAAP SG&A expenses increased during the first quarter 2023, as compared to the prior year, primarily due to increased headcount and other investments supporting our strategic growth, including the global launch of AMVUTTRA.

Other Financial Highlights

• Cash, cash equivalents and marketable securities were $2.07 billion as of March 31, 2023 compared to $2.19 billion as of December 31, 2022 with the decrease primarily due to our operating loss in the first quarter 2023.

The adjustments to the non-GAAP measures provided in the financial results above and in the financial guidance below are described under “Use of Non-GAAP Financial Measures” later in this press release. A reconciliation of our GAAP to non-GAAP results presented in this release is included in the tables at the end of this press release.

2023 Financial Guidance¹

Full year 2023 financial guidance is reiterated and consists of the following:

Use of Non-GAAP Financial Measures

This press release contains non-GAAP financial measures, including expenses adjusted to exclude certain non-cash expenses and certain losses outside the ordinary course of the Company’s business. These measures are not in accordance with, or an alternative to, GAAP, and may be different from non-GAAP financial measures used by other companies.

The items included in GAAP presentations but excluded for purposes of determining non-GAAP financial measures for the periods presented in this press release are stock-based compensation expenses and realized and unrealized losses on marketable equity securities. The Company has excluded the impact of stock-based compensation expense, which may fluctuate from period to period based on factors including the variability associated with performance-based grants for stock options and restricted stock units and changes in the Company’s stock price, which impacts the fair value of these awards. The Company has excluded the impact of the realized and unrealized losses on marketable equity securities because the Company does not believe these adjustments accurately reflect the performance of the Company’s ongoing operations for the period in which such gains or losses are reported, as their sole purpose is to adjust amounts on the balance sheet.

Percentage changes in revenue growth at CER, also a non-GAAP financial measure, are presented excluding the impact of changes in foreign currency exchange rates for investors to understand the underlying business performance. The current period’s foreign currency revenue values are converted into U.S. dollars using the average exchange rates from the prior period.

The Company believes the presentation of non-GAAP financial measures provides useful information to management and investors regarding the Company’s financial condition and results of operations. When GAAP financial measures are viewed in conjunction with non-GAAP financial measures, investors are provided with a more meaningful understanding of the Company’s ongoing operating performance and are better able to compare the Company’s performance between periods. In addition, these non-GAAP financial measures are among those indicators the Company uses as a basis for evaluating performance, allocating resources and planning and forecasting future periods. Non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between historical GAAP and non-GAAP measures presented in this release is provided later in this press release.

Conference Call Information

Management will provide an update on the Company and discuss first quarter 2023 results as well as expectations for the future via conference call on Thursday, May 4, 2023 at 8:30 am ET. To access the call, please register online at https://register.vevent.com/register/BId2c9a28af23d4f119b97d77675d085dc. Participants are requested to register at a minimum 15 minutes before the start of the call. A replay of the call will be available two hours after the call and archived on the same web page for six months.

A live audio webcast of the call will be available on the Investors section of the Company’s website at www.alnylam.com/events. An archived webcast will be available on the Alnylam website approximately two hours after the event.

About ONPATTRO^® (patisiran)

ONPATTRO is an RNAi therapeutic that is approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. ONPATTRO is also approved in the European Union, Switzerland and Brazil for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy, and in Japan for the treatment of hATTR amyloidosis with polyneuropathy. ONPATTRO is an intravenously administered RNAi therapeutic targeting transthyretin (TTR). It is designed to target and silence TTR messenger RNA, thereby reducing the production of TTR protein before it is made. Reducing the pathogenic protein leads to a reduction in amyloid deposits in tissues. For more information about ONPATTRO, including full Prescribing Information, visit ONPATTRO.com.

About AMVUTTRA^® (vutrisiran)

AMVUTTRA^® (vutrisiran) is an RNAi therapeutic approved in the United States for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. It is a double‑stranded small interfering RNA (siRNA) that targets mutant and wild‑type transthyretin (TTR) messenger RNA (mRNA). Using Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform, AMVUTTRA is designed for increased potency and high metabolic stability to allow for subcutaneous injection once every three months (quarterly). Results from the pivotal HELIOS-A Phase 3 study demonstrate AMVUTTRA rapidly reduces serum TTR levels, has the potential to reverse neuropathy impairment relative to baseline and improves other key measures of disease burden relative to external placebo in patients with the polyneuropathy of hATTR amyloidosis. For more information about AMVUTTRA, including the full U.S. Prescribing Information, visit AMVUTTRA.com.

About GIVLAARI^® (givosiran)

GIVLAARI (givosiran) is an RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) approved in the United States and Brazil for the treatment of adults with acute hepatic porphyria (AHP). GIVLAARI is also approved in the European Union for the treatment of AHP in adults and adolescents aged 12 years and older. In the pivotal study, givosiran was shown to significantly reduce the rate of porphyria attacks that required hospitalizations, urgent healthcare visits or intravenous hemin administration at home compared to placebo. GIVLAARI is Alnylam’s first commercially available therapeutic based on its Enhanced Stabilization Chemistry ESC-GalNAc conjugate technology to increase potency and durability. GIVLAARI is administered via subcutaneous injection once monthly at a dose based on actual body weight and should be administered by a healthcare professional. GIVLAARI works by specifically reducing elevated levels of ALAS1 messenger RNA (mRNA), leading to reduction of toxins associated with attacks and other disease manifestations of AHP. For more information about GIVLAARI, including the full U.S. Prescribing Information, visit GIVLAARI.com.

About OXLUMO^® (lumasiran)

OXLUMO (lumasiran) is an RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1). HAO1 encodes glycolate oxidase (GO). Thus, by silencing HAO1 and depleting the GO enzyme, OXLUMO inhibits production of oxalate – the metabolite that directly contributes to the pathophysiology of PH1. OXLUMO utilizes Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology, which enables subcutaneous dosing with increased potency and durability and a wide therapeutic index. OXLUMO has received regulatory approvals from the U.S. Food and Drug Administration (FDA) for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary and plasma oxalate levels in pediatric and adult patients and from the European Medicines Agency (EMA) for the treatment of PH1 in all age groups. In the pivotal ILLUMINATE-A study, OXLUMO was shown to significantly reduce levels of urinary oxalate relative to placebo, with the majority of patients reaching normal or near-normal levels. In the ILLUMINATE-B pediatric Phase 3 study, OXLUMO demonstrated an efficacy and safety profile consistent to that observed in ILLUMINATE-A. In the ILLUMINATE-C study, OXLUMO resulted in substantial reductions in plasma oxalate in patients with advanced PH1. Across all three studies, injection site reactions (ISRs) were the most common drug-related adverse reaction. OXLUMO is administered via subcutaneous injection once monthly for three months, then once quarterly beginning one month after the last loading dose at a dose based on actual body weight. For patients who weigh less than 10 kg, ongoing dosing remains monthly. OXLUMO should be administered by a healthcare professional. For more information about OXLUMO, including the full U.S. Prescribing Information, visit OXLUMO.com.

About LNP Technology

Alnylam has licenses to Arbutus Biopharma LNP intellectual property for use in RNAi therapeutic products using LNP technology.

About RNAi

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

About Alnylam Pharmaceuticals

Alnylam Pharmaceuticals (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding 20 years ago, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products are ONPATTRO^® (patisiran), AMVUTTRA^® (vutrisiran), GIVLAARI^® (givosiran), OXLUMO^® (lumasiran), and Leqvio^® (inclisiran), which is being developed and commercialized by Alnylam’s partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P⁵x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on Twitter at @Alnylam, on LinkedIn, or on Instagram.

Alnylam Forward Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations, beliefs, goals, plans or prospects including, without limitation, expectations regarding Alnylam’s aspiration to become a leading biotech company and the planned achievement of its “Alnylam P⁵x25” strategy, the potential for Alnylam to identify new potential drug development candidates and advance its research and development programs, Alnylam’s ability to obtain approval for new commercial products or additional indications for its existing products, and Alnylam’s projected commercial and financial performance, should be considered forward-looking statements. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or any future pandemic on Alnylam’s business, results of operations and financial condition; Alnylam’s ability to successfully execute on its “Alnylam P⁵x25” strategy; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates, including patisiran and vutrisiran; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, including patisiran and vutrisiran, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally; delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; delays or interruptions in the supply of resources needed to advance Alnylam’s research and development programs, including as may arise from the recent disruptions in the supply of non-human primates; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to successfully expand the indication for ONPATTRO or AMVUTTRA in the future; Alnylam's ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylam’s ability to maintain strategic business collaborations; Alnylam's dependence on third parties for the development and commercialization of certain products, including Novartis, Sanofi, Regeneron and Vir; the outcome of litigation; the potential impact of a current government investigation and the risk of future government investigations; and unexpected expenditures; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam's 2022 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q, and in its other SEC filings. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

This release discusses investigational RNAi therapeutics and uses of previously approved RNAi therapeutics in development and is not intended to convey conclusions about efficacy or safety as to those investigational therapeutics or uses. Patisiran has not been approved by any regulatory agency for the treatment of ATTR amyloidosis with cardiomyopathy. No conclusions can or should be drawn regarding its safety or effectiveness in treating cardiomyopathy in this population. There is no guarantee that any investigational therapeutics or expanded uses of commercial products will successfully complete clinical development or gain health authority approval.