Alnylam Pharmaceuticals Reports Third Quarter 2018 Financial Results and Highlights Recent Period Activity
− Obtained FDA and EMA Approvals of ONPATTRO™ (patisiran) – the First-Ever RNAi Therapeutic – and Launched in U.S. and EU −
− Received 125 U.S. Patient Start Forms in First Seven Weeks of ONPATTRO Launch −
− Reported Positive Topline Interim Analysis Results from ENVISION Phase 3 Study of Givosiran in Patients with Acute Hepatic Porphyrias −
− Advanced Lumasiran into ILLUMINATE Phase 3 Program −
− Maintained Strong Balance Sheet with
“The third quarter and recent period were truly revolutionary for
Alnylam with the approval of ONPATTRO in both the U.S. and EU, heralding
the arrival of RNAi therapeutics as a whole new class of medicines. With
these approvals and the subsequent launches, we have begun to realize
the promise of RNAi therapeutics on a global scale,” said
“With the approval and launch of ONPATTRO, Alnylam is now a global
commercial-stage company. With only seven weeks of results for the third
quarter, we’re encouraged by the number of U.S. patient start forms, and
emerging prescriber base, highlighting what we believe is strong demand
for ONPATTRO for adults with polyneuropathy caused by hATTR amyloidosis.
Moreover, we believe our regional presence in
Third Quarter 2018 and Recent Period Significant Corporate Highlights
Launched ONPATTRO™ (patisiran) in the U.S. and EU, initially in
Received 125 U.S. patient Start Forms as of
September 30, 2018.
Recognized ONPATTRO revenue of
$0.5 millionfor the quarter ended September 30, 2018.
- Announced alignment on value-based agreements with leading health insurers and launched Alnylam Assist™, a comprehensive patient support services program for ONPATTRO in the U.S.
Achieved the first-ever regulatory approval of an RNAi therapeutic,
ONPATTRO (patisiran), in the U.S. and EU.
Received U.S. Food and Drug Administration( FDA) approval of ONPATTRO for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults.
Received marketing authorization from the
European Commission for ONPATTROfor the treatment of hATTR amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy.
Continued global efforts to bring ONPATTRO to patients with
submission of a New Drug Application to Japan’s Pharmaceuticals
Medical Devices Agencyand receipt of a Priority Review designation in Canada.
Published results from the APOLLO Phase 3 study of
patisiran in the
July 5, 2018issue of The New England Journal of Medicineand APOLLO exploratory cardiac endpoint data in the September 14, 2018issue of Circulation.
Advanced ALN-TTRsc02, a subcutaneously administered investigational
RNAi therapeutic in development for the treatment of ATTR amyloidosis.
Aligned the design of HELIOS-A, a pivotal Phase 3 study of
ALN-TTRsc02 in patients with hATTR amyloidosis polyneuropathy,
FDAand European Medicines Agency(EMA) feedback.
- The Company is on track to start the HELIOS-A study in late 2018 and plans to initiate additional Phase 3 studies of ALN-TTRsc02, including in hereditary and wild-type ATTR amyloidosis cardiomyopathy, in 2019.
- Aligned the design of HELIOS-A, a pivotal Phase 3 study of ALN-TTRsc02 in patients with hATTR amyloidosis polyneuropathy, with
Advanced givosiran, an investigational RNAi therapeutic in development
for the treatment of acute hepatic porphyrias (AHPs).
- Announced positive topline results from the interim analysis of the ENVISION Phase 3 study of givosiran.
- Announced plans to initiate a rolling submission of a New Drug Application (NDA) and pursue full approval based on complete results – now expected in early 2019 – from the ENVISION Phase 3 study. The rolling NDA submission is expected to be initiated in 2018, with full clinical sections submitted in mid-2019, assuming positive results.
Advanced lumasiran, an investigational RNAi therapeutic in development
for the treatment of primary hyperoxaluria type 1 (PH1).
- Announced initiation of ILLUMINATE-A, a global Phase 3 pivotal trial of lumasiran in children and adults with PH1. Alnylam expects to report topline results from ILLUMINATE-A in late 2019 and, if positive, submit filings for global regulatory approvals starting in early 2020.
Presented updated positive results from the Phase 1/2 study in PH1
patients at the 2018
European Society for Paediatric Nephrologyand the American Society of Nephrologyannual meetings.
Announced alignment with the
FDAon the trial design for ILLUMINATE-B, a Phase 3 study of lumasiran in PH1 patients less than six years of age with preserved renal function.
- Expanded the Alnylam Act® program to include no-charge, third-party genetic testing and counseling for adults and children who may carry a mutation in the gene encoding alanine-glyoxylate aminotransferase (AGXT), which is associated with PH1.
Alnylam’s partner, The
Medicines Company, announced in October that the Independent Data Monitoring Committee for the ongoing inclisiran Phase 3 clinical trials (ORION 9, 10, and 11) conducted its fourth planned review of safety and efficacy data from the ORION trials and recommended that the trials continue without modification.
- The safety database for inclisiran now provides 1,899 years of patient exposure to an RNAi therapeutic, representing the industry’s most comprehensive body of safety data for an RNAi therapeutic.
Sanofi, continues enrollment in the fitusiran Phase 3 ATLAS program in patients with hemophilia A or B with and without inhibitors.
Advanced early-stage RNAi pipeline.
- Submitted a Clinical Trial Authorization (CTA) application for ALN-AAT02, an investigational RNAi therapeutic for the treatment of alpha-1 antitrypsin deficiency-associated liver disease (alpha-1 liver disease), which is based on Alnylam’s Enhanced Stabilization Chemistry-Plus (ESC+) GalNAc conjugate technology.
- The Company announces today that due to recruitment challenges, it has discontinued a Phase 2 study of cemdisiran in atypical hemolytic uremic syndrome (aHUS). Alnylam will now focus its cemdisiran clinical efforts on a Phase 2 study in IgA nephropathy.
platform innovations at the
Oligonucleotide Therapeutics Society2018 Annual Meeting, including pre-clinical results demonstrating CNS and ocular delivery of RNAi therapeutics in rats and non-human primates.
Additional Business Updates
Expanded organization with key appointments and new hires.
Margaret Hamburg, former FDA Commissioner, to the Board of Directors, effective January 10, 2019. Concurrent with Dr. Hamburg’s appointment, Mr. John Clarkeis resigning from the Board after sixteen years of service.
Alnylam announces today the promotion of
Andy Orthas Senior Vice President, Head of U.S. In this role, he is responsible for commercial execution of Alnylam programs in the U.S. market. He was previously Alnylam’s Vice President of Commercial Operations, and joined the Company in 2016 from Biogen. Prior to Biogen, he held commercial and finance leadership roles at Genzyme and Amgen.
Alnylam also announces today the appointment of
Norton Oliveiraas Senior Vice President, Head of Latin America. He joins Alnylam from Gilead Scienceswhere he was Vice President for Latin Americaand the Caribbean. Prior to Gilead, Norton held commercial leadership roles at Merck/MSD and Shire.
- Appointed Dr.
In late 2018, Alnylam intends to:
Initiate a rolling submission of an NDA with the
FDAfor givosiran, with full clinical sections to be submitted in mid-2019, assuming positive results.
- Initiate the HELIOS-A Phase 3 study for ALN-TTRsc02 in hATTR amyloidosis.
- Initiate the Phase 1/2 study for ALN-AAT02 in alpha-1 liver disease.
- File a Clinical Trial Authorization (CTA) application for ALN-HBV02 (also known as VIR-2218), in partnership with Vir Biotechnology, for the treatment of chronic hepatitis B virus infection.
- Select its first CNS-targeted development candidate (DC) program.
R&D Day Investor Conferenceon December 6in New York City.
Financial results for the quarter ended
“We are pleased to have recognized initial revenue for an Alnylam
product for the first time in the Company’s history, following the
August FDA approval of ONPATTRO,” said
Cash and Investments
GAAP and Non-GAAP Net Loss
The net loss according to accounting principles generally accepted in the U.S. (GAAP) for the third quarter of 2018 was
The non-GAAP net loss for the third quarter of 2018 was
The non-GAAP net loss for the third quarter of 2018 and 2017 excludes stock-based compensation expense. See “Use of Non-GAAP Financial Measures” below for a description of non-GAAP financial measures and a reconciliation between GAAP and non-GAAP net loss appearing later in this press release.
ONPATTRO Revenues, Net
Net product revenues from sales of ONPATTRO were
Net Revenues from Collaborators
Net revenues from collaborators were
GAAP research and development (R&D) expenses were
Non-GAAP R&D expenses were
GAAP and Non-GAAP Selling, General and Administrative Expenses
GAAP selling, general and administrative (SG&A) expenses were
Non-GAAP SG&A expenses were
2018 Financial Guidance
Alnylam reiterates its expectations to end 2018 with approximately
The Company reiterates its expectations for 2018 annual non-GAAP R&D
expenses to be in the range of
Use of Non-GAAP Financial Measures
This press release contains non-GAAP financial measures, including expenses adjusted to exclude certain non-cash expenses and non-recurring gains 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 the press release are stock-based compensation expense and the gain on litigation settlement. 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 gain on litigation settlement because the Company believes this item is a one-time event occurring outside the ordinary course of the Company’s business.
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 GAAP and non-GAAP measures is provided later in this press release.
Conference Call Information
Management will provide an update on the Company and discuss third quarter 2018 and recent period results as well as expectations for the future via conference call on
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 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 LNP Technology
Alnylam has licenses to Arbutus Biopharma LNP intellectual property for use in RNAi therapeutic products using LNP technology.
About ONPATTRO™ (patisiran)
Patisiran, based on Nobel Prize-winning science, is an intravenously administered RNAi therapeutic targeting transthyretin (TTR) for the treatment of hereditary ATTR amyloidosis. It is designed to target and silence specific messenger RNA, potentially blocking the production of TTR protein before it is made. Patisiran blocks the production of transthyretin in the liver, reducing its accumulation in the body’s tissues in order to halt or slow down the progression of the disease. In
Important Safety Information
Infusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO. In a controlled clinical study, 19 percent of ONPATTRO-treated patients experienced IRRs, compared to 9 percent of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache.
To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, paracetamol, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.
Reduced Serum Vitamin A Levels and Recommended Supplementation
ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with ONPATTRO, as serum levels do not reflect the total vitamin A in the body.
Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness).
The most common adverse reactions that occurred in patients treated with ONPATTRO were respiratory-tract infection (29 percent) and infusion-related reactions (19 percent).
Alnylam (Nasdaq:ALNY) is leading the translation of RNA interference (RNAi) into a new class of innovative medicines with the potential to improve the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS) diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust discovery platform. ONPATTRO™ (patisiran) lipid complex injection, available in the U.S. for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults, is Alnylam’s first U.S.
Alnylam Forward Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, Alnylam's views with respect to the potential for RNAi therapeutics, including givosiran, ALN-TTRsc02, lumasiran, inclisiran, ALN-AAT02 and cemdisiran, its plans for additional regulatory filings and product launches for ONPATTRO, including in
With the exception of ONPATTRO (patisiran), none of Alnylam’s
investigational therapeutics have been approved by the
ALNYLAM PHARMACEUTICALS, INC.
UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS
(In thousands, except per share amounts)
|Three Months Ended
|Nine Months Ended
|Product revenues, net||$||460||$||—||$||460||$||—|
|Net revenues from collaborators||1,609||17,096||53,415||51,988|
|Cost and expenses:|
|Cost of goods sold||137||—||137||—|
|Research and development||139,945||95,252||374,384||272,863|
|Selling, general and administrative||116,545||47,644||273,671||131,910|
|Total costs and expenses||256,627||142,896||648,192||404,773|
|Loss from operations||(254,558)||(125,800)||(594,317)||(352,785)|
|Other income (expense):|
|Other income (expense)||2,925||(433)||5,468||(3,863)|
|Gain on litigation settlement||—||—||20,564||—|
|Total other income||9,721||2,863||44,723||4,138|
|Loss before income taxes||(244,837)||(122,937)||(549,594)||(348,647)|
|Provision for income taxes||(445)||—||(462)||—|
|Net loss per common share - basic and diluted||$||(2.43)||$||(1.34)||$||(5.48)||$||(3.93)|
|Weighted-average common shares used to compute basic and diluted net loss per common share||100,783||91,828||100,430||88,672|
|Unrealized gain (loss) on marketable securities, net of tax||415||218||1,041||(2,194)|
|Reclassification adjustment for realized loss on marketable securities included in net loss||—||—||—||1,894|
ALNYLAM PHARMACEUTICALS, INC.
RECONCILIATION OF SELECTED GAAP MEASURES TO NON-GAAP MEASURES
(In thousands, except per share amounts)
|Three Months Ended
|Nine Months Ended
|Reconciliation of GAAP to Non-GAAP Research and development:|
|GAAP Research and development||$||139,945||$||95,252||$||374,384||$||272,863|
|Less: Stock-based compensation expenses||(45,784)||(15,090)||(67,537)||(37,035)|
|Non-GAAP Research and development||$||94,161||$||80,162||$||306,847||$||235,828|
|Reconciliation of GAAP to Non-GAAP Selling, general and administrative:|
|GAAP Selling, general and administrative||$||116,545||$||47,644||$||273,671||$||131,910|
|Less: Stock-based compensation expenses||(42,170)||(10,865)||(62,242)||(28,667)|
|Non-GAAP Selling, general and administrative||$||74,375||$||36,779||$||211,429||$||103,243|
|Reconciliation of GAAP to Non-GAAP Operating costs and expenses:|
|GAAP Operating costs and expenses||$||256,627||$||142,896||$||648,192||$||404,773|
|Less: Stock-based compensation expenses||(87,954)||(25,955)||(129,779)||(65,702 )|
|Non-GAAP Operating costs and expenses||$||168,673||$||116,941||$||518,413||$||339,071|
|Reconciliation of GAAP to Non-GAAP Net loss:|
|GAAP Net loss||$||(245,282)||$||(122,937)||$||(550,056)||$||(348,647 )|
|Add: Stock-based compensation expenses||87,954||25,955||129,779||65,702|
|Less: Gain on litigation settlement||—||—||(20,564)||—|
|Non-GAAP Net loss||$||(157,328)||$||(96,982)||$||(440,841)||$||(282,945 )|
|Reconciliation of GAAP to Non-GAAP Net loss per common share-basic and diluted:|
|GAAP Net loss per common share - basic and diluted||$||(2.43)||$||(1.34)||$||(5.48)||$||(3.93)|
|Add: Stock-based compensation expenses||0.87||0.28||1.29||0.74|
|Less: Gain on litigation settlement||—||—||(0.20)||—|
|Non-GAAP Net loss per common share - basic and diluted||$||(1.56)||$||(1.06)||$||(4.39)||$||(3.19)|
ALNYLAM PHARMACEUTICALS, INC.
UNAUDITED CONDENSED CONSOLIDATED BALANCE SHEETS
(In thousands, except share amounts)
|September 30,||December 31,|
|Cash, cash equivalents and marketable debt securities||$||1,221,830||$||1,704,537|
|Accounts receivable, net||3,362||34,002|
|Prepaid expenses and other assets||121,904||44,291|
|Property, plant and equipment, net||272,652||181,900|
|Accounts payable, accrued expenses and other liabilities||$||119,671||$||104,905|
|Total deferred revenue||5,067||84,780|
|Total deferred rent||42,797||8,614|
|Total stockholders’ equity (101.0 million and 99.7 million common shares issued and outstanding at September 30, 2018 and December 31, 2017, respectively)||1,478,119||1,766,431|
|Total liabilities and stockholders' equity||$||1,675,654||$||1,994,730|
This selected financial information should be read in conjunction with
the consolidated financial statements and notes thereto included in
Alnylam’s Annual Report on Form 10-K which includes the audited
financial statements for the year ended
Alnylam Pharmaceuticals, Inc.
Christine Regan Lindenboom
(Investors and Media)