On November 7, 2018 Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), the leading RNAi therapeutics company, reported its consolidated financial results for the third quarter 2018 and reviewed recent commercial and R&D highlights (Press release, Alnylam, NOV 7, 2018, View Source [SID1234530997]).
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"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 John Maraganore, Ph.D., Chief Executive Officer of Alnylam. "Our recent regulatory and commercial launch experiences will be leveraged for our entire portfolio including late-stage programs such as givosiran, where we will initiate a rolling NDA submission this year; lumasiran, which we have advanced into late-stage development with the recent initiation of the ILLUMINATE-A Phase 3 study; and ALN-TTRsc02, which will enter Phase 3 later this year in the HELIOS-A study. We believe these accomplishments put us well on our way toward achieving our Alnylam 2020 goal of building a multi-product, global, commercial-stage company with a deep and sustainable clinical pipeline by the end of 2020."
"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 North America, Europe, Asia, and, soon, Latin America, along with established medical affairs and supply chain capabilities, positions us to expand our efforts in markets around the world," said Barry Greene, President of Alnylam. "We look forward to continuing our work toward strong commercial execution, with a focus on raising disease awareness, improving diagnosis, and bringing ONPATTRO to patients in need."
Third Quarter 2018 and Recent Period Significant Corporate Highlights
Commercial Highlights
Launched ONPATTRO (patisiran) in the U.S. and EU, initially in Germany.
Received 125 U.S. patient Start Forms as of September 30, 2018.
Recognized ONPATTRO revenue of $0.5 million for 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.
R&D Highlights
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 ONPATTRO for 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 and Medical Devices Agency and receipt of a Priority Review designation in Canada.
Published results from the APOLLO Phase 3 study of patisiran in the July 5, 2018 issue of The New England Journal of Medicine and APOLLO exploratory cardiac endpoint data in the September 14, 2018 issue 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, with FDA and 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.
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 Nephrology and the American Society of Nephrology annual meetings.
Announced alignment with the FDA on 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.
Alnylam’s partner, 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.
Reported new platform innovations at the Oligonucleotide Therapeutics Society 2018 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.
Appointed Dr. Margaret Hamburg, former FDA Commissioner, to the Board of Directors, effective January 10, 2019. Concurrent with Dr. Hamburg’s appointment, Mr. John Clarke is resigning from the Board after sixteen years of service.
Alnylam announces today the promotion of Andy Orth as 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 Oliveira as Senior Vice President, Head of Latin America. He joins Alnylam from Gilead Sciences where he was Vice President for Latin America and the Caribbean. Prior to Gilead, Norton held commercial leadership roles at Merck/MSD and Shire.
Upcoming Events
In late 2018, Alnylam intends to:
Initiate a rolling submission of an NDA with the FDA for 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.
Hold an R&D Day Investor Conference on December 6 in New York City.
Financial results for the quarter ended September 30, 2018
"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 Manmeet Soni, Chief Financial Officer of Alnylam. "With cash and investments on our balance sheet standing at $1.27 billion at September 30, and expectations to finish the year with approximately $1.0 billion, we believe Alnylam is in a strong position to continue executing on global commercial operations while advancing our pipeline programs through the clinic."
Cash and Investments
At September 30, 2018, Alnylam had cash, cash equivalents and marketable debt securities, and restricted investments, excluding equity securities, of $1.27 billion, as compared to $1.73 billion at December 31, 2017.
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 $245.3 million, or $2.43 per share on both a basic and diluted basis, as compared to a net loss of $122.9 million, or $1.34 per share on both a basic and diluted basis, for the same period in the previous year.
The non-GAAP net loss for the third quarter of 2018 was $157.3 million, or $1.56 per share on both a basic and diluted basis, as compared to a non-GAAP net loss of $97.0 million, or $1.06 per share on both a basic and diluted basis, for the same period in the previous year.
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 $0.5 million in the third quarter of 2018 following its approval by the FDA in August 2018.
Net Revenues from Collaborators
Net revenues from collaborators were $1.6 million in the third quarter of 2018 as compared to $17.1 million in the third quarter of 2017.
GAAP and Non-GAAP Research and Development Expenses
GAAP research and development (R&D) expenses were $139.9 million in the third quarter of 2018 as compared to $95.3 million in the third quarter of 2017.
Non-GAAP R&D expenses were $94.2 million in the third quarter of 2018 as compared to $80.2 million in the third quarter of 2017. Non-GAAP R&D expenses exclude stock-based compensation expense. A reconciliation between GAAP and non-GAAP R&D expenses appears later in this press release.
GAAP and Non-GAAP Selling, General and Administrative Expenses
GAAP selling, general and administrative (SG&A) expenses were $116.5 million in the third quarter of 2018 as compared to $47.6 million in the third quarter of 2017.
Non-GAAP SG&A expenses were $74.4 million in the third quarter of 2018 as compared to $36.8 million in the third quarter of 2017. Non-GAAP SG&A expenses exclude stock-based compensation expense. A reconciliation between GAAP and non-GAAP SG&A expenses appears later in this press release.
2018 Financial Guidance
Alnylam reiterates its expectations to end 2018 with approximately $1.0 billion of cash, cash equivalents and marketable debt securities, restricted cash and restricted investments, excluding equity securities.
The Company reiterates its expectations for 2018 annual non-GAAP R&D expenses to be in the range of $420 million to $460 million and non-GAAP SG&A expenses to be in the range of $280 million to $320 million. Both non-GAAP R&D and non-GAAP SG&A expenses exclude stock-based compensation expenses.
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 Wednesday, November 7, 2018 at 8:30 am ET. To access the call, please dial 800-667-5617 (domestic) or 334-323-0509 (international) five minutes prior to the start time and refer to conference ID 7650424. A replay of the call will be available beginning at 11:30 am ET on the day of the call. To access the replay, please dial 888-203-1112 (domestic) or 719-457-0820 (international) and refer to conference ID 7650424.