Alnylam Pharmaceuticals Reports Fourth Quarter and Full Year 2018 Financial Results and Highlights Recent Period Activity
− Achieved Fourth Quarter 2018 ONPATTRO® Global Net Product Revenues
− Obtained Regulatory Alignment on APOLLO-B Phase 3 Study of Patisiran in ATTR Amyloidosis with Cardiomyopathy and Initiated HELIOS-A Phase 3 Study to Advance Vutrisiran to Market, Supporting Plan for Sustained and Continuous Growth of ATTR Franchise –
− Advanced Additional Phase 3 Programs, Including Givosiran, with Rolling Submission of New Drug Application (NDA) Initiated and Topline ENVISION Phase 3 Results Expected in March, and Lumasiran, with ILLUMINATE-A Phase 3 Study Initiated –
− Maintained Strong Balance Sheet with $1.13 Billion in Cash as of Year-End 2018 –
− Provides 2019 Non-GAAP R&D and SG&A Expense Guidance –
“In 2018, we saw the approval and launch of ONPATTRO, the world’s first
RNAi therapeutic, heralding the arrival of a whole new class of
medicines. With our planned APOLLO-B Phase 3 study to support potential
expansion of ONPATTRO to ATTR amyloidosis patients with cardiomyopathy
and advancement of subcutaneously administered vutrisiran in the
HELIOS-A Phase 3 study, we are committing further efforts to help ATTR
amyloidosis patients and to support our plans for the sustained and
continued growth in our ATTR amyloidosis franchise for years to come,”
“We are pleased with our commercial progress to date, as we strive to
make ONPATTRO available to patients around the world. Specifically, we
are encouraged by our fourth quarter 2018 results, with over 200
patients receiving treatment with commercial ONPATTRO in the U.S. and EU
since launch, reflecting what we believe to be strong patient and
physician demand and excellent performance by our customer-facing field
Fourth Quarter 2018 and Recent Significant Corporate Highlights
Commercial Performance at Year-End 2018
Achieved global net product revenues for the fourth quarter of 2018 of
$12.1 millionfor ONPATTRO, and $12.5 millionfor the full year ended December 31, 2018.
Attained over 200 patients in the U.S. and EU on commercial ONPATTRO
- Including patients on commercial drug and patients in clinical studies and in the Company’s global Expanded Access Program (EAP), approximately 550 total patients worldwide were being treated with patisiran.
Received a total of 250 Start Forms in the U.S., with approximately 50
percent from patients not previously treated in the ONPATTRO EAP.
- Start Forms came from a diverse range of prescribing physician specialties, including 44 percent from neurologists, 35 percent from cardiologists, and 21 percent from other specialties.
For Start Forms received, 62 percent of patients were covered by
Medicare, 32 percent were covered by commercial insurers, and 6 percent were covered by other government insurers.
Continued significant progress with value-based agreements (VBAs) with
commercial payers in the U.S. and with market access efforts in the EU.
Since launch, Alnylam has completed definitive VBAs with
Harvard Pilgrim Healthcare, Humana, and another top five U.S. payer. Additional VBAs are under negotiation with over 15 other commercial payers with the potential to cover over 90 percent of commercial lives in the U.S.
The Company announces today that it has advanced pricing &
reimbursement procedures with authorities in 15 EU countries –
representing the vast majority of the hATTR amyloidosis
Europe– with positive feedback from several EU payers. Recent examples include positive technology assessment reports from authorities in Germanyand Sweden, the special innovation designation of ONPATTRO by the Italian authorities, and favorable alignment with authorities in The Netherlands, among others.
- Since launch, Alnylam has completed definitive VBAs with
Advanced patisiran (the non-branded name for ONPATTRO), an
intravenously administered investigational RNAi therapeutic in
development for the treatment of ATTR amyloidosis.
Continued global efforts to bring ONPATTRO to patients with filing
of a New Drug Submission (NDS) in
Canadaand a Marketing Authorisation Application (MAA) in Switzerland, which has now been accepted.
Obtained alignment with the
U.S. Food and Drug Administration( FDA) on the design of APOLLO-B, a randomized, double-blind, placebo-controlled Phase 3 study of patisiran in hereditary and wild-type ATTR amyloidosis patients with cardiomyopathy, with the goal of starting the trial in mid-2019.
- Continued global efforts to bring ONPATTRO to patients with filing of a New Drug Submission (NDS) in
Advanced vutrisiran (ALN-TTRsc02), a subcutaneously administered
investigational RNAi therapeutic in development for the treatment of
- Initiated HELIOS-A Phase 3 study in hereditary ATTR amyloidosis with polyneuropathy.
- Announced plans to initiate an additional Phase 3 study, HELIOS-B, of vutrisiran in hereditary and wild-type ATTR amyloidosis with cardiomyopathy in late 2019.
Advanced givosiran, an investigational RNAi therapeutic in development
for the treatment of acute hepatic porphyria (AHP).
Initiated rolling submission of a New Drug Application (NDA) with
plans to pursue full approval based on complete results – expected
March 2019– from the ENVISION Phase 3 study. Assuming positive results, the Company expects to submit full clinical sections to the FDAin mid-2019.
from Phase 1 study of givosiran in
The New England Journal of Medicine.
Presented updated positive
Phase 1/2 open-label extension (OLE) results at The Liver
Meeting® 2018 of the
American Association for the Study of Liver Diseases(AASLD).
- Initiated rolling submission of a New Drug Application (NDA) with plans to pursue full approval based on complete results – expected in
Advanced lumasiran, an investigational RNAi therapeutic in development
for the treatment of primary hyperoxaluria type 1 (PH1).
- Initiated ILLUMINATE-A, a global Phase 3 pivotal trial of lumasiran in children and adult PH1 patients with preserved renal function. 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( ESPN) and the American Society of Nephrology(ASN) annual 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.
Alnylam’s partner, The
Medicines Company, announced in January 2019that the Independent Data Monitoring Committee for the ongoing inclisiran Phase 3 clinical trials (ORION 9, 10, and 11) conducted its fifth 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 more than 2,450 patient-years of exposure to an RNAi therapeutic, representing the industry’s most comprehensive body of safety data for an RNA 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 programs.
- Discontinued a Phase 2 study of cemdisiran in atypical hemolytic uremic syndrome (aHUS) due to recruitment challenges. Alnylam announces today that it has received regulatory approval to initiate a Phase 2 study of cemdisiran in IgA nephropathy.
- 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). Alnylam announces today that it has initiated a Phase 1 study of ALN-AAT02, with initial results expected in 2019.
- With Vir Biotechnology, initiated a Phase 1/2 study of ALN-HBV02 (also known as VIR-2218), with initial results expected in 2019.
platform innovations at the
Oligonucleotide Therapeutics Society2018 Annual Meeting, including pre-clinical results demonstrating potent, wide-spread, and highly durable CNS and ocular delivery of RNAi therapeutics in rats and non-human primates.
- Selected its first CNS-targeted development candidate, ALN-APP, an investigational RNAi therapeutic targeting amyloid precursor protein (APP) for the treatment of cerebral amyloid angiopathy (CAA).
Additional Business Highlights
Entered into an exclusive distribution agreement with Medison Pharma
for the commercialization of certain RNAi therapeutics in
Resolved all litigation worldwide with
Upcoming Events in Early 2019
Alnylam expects to report topline results from the ENVISION Phase 3
study of givosiran in
March 2019, and announces today that it plans to present full study results in an oral presentation at the The International Liver Congress™ 2019 of the European Association for the Study of the Liver(EASL) on Saturday, April 13, 2019in Vienna, Austria.
Financial Results for the Quarter and Year Ended
“We ended 2018 with cash and investments on our balance sheet of
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 fourth quarter of 2018 was
The non-GAAP net loss for the fourth quarter of 2018 was
The non-GAAP net loss excludes stock-based compensation expense and gain on litigation settlement. 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
2019 Financial Guidance
Alnylam expects its 2019 annual non-GAAP R&D expenses to be in the range
The Company expects its current cash, cash equivalents, and marketable debt securities will support company operations for approximately two years based upon its current operating plan.
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.
The Company does not provide in this press release a reconciliation of its estimated 2019 non-GAAP R&D and non-GAAP SG&A expense guidance to the comparable GAAP measures because it is not able to estimate 2019 stock-based compensation expense without unreasonable efforts. The Company’s stock-based compensation expense is subject to significant fluctuations from period to period due to variability in the probability of performance-based vesting events for stock options and restricted stock units and changes in the Company’s stock price which materially impacts the recognition, timing of expense and fair value of these awards. In addition, we believe such reconciliations for our 2019 financial guidance would imply a degree of precision that would be confusing or misleading to investors.
Conference Call Information
Management will provide an update on the Company and discuss fourth
quarter and year end 2018 results as well as expectations for the future
via conference call on
Alnylam and Sanofi Genzyme, the specialty care global business unit of
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 TTR messenger RNA, thereby blocking the production of TTR
protein before it is made. Patisiran blocks the production of TTR 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).
About LNP Technology
Alnylam has licenses to Arbutus Biopharma LNP intellectual property for use in RNAi therapeutic products using LNP technology.
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.
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)/ocular 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 patisiran, vutrisiran, givosiran, lumasiran, inclisiran,
fitusiran, ALN-AAT02, cemdisiran, ALN-HBV02 and ALN-APP, its plans for
additional global regulatory filings and product launches for ONPATTRO,
its expectations regarding the completion of additional VBAs with U.S.
commercial payers and the status of pricing and reimbursement procedures
outside the U.S., its expectations regarding the timing for the
initiation of its APOLLO-B Phase 3 study of patisiran, its plans to
initiate the HELIOS-B Phase 3 study for vutrisiran in 2019, its
expectations regarding the timing and reporting of complete topline
results from the ENVISION Phase 3 study of givosiran and, if positive,
for the submission of full clinical sections of an NDA with the
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
|Product revenues, net||$||12,075||$||—||$||12,535||$||—|
|Net revenues from collaborators||8,958||37,924||62,373||89,912|
|Cost and expenses:|
|Cost of goods sold||1,665||—||1,802||—|
|Research and development||131,036||117,772||505,420||390,635|
|Selling, general and administrative||108,688||67,455||382,359||199,365|
|Total costs and expenses||241,389||185,227||889,581||590,000|
|Loss from operations||(220,356)||(147,303)||(814,673)||(500,088)|
|Other income (expense):|
|Other (expense) income||(1,295)||841||4,173||(3,022)|
|Gain on litigation settlement||—||—||20,564||—|
|Total other income||9,276||5,076||53,999||9,214|
|Loss before income taxes||(211,080)||(142,227)||(760,674)||(490,874)|
|Provision for income taxes||(361)||—||(823)||—|
|Net loss per common share - basic and diluted||$||(2.09)||$||(1.48)||$||(7.57)||$||(5.42)|
|Weighted-average common shares used to compute basic and diluted net loss per common share||101,066||96,139||100,590||90,554|
|Unrealized gain (loss) on marketable securities, net of tax||179||(692)||1,220||(2,886)|
|Reclassification adjustment for realized loss on marketable securities included in net loss||—||—||—||1,894|
ALNYLAM PHARMACEUTICALS, INC.
RECONCILIATION OF SELECTED GAAP MEASURES TO NON-GAAP MEASURES
(In thousands, except per share amounts)
Three Months Ended
|Reconciliation of GAAP to Non-GAAP Research and development:|
|GAAP Research and development||$||131,036||$||117,772||$||505,420||$||390,635|
|Less: Stock-based compensation expenses||(12,972)||(14,837)||(80,509)||(51,872)|
|Non-GAAP Research and development||$||118,064||$||102,935||$||424,911||$||338,763|
|Reconciliation of GAAP to Non-GAAP Selling, general and administrative:|
|GAAP Selling, general and administrative||$||108,688||$||67,455||$||382,359||$||199,365|
|Less: Stock-based compensation expenses||(15,001)||(12,280)||(77,243)||(40,947)|
|Non-GAAP Selling, general and administrative||$||93,687||$||55,175||$||305,116||$||158,418|
|Reconciliation of GAAP to Non-GAAP Operating costs and expenses:|
|GAAP Operating costs and expenses||$||241,389||$||185,227||$||889,581||$||590,000|
|Less: Stock-based compensation expenses||(27,973)||(27,117)||(157,752)||(92,819)|
|Non-GAAP Operating costs and expenses||$||213,416||$||158,110||$||731,829||$||497,181|
|Reconciliation of GAAP to Non-GAAP Net loss:|
|GAAP Net loss||$||(211,441)||$||(142,227)||$||(761,497)||$||(490,874)|
|Add: Stock-based compensation expenses||27,973||27,117||157,752||92,819|
|Less: Gain on litigation settlement||—||—||(20,564)||—|
|Non-GAAP Net loss||$||(183,468)||$||(115,110)||$||(624,309)||$||(398,055)|
|Reconciliation of GAAP to Non-GAAP Net loss per common share-basic and diluted:|
|GAAP Net loss per common share - basic and diluted||$||(2.09)||$||(1.48)||$||(7.57)||$||(5.42)|
|Add: Stock-based compensation expenses||0.27||0.28||1.57||1.02|
|Less: Gain on litigation settlement||—||—||(0.21)||—|
|Non-GAAP Net loss per common share - basic and diluted||$||(1.82)||$||(1.20)||$||(6.21)||$||(4.40)|
ALNYLAM PHARMACEUTICALS, INC.
UNAUDITED CONDENSED CONSOLIDATED BALANCE SHEETS
(In thousands, except share amounts)
|December 31,||December 31,|
|Cash, cash equivalents and marketable debt securities||$||1,082,949||$||1,704,537|
|Accounts receivable, net||18,760||34,002|
|Prepaid expenses and other assets||83,542||44,291|
|Property, plant and equipment, net||320,658||181,900|
|Accounts payable, accrued expenses and other liabilities||$||177,392||$||104,905|
|Total deferred revenue||3,954||84,780|
|Total deferred rent||61,491||8,614|
|Total stockholders’ equity (101.2 million and 99.7 million common shares issued and outstanding at December 31, 2018 and December 31, 2017, respectively)||1,301,965||1,766,431|
|Total liabilities and stockholders' equity||$||1,574,802||$||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)