On February 15, 2024 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, reported its consolidated financial results for the fourth quarter and full year ended December 31, 2023 and reviewed recent business highlights (Press release, Alnylam, FEB 15, 2024, View Source [SID1234640136]).
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"2023 was a year of strong execution at Alnylam. We delivered robust product revenue growth across our four wholly-owned commercial medicines, with $1.24 billion in global net product revenues, and achieved over 5,000 patients now being treated with an Alnylam commercial medicine. We also extended our leadership in RNAi with the first clinical demonstration of gene silencing in the human brain using an RNAi therapeutic, strengthened our business for the future through a landmark partnership with Roche and delivered solid financial performance," said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam. "Looking ahead to 2024, we are excited for a number of important milestones across the pipeline, including results from the HELIOS-B Phase 3 study of vutrisiran as well as the KARDIA-2 Phase 2 study of zilebesiran, and six clinical study starts. This progress sets us up for delivering on our Alnylam P5x25 goals of becoming a top-tier biotech company delivering sustained innovation and exceptional financial results."
Fourth 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 fourth quarter of $79 million and $175 million, respectively, representing 10% total TTR quarterly growth compared to Q3 2023, and full year 2023 revenues of $355 million and $558 million, respectively, representing 40% total TTR annual growth compared to full year 2022.
Attained over 4,060 hATTR amyloidosis patients with polyneuropathy worldwide on commercial treatment with ONPATTRO or AMVUTTRA as of December 31, 2023.
Total Ultra-Rare: GIVLAARI (givosiran) & OXLUMO (lumasiran)
Achieved global net product revenues for GIVLAARI and OXLUMO for the fourth quarter of $59 million and $33 million, respectively, representing 11% total Ultra-Rare quarterly growth compared to Q3 2023, and full year 2023 revenues of $219 million and $110 million, respectively, representing 35% total Ultra-Rare annual growth compared to full year 2022.
Attained over 650 patients on commercial GIVLAARI and over 430 patients on commercial OXLUMO worldwide as of December 31, 2023.
R&D Highlights
Alnylam announces today updates to the statistical analysis plan for the HELIOS-B Phase 3 study of vutrisiran in patients with ATTR amyloidosis with cardiomyopathy. These will include updates to the primary and secondary endpoint structure, as well as study exposure. Topline results are expected to be available in late June or early July. Details will be discussed on the conference call this morning.
Published results from Phase 3 APOLLO-B study of patisiran in the New England Journal of Medicine.
Presented positive initial Phase 1 results with ALN-TTRsc04 demonstrating rapid knockdown achieved by a single dose with mean serum TTR reduction up to 97%, with durability supporting potential for annual dosing and an encouraging safety profile.
Presented positive results from the KARDIA-1 Phase 2 dose-ranging study of zilebesiran, an investigational RNAi therapeutic in development to treat hypertension patients at high cardiovascular risk, during the American Heart Association (AHA) Scientific Sessions.
Announces today that the U.S. Food and Drug Administration (FDA) has provided clearance to initiate the multiple-dose part (Part B) of the ongoing Phase 1 study of ALN-APP, an investigational RNAi therapeutic targeting amyloid precursor protein (APP) in development for the treatment of Alzheimer’s disease and cerebral amyloid angiopathy. The FDA has confirmed that multiple-dosing in the Phase 1 study may proceed at doses up to 180 mg given every six months, which covers all dose regimens planned to be explored in Part B. A partial clinical hold remains for higher or more frequent dosing regimens.
Reported updated positive interim results for the ongoing single ascending dose portion of the Phase 1 study of ALN-APP in patients with early-onset Alzheimer’s disease at the 2023 Alzheimer’s Association International Conference and at the 16th Clinical Trials in Alzheimer’s Disease conference.
Presented positive initial Phase 1 results with ALN-KHK demonstrating robust target engagement and an encouraging safety profile, supporting continued development as a novel treatment for type 2 diabetes mellitus.
Filed an Investigational New Drug (IND) application for ALN-BCAT, an investigational RNAi therapeutic targeting β-catenin in development for the treatment of hepatocellular carcinoma.
Sanofi presented positive results from the ATLAS-OLE Phase 3 extension study of fitusiran, demonstrating a substantially improved safety profile and consistent bleed protection in people with hemophilia A or B, with or without inhibitors. Specifically, the risk of thrombosis was reduced, with rates comparable to those reported in the general hemophilia population.
Sanofi expects to submit a New Drug Application (NDA) to the FDA in 2024.
Additional Business Updates
Ranked #1 on Boston Globe’s Top Places to Work list for 2023 in the "Largest Employer" category.
Recognized by Science magazine as a Top Employer for the fifth consecutive year.
Upcoming Events
Alnylam announces today that results from the KARDIA-2 Phase 2 study of zilebesiran will be presented in a Late-Breaker presentation at the American College of Cardiology Scientific Sessions 2024 on April 7, 2024 in Atlanta, Georgia.
In early 2024, Alnylam intends to:
Report topline results from the HELIOS-B Phase 3 study of vutrisiran in late June or early July.
Initiate the KARDIA-3 Phase 2 study of zilebesiran.
Initiate a Phase 2 study of ALN-APP in patients with cerebral amyloid angiopathy.
Initiate Part B of the Phase 1 study of ALN-KHK.
Initiate a Phase 1 study of ALN-BCAT.
Financial Highlights for the Fourth Quarter and Year End 2023
Three Months Ended
December 31,
Twelve Months Ended
December 31,
(In thousands, except per share amounts)
2023
2022
2023
2022
Net product revenues
$
346,288
$
261,675
$
1,241,474
$
894,329
Net revenue from collaborations
$
76,407
$
70,645
$
546,185
$
134,912
Royalty revenue
$
17,023
$
2,715
$
40,633
$
8,177
GAAP Operating loss
$
(116,404
)
$
(188,614
)
$
(282,175
)
$
(785,072
)
Non-GAAP Operating loss
$
(74,410
)
$
(145,847
)
$
(60,495
)
$
(554,423
)
GAAP Net loss
$
(137,870
)
$
(207,493
)
$
(440,242
)
$
(1,131,156
)
Non-GAAP Net loss
$
(96,643
)
$
(171,522
)
$
(201,618
)
$
(790,609
)
GAAP Net loss per common share – basic and diluted
$
(1.10
)
$
(1.68
)
$
(3.52
)
$
(9.30
)
Non-GAAP Net loss per common share – basic and diluted
$
(0.77
)
$
(1.39
)
$
(1.61
)
$
(6.50
)
For an explanation of our use of non-GAAP financial measures refer to the "Use of Non-GAAP Financial Measures" section later in this press release and for a reconciliation of each non-GAAP financial measure to the most comparable GAAP measures, see the table at the end of this press release.
Net Product Revenues
Three Months Ended
December 31,
Twelve Months Ended
December 31,
(In thousands)
2023
2022
2023
2022
ONPATTRO net product revenues
$
79,006
$
122,221
$
354,546
$
557,608
AMVUTTRA net product revenues
175,254
68,566
557,838
93,795
Total TTR net product revenues
254,260
190,787
912,384
651,403
GIVLAARI net product revenues
59,298
47,058
219,251
173,144
OXLUMO net product revenues
32,730
23,830
109,839
69,782
Total net product revenues
$
346,288
$
261,675
$
1,241,474
$
894,329
Year over Year % Growth
Three Months Ended
December 31, 2023
Twelve Months Ended
December 31, 2023
As Reported
At CER*
As Reported
At CER*
Total TTR net product revenues
33
%
31
%
40
%
40
%
GIVLAARI net product revenues
26
%
24
%
27
%
26
%
OXLUMO net product revenues
37
%
32
%
57
%
55
%
Total net product revenues
32
%
30
%
39
%
39
%
* CER = Constant Exchange Rate, representing growth calculated as if the exchange rates had remained unchanged from those used in 2022. CER is a non-GAAP measure.
Net product revenues increased 32% and 39% at actual currency during the three and twelve months ended December 31, 2023, respectively, compared to the same periods in 2022, and 30% and 39% at CER, respectively. The increases are primarily due to increased patients on our commercial TTR therapies driven by the launch of AMVUTTRA 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 8% and 305% during the three and twelve months ended December 31, 2023, respectively, as compared to the same periods in 2022, primarily due to revenue recognized under our Collaboration and License Agreement with Roche, as executed in July 2023, and revenue recognized under our Novartis Collaboration Agreement associated with the achievement of specified commercialization and regulatory milestones.
Operating Expenses
Three Months Ended
December 31,
Twelve Months Ended
December 31,
(In thousands)
2023
2022
2023
2022
Cost of goods sold
$
71,975
$
46,172
$
268,216
$
140,174
Cost of goods sold as a percentage of net product revenues
20.8
%
17.6
%
21.6
%
15.7
%
Cost of collaborations and royalties
$
13,883
$
5,094
$
42,190
$
28,643
GAAP research and development expenses
$
272,141
$
262,039
$
1,004,415
$
883,015
Non-GAAP research and development expenses
$
253,056
$
245,095
$
907,142
$
790,854
GAAP selling, general and administrative expenses
$
198,123
$
210,344
$
795,646
$
770,658
Non-GAAP selling, general and administrative expenses
$
175,214
$
184,521
$
671,239
$
632,170
Cost of Goods Sold
Cost of goods sold as a percentage of net product revenues increased during the three and twelve months ended December 31, 2023, respectively, as compared to the same periods in 2022, primarily due to increased volume and rate of royalties payable on net sales of AMVUTTRA associated with tiered royalty percentages, in addition to increased excess and obsolete charges primarily due to canceling manufacturing commitments and the impairment of ONPATTRO inventory that had been manufactured for future demand associated with the ATTR amyloidosis with cardiomyopathy indication for patisiran for which we did not receive regulatory approval.
Research & Development (R&D) Expenses
GAAP and non-GAAP R&D expenses increased during the three and twelve months ended December 31, 2023, compared to the same periods in 2022, primarily due to increased headcount and infrastructure expenses to support our R&D pipeline, development expenses associated with the KARDIA-1 and KARDIA-2 zilebesiran Phase 2 studies, and manufacturing and research related expenses associated with our pre-clinical and developmental activities. GAAP R&D expenses further increased during the twelve month period due to increased stock-based compensation expense related to the accounting for certain performance-based awards during the period.
Selling, General & Administrative (SG&A) Expenses
GAAP and non-GAAP SG&A expenses decreased during the three months ended December 31, 2023, compared to the same period in 2022, primarily due to increased legal expenses in 2022 associated with the Patent Infringement Lawsuits we filed in March 2022 and the Department of Justice investigation, which closed in August 2023, and increased expenses in support of the global launch of AMVUTTRA in the third quarter of 2022.
GAAP and non-GAAP SG&A expenses increased during the twelve months ended December 31, 2023, compared to the same period in 2022, primarily due to increased headcount and other strategic investments in support of the global launch of AMVUTTRA and other expenses to support our strategic growth.
Other Financial Highlights
Cash, cash equivalents and marketable securities were $2.44 billion as of December 31, 2023, compared to $2.19 billion as of December 31, 2022, with the increase primarily due to the receipts of a $310 million upfront payment from Roche in connection with our partnership to co-develop and co-commercialize zilebesiran, a $100 million payment from Regeneron in connection with the achievement of certain criteria during early clinical development for our CNS program, ALN-APP, and nearly $150 million from employee option award exercises, offset by our operating loss for the year.
A reconciliation of our GAAP to non-GAAP results for the current quarter is included in the tables at the end of this press release.
2024 Financial Guidance
Full year December 31, 2024 financial guidance consists of the following:
Combined net product revenues for AMVUTTRA, ONPATTRO, GIVLAARI and OXLUMO1
$1,400 million – $1,500 million
Net Product Revenue Growth vs. 2023 at reported Fx rates1
13% – 21%
Net Product Revenue Growth vs. 2023 at constant exchange rates*
13% – 21%
Net revenues from collaborations and royalties
$325 million – $425 million
GAAP R&D and SG&A expenses
$1,900 million – $2,050 million
Non-GAAP R&D and SG&A expenses2
$1,675 million – $1,775 million
1 Uses January 31, 2024 FX rates including: 1 EUR = 1.08 USD and 1 USD = 147 JPY
2 Primarily excludes $225-$275 million of stock-based compensation expense from estimated GAAP R&D and SG&A expenses.
* CER = Constant Exchange Rate, representing growth calculated as if the exchange rates had remained unchanged from those used in the twelve months ended December 31, 2023. CER is a non-GAAP measure.