On March 1, 2022 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported financial results for the full year and fourth quarter of 2021 and provided financial guidance for 2022 (Press release, Jazz Pharmaceuticals, MAR 1, 2022, View Source [SID1234609306]).

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"2021 was a transformative year for Jazz, delivering over $3 billion in revenue for the first time. Our talented team achieved our goal of five key launches through 2020 and 2021, delivering innovative medicines to patients in critical need. We also acquired and integrated GW Pharmaceuticals, which expanded our commercial portfolio with Epidiolex, enhanced our R&D capabilities and talent, and added the industry-leading GW cannabinoid platform," said Bruce Cozadd, chairman and chief executive officer of Jazz Pharmaceuticals. "These accomplishments underscore a significant advance in Jazz’s evolution to an innovative global biopharmaceutical company. We expect these achievements, coupled with our expanded capabilities and disciplined capital allocation, to drive sustainable growth and enhanced value as part of Vision 2025, which we announced in January. As we begin 2022, we remain focused on growing and diversifying our revenue, investing in our pipeline of novel therapies and delivering innovative therapies for patients."

"In 2021, our R&D organization advanced key programs across our portfolio, further broadening our pipeline into disease areas with significant unmet patient need and market potential. In the fourth quarter, we made important progress with key programs, including Phase 2 trial initiations in essential tremor and PTSD. Jazz and its partners also initiated multiple clinical trials to evaluate Zepzelca together with Tecentriq in first-line extensive stage small cell lung cancer (SCLC), and in its current indication in second-line SCLC. We were also pleased to have submitted a Supplemental Biologics License Application (sBLA) for Rylaze for Monday/Wednesday/Friday intramuscular dosing at the end of January, which will be reviewed under the Real-Time Oncology Review (RTOR) program," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "Our R&D productivity, which has been strengthened by investment in our organization and the addition of GW programs and expertise, positions us well to deliver at least five additional novel product approvals by the end of the decade, a key component of Vision 2025."

Key Highlights

Commercial and R&D Excellence

Positive early feedback underpins November 2021 launch of Xywav for idiopathic hypersomnia
Drove exceptional Xywav adoption in narcolepsy in 2021
Epidiolex/Epidyolex year-over-year revenue growth1 of 29% underscores blockbuster potential
Rapidly established Zepzelca as the treatment of choice in second-line SCLC
Rylaze launch progressing well with strong early demand
Significant revenue diversification with 59% of net product sales in 4Q21 from products launched or acquired since 2019
Advanced value-driving pipeline programs with 5 key trials initiated in 2H21
Entering 2022 well-positioned to deliver on Vision 2025
Financial

Growing and durable commercial franchises drove 2021 total revenues of $3.1 billion; 31% increase compared to 2020
Significant deleveraging accomplished following GW acquisition:
Net leverage ratio at 4.1x as of December 31, 20212
0.8x improvement in 8 months following close of GW transaction
On-track for target of less than 3.5x by the end of 2022
Meaningful top- and bottom-line growth expected with 2022 total revenue guidance of $3.46 to $3.66 billion
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1.

On a proforma basis

2.

On a non-GAAP adjusted basis. Non-GAAP net leverage ratio is a non-GAAP financial measure. For further information, see " Non-GAAP Financial Measures."

Business Updates

Key Commercial Products

Oxybate (Xywav and Xyrem):

Net product sales for the combined oxybate business increased 3% to $1,801.1 million in 2021 and increased 4% to $471.4 million in 4Q21 compared to the same periods in 2020.
Average active oxybate patients on therapy was approximately 16,200 in 4Q21, an increase of approximately 6% compared to the same period in 2020.
Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution:

Xywav net product sales were $535.3 million in 2021 and $182.7 million in 4Q21.
There were approximately 6,900 active Xywav patients exiting 4Q21.
Xywav has broad patent protection to 2033.
Xywav for Narcolepsy:

In 2021, the Company drove market-leading adoption of Xywav in narcolepsy.
There were approximately 6,650 active Xywav patients with narcolepsy exiting 4Q21.
In June 2021, FDA recognized seven years of Orphan Drug Exclusivity (ODE), through July 2027, for Xywav and published its summary of clinical superiority findings stating that "Xywav is clinically superior to Xyrem by means of greater safety because Xywav provides a greatly reduced chronic sodium burden compared to Xyrem." Further, FDA stated that "the differences in the sodium content of the two products at the recommended doses will be clinically meaningful in reducing cardiovascular morbidity in a substantial proportion of patients for whom the drug is indicated."
Xywav for Idiopathic Hypersomnia (IH):

The Company launched Xywav for IH on November 1, 2021, with initial launch efforts focused on the approximately 37,000 currently diagnosed patients in the U.S. who are actively seeking healthcare.
Positive early launch momentum with approximately 250 active Xywav patients with IH exiting 4Q21. Healthcare providers are excited to have a treatment option with positive and compelling clinical trial results that address IH and not just its symptoms.
FDA recognized ODE for IH in January 2022 extending to August 2028.
Xyrem (sodium oxybate) oral solution:

Xyrem net product sales decreased 27% to $1,265.8 million in 2021 and decreased 34% to $288.8 million in 4Q21 compared to the same periods in 2020, reflecting the continued strong adoption of Xywav.
Epidiolex/Epidyolex (cannabidiol):

Epidiolex/Epidyolex net product sales were $463.6 million in 2021, or $658.3 million on a proforma basis, and $193.8 million in 4Q21. On a proforma basis, these net product sales represent growth of 29% and 35% compared to 2020 and 4Q20 respectively.
Net product sales in 4Q21 were favorably impacted by approximately $18 million, compared to 3Q21, relating to a temporary increase in specialty pharmacy inventory levels.
Epidyolex is now commercially available and fully reimbursed in four of the five key European markets: United Kingdom, Germany, Italy and Spain, with an anticipated launch in France in 2022. The Company has made significant progress on its European rollout with launches in Spain, Italy and Switzerland in 3Q21 and Ireland in 1Q22.
The Company expects to initiate a Phase 3 pivotal trial of Epidiolex for Epilepsy with Myoclonic-Atonic Seizures (EMAS), the fourth target indication for Epidiolex, in 1H22.
The Company continues to strengthen the IP durability of Epidiolex. The U.S. FDA Orange Book Listed patent (US 11,207,292) was granted in December 2021, and extends through 2039. This patent covers the composition of the botanically derived cannabidiol (CBD) preparation used in Epidiolex and the treatment of indicated disorders using that CBD preparation.
Zepzelca (lurbinectedin):

Zepzelca net product sales were $246.8 million in 2021, the first full calendar year on the market following launch in July 2020, and increased 21% to $64.8 million in 4Q21 compared to 4Q20.
The Company is pleased to have established Zepzelca as the treatment of choice in the second-line SCLC setting after only eighteen months on the market.
Zepzelca development program updates:
The Company has initiated the Phase 2 basket trial evaluating Zepzelca as monotherapy in select relapsed/refractory solid tumors.
Jazz and collaborator F. Hoffmann-La Roche Ltd (Roche) have initiated a Phase 3 trial to evaluate first-line use of Zepzelca in combination with Tecentriq (atezolizumab), compared to Tecentriq alone, as maintenance therapy, in patients with extensive-stage SCLC after induction chemotherapy. The first patient was enrolled in November 2021.
The Company’s partner, PharmaMar, initiated a confirmatory trial, LAGOON, in second-line SCLC in December 2021. If positive, this trial would confirm the benefit of Zepzelca in the treatment of SCLC when patients progress following first-line treatment with a platinum-based regimen.
Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn):

Rylaze net product sales were $85.6 million in 2021 and $65.0 million in 4Q21, following commercial launch on July 15, 2021. 2021 revenues reflect the strong demand for Rylaze and include initial inventory build.
In January 2022, the Company completed the submission of an sBLA to FDA seeking approval for a Monday/Wednesday/Friday (M/W/F) intramuscular dosing schedule for Rylaze. The submission will be reviewed under the RTOR program.
The Company presented initial data, for the first time, from the Phase 2/3 study of Rylaze in patients with acute lymphoblastic leukemia and lymphoblastic lymphoma who developed hypersensitivity or silent inactivation to a long-acting E. coli–derived asparaginase, at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2021. This data showed that with the proposed M/W/F dosing schedule, patients maintain a clinically meaningful level of nadir serum asparaginase activity through the entire duration of treatment.
The Company anticipates that data from the current development program will support regulatory filings in Europe in mid-2022, including intravenous (IV) administration, with potential for approval in 2023, as well as a further submission to FDA to support IV administration later this year. The Company is also working with a partner to advance the program for potential submission, approval and launch in Japan.
Key Pipeline Highlights

Nabiximols:

The Company initiated the third Phase 3 nabiximols clinical trial, NCT04984278, in multiple sclerosis (MS)-related spasticity in 3Q21. This is a randomized, double-blind, placebo-controlled trial with a primary endpoint of muscle tone, expected to enroll approximately 190 patients.
The Company anticipates data from its first Phase 3 trial, NCT04657666, in 1H22; positive findings may enable a New Drug Application submission to FDA in 2022. Data from the two additional Phase 3 trials will follow in late 2022 and early 2023.
Suvecaltamide (JZP385):

Suvecaltamide, a highly selective modulator of T-type calcium channels, is in clinical development for the treatment of essential tremor.
The Company initiated a Phase 2b trial in 4Q21 and announced that the first patient was enrolled in December 2021. Top-line data read-out is anticipated in 1H24.
JZP150:

JZP150, a selective fatty acid amide hydrolase, or FAAH, inhibitor, is in clinical development for the potential treatment of post-traumatic stress disorder (PTSD).
The Company initiated a Phase 2 trial in 4Q21 and announced that the first patient was enrolled in December 2021. Top-line data read-out is anticipated in late 2023.
The Company received Fast Track Designation for JZP150 development in PTSD from FDA in 4Q21, underscoring the significant unmet medical needs of patients.
Other Products

Sunosi (solriamfetol):

Sunosi net product sales increased by 104% to $57.9 million in 2021 and increased 71% to $14.9 million in 4Q21 compared to the same periods in 2020.
In 4Q21, U.S. prescriptions increased by 4% compared to 3Q21.
Vyxeos (daunorubicin and cytarabine) liposome for injection:

Vyxeos net product sales increased 11% to $134.1 million in 2021 and increased 12% to $34.8 million in 4Q21 compared to the same periods in 2020.
Defitelio (defibrotide sodium) / defibrotide:

Defitelio/defibrotide net product sales increased 1% to $197.9 million in 2021 and decreased 23% to $42.5 million in 4Q21 compared to the same periods in 2020 due to the timing of distributor orders.
Financial Highlights

Commencing in 2020, following consultation with the staff of the Division of Corporation Finance of the U.S. Securities and Exchange Commission, the Company no longer excludes upfront and milestone payments from the Company’s non-GAAP adjusted net income, its line item components and non-GAAP adjusted EPS. See "Non-GAAP Financial Measures" below.

GAAP net income (loss) for 2021 was ($329.7 million), or ($5.52) per diluted share, compared to $238.6 million, or $4.22 per diluted share, for 2020. GAAP net income (loss) for 4Q21 was ($35.4 million), or ($0.57) per diluted share, compared to $133.4 million, or $2.33 per diluted share, for 4Q20.

Non-GAAP adjusted net income for 2021 was $992.8 million, or $16.23 per diluted share, compared to $704.0 million, or $12.46 per diluted share, for 2020. Non-GAAP adjusted net income for 4Q21 was $262.0 million, or $4.21 per diluted share, compared to $228.7 million, or $4.00 per diluted share, for 4Q20.

Reconciliations of applicable GAAP reported to non-GAAP adjusted information are included at the end of this press release.

Total Revenues

Net product sales for Epidiolex/Epidyolex and Sativex are included from the acquisition of GW Pharmaceuticals plc (GW Acquisition) on May 5, 2021.

Total revenues increased 31% in 2021 and 35% in 4Q21 compared to the same periods in 2020.

Products launched or acquired since 2019 comprised 59% of total net product sales in 4Q21.
Neuroscience net product sales in 2021 increased 31% to $2,335.4 million compared to 2020 primarily driven by Epidiolex/Epidyolex net product sales in 2021 of $463.6 million, following the GW Acquisition. In 2021, oxybate net product sales increased 3% to $1,801.1 million led by strong Xywav net product sales of $535.3 million partially offset by a decrease in Xyrem net product sales as a result of the strong adoption of Xywav by existing Xyrem patients. Neuroscience net product sales in 4Q21 increased 48% to $684.8 million compared to the same period in 2020 primarily driven by Epidiolex/Epidyolex net product sales in 4Q21 of $193.8 million. In 4Q21, oxybate net product sales increased 4% to $471.4 million.
Oncology net product sales in 2021 increased 32% to $733.8 million compared to 2020 primarily driven by an increase in Zepzelca net product sales of $156.4 million, following launch in the U.S. in July 2020. Oncology net product sales in 4Q21 increased 5% to $207.1 million compared to the same period in 2020 primarily driven by an increase in Zepzelca net product sales of $11.4 million.
Operating Expenses and Effective Tax Rate

Operating expenses changed over the prior year periods primarily due to the following:

Cost of product sales increased in 2021 and in 4Q21 compared to the same periods in 2020, on a GAAP and on a non-GAAP adjusted basis, due to increased net product sales as a result of the GW Acquisition. In addition, acquisition accounting inventory fair value step-up expense of $223.1 million in 2021 and $74.4 million in 4Q21 impacted GAAP cost of product sales.
Selling, general and administrative (SG&A) expenses increased in 2021 and in 4Q21 compared to the same periods in 2020, on a GAAP and on a non-GAAP adjusted basis, primarily due to an increase in compensation-related expenses driven by higher headcount as a result of the GW Acquisition and increased investment to support the Company’s recent product launches. SG&A expenses in 2021 and in 4Q21 on a GAAP basis also included transaction and integration related expenses of $229.0 million and $37.8 million related to the GW Acquisition.
Research and development (R&D) expenses increased in 2021 and in 4Q21 compared to the same periods in 2020, on a GAAP and on a non-GAAP adjusted basis, primarily due to the addition of costs related to clinical programs for nabiximols, Epidiolex and cannabinoids, an increase in costs related to suvecaltamide (JZP385) and JZP150, an increase in compensation-related expenses due to higher headcount primarily driven by the GW Acquisition and milestone expense of $10.0 million in 4Q21 relating to our asset purchase and collaboration agreements with Redx Pharma.
Acquired in-process research and development (IPR&D) expense in 2020 on a GAAP and on a non-GAAP adjusted basis primarily related to a $200.0 million upfront payment to PharmaMar for the exclusive U.S. commercialization and development rights to Zepzelca and a $35.0 million upfront payment to SpringWorks Therapeutics, Inc., in the fourth quarter, for a FAAH inhibitor program.
In 2020, the Company recorded an impairment charge of $136.1 million on a GAAP basis following the Company’s decision to stop enrollment in its Phase 3 clinical study of defibrotide for the prevention of veno-occlusive disease due to an Independent Data Monitoring Committee determination that it was highly unlikely that the study would reach its primary endpoint.
Cash Flow and Balance Sheet

As of December 31, 2021, cash and cash equivalents were $591.4 million, and the outstanding principal balance of the Company’s long-term debt was $6.4 billion compared to $6.6 billion as of September 30, 2021. In addition, the Company had undrawn borrowing capacity under a revolving credit facility of $500.0 million. For the year ended December 31, 2021, the Company generated $778.5 million of cash from operations. In 4Q21 the Company made another voluntary payment of $251 million on its term loan B.

2022 Financial Guidance

Following the adoption of ASU 2020-06, diluted EPS must be calculated using the if-converted method which assumes full conversion of our Exchangeable Senior Notes. Diluted EPS calculations for 2022 include 9 million shares related to the assumed conversion of the Exchangeable Senior Notes and the associated interest expense add-back to net income of $29 million, on a GAAP basis, and $25 million on a non-GAAP basis, under the "if converted" method.

Non-GAAP adjusted EPS guidance for 2022 reflects dilution of approximately $2.00 post adoption of ASU 2020-06.

As illustrated below, had ASU 2020-06 been adopted in 2021, the impact on adjusted EPS for the year ended December 31, 2021 would have been a reduction of $1.73 to $14.47. There would have been no impact on GAAP net loss per diluted share as it was anti-dilutive.

Conference Call Details

Jazz Pharmaceuticals will host an investor conference call and live audio webcast today at 4:30 p.m. ET (9:30 p.m. GMT) to provide a business and financial update and discuss its 2021 full year and 4Q21 results and provide 2022 financial guidance. The live webcast may be accessed from the Investors section of the Company’s website at www.jazzpharma.com. Please connect to the website prior to the start of the conference call to ensure adequate time for any software downloads that may be necessary. Investors may participate in the conference call by dialing +1 855 353 7924 in the U.S., or +1 503 343 6056 outside the U.S., and entering passcode 6895455.

A replay of the conference call will be available through March 8, 2022 by dialing +1 855 859 2056 in the U.S., or +1 404 537 3406 outside the U.S., and entering passcode 6895455. An archived version of the webcast will be available for at least one week in the Investors section of the Company’s website at www.jazzpharma.com.