WELIREG® (belzutifan) Receives First European Commission Approval for Two Indications

On February 18, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the European Commission (EC) has conditionally approved WELIREG (belzutifan), Merck’s oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, as monotherapy for (Press release, Merck & Co, FEB 18, 2025, View Source [SID1234650338]):

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The treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated, localized renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), and for whom localized procedures are unsuitable;
The treatment of adult patients with advanced clear cell RCC that progressed following two or more lines of therapy that included a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and at least two vascular endothelial growth factor (VEGF) targeted therapies.
The EC approval of these two indications is based on results from the LITESPARK-004 and LITESPARK-005 trials, respectively, and follows the positive recommendation from the Committee for Medicinal Products for Human Use adopted in December 2024. This marks the first approval for WELIREG in the European Union (EU). WELIREG is now approved in over 30 countries for certain adult patients with previously treated advanced RCC and in more than 40 countries for adult patients with certain eligible VHL disease-associated tumors.

"The approval of WELIREG in the EU introduces the first and only systemic treatment option for adult patients with certain VHL disease-associated tumors for whom localized procedures are unsuitable, and offers a new option for adult patients with advanced clear cell renal cell carcinoma that progressed following a PD-1 or PD-L1 inhibitor and at least two VEGF targeted therapies," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "This is an important moment, and we are pleased that WELIREG, a first-in-class HIF-2α inhibitor, can now potentially help these patients in need."

This approval allows marketing of WELIREG for these indications in all 27 EU member states, as well as Iceland, Liechtenstein and Norway. The conditional approval of WELIREG will be valid for one year, subject to yearly renewal, pending additional clinical data from LITESPARK-004 and another ongoing Phase 2 trial of WELIREG in patients with certain VHL disease-associated tumors. Timing for commercial availability of WELIREG in individual EU countries will depend on multiple factors, including the completion of national reimbursement procedures.

Results in Patients With Certain Eligible VHL Disease-associated Tumors (LITESPARK-004)

WELIREG is now the first and only systemic therapy for the treatment of VHL disease-associated tumors in the EU. The approval in adult patients with certain eligible VHL disease-associated tumors is based on objective response rate (ORR) and duration of response (DOR) results from the LITESPARK-004 trial.

WELIREG was approved in the U.S. in August 2021 for the treatment of adult patients with VHL disease who require therapy for associated RCC, CNS hemangioblastomas or pNET not requiring immediate surgery based on the results from LITESPARK-004. In patients with VHL disease-associated RCC (n=61), WELIREG showed an ORR of 49% (95% CI, 36-62) (n=30/61); all responses were partial responses (PR). Median DOR for these patients was not reached, with ongoing responses ranging from 2.8+ to 22+ months; among responders, 56% (n=17/30) maintained a response for at least 12 months. Among these 61 patients, the study also evaluated response rates in other common disease-associated tumors including CNS hemangioblastomas and pNET. In patients with VHL disease-associated CNS hemangioblastomas (n=24) in this trial, WELIREG showed an ORR of 63% (95% CI, 41-81) (n=15/24), with a complete response (CR) rate of 4% (n=1/24) and a PR rate of 58% (n=14/24). Median DOR for these patients was not reached, with ongoing responses ranging from 3.7+ to 22+ months; among responders, 73% (n=11/15) maintained a response for at least 12 months. In patients with VHL disease-associated pNET (n=12) in this trial, WELIREG showed an ORR of 83% (95% CI, 52-98) (n=10/12), with a CR rate of 17% (n=2/12) and a PR rate of 67% (n=8/12). Median DOR for these patients was not reached, with ongoing responses ranging from 11+ to 19+ months; among responders, 50% (n=5/10) maintained a response for at least 12 months.

Results in Certain Patients With Previously Treated Advanced RCC (LITESPARK-005)

The approval in adult patients with advanced clear cell RCC that progressed following two or more lines of therapy, including a PD-1 or PD-L1 inhibitor and at least two VEGF targeted therapies, is based on progression-free survival (PFS) and ORR results from the LITESPARK-005 trial, which was the first trial in advanced RCC to specifically evaluate patients who progressed following these treatments.

WELIREG was approved in the U.S. in December 2023 for the treatment of adult patients with advanced RCC following both a PD-1 or PD-L1 inhibitor and a VEGF-tyrosine kinase inhibitor based on the results from LITESPARK-005. In the trial, WELIREG reduced the risk of disease progression or death by 25% (HR=0.75 [95% CI, 0.63-0.90]; p=0.0008) versus everolimus. Median PFS was 5.6 months (95% CI, 3.9-7.0) for WELIREG versus 5.6 months (95% CI, 4.8-5.8) for everolimus. The ORR for WELIREG was 22% (n=82) (95% CI, 18-27), with a CR rate of 3% (n=10) and a PR rate of 19% (n=72), and the ORR for everolimus was 4% (n=13) (95% CI, 2-6), with no patients achieving a CR and a PR rate of 4% (n=13).

About LITESPARK-004

LITESPARK-004 is an open-label Phase 2 trial (ClinicalTrials.gov, NCT03401788) evaluating WELIREG for the treatment of patients with VHL disease who had at least one measurable solid tumor localized to the kidney and who did not require immediate surgery. The study enrolled 61 patients who received WELIREG (120 mg orally once daily) until disease progression or unacceptable toxicity. The primary endpoint is ORR in VHL disease-associated RCC. Secondary endpoints include, DOR, time to response, PFS, time to surgery and safety. Additionally, this study evaluated response rates in other common VHL disease-associated tumors including pNET and CNS hemangioblastomas.

About LITESPARK-005

LITESPARK-005 is an open-label, randomized, active-controlled Phase 3 trial (ClinicalTrials.gov, NCT04195750) evaluating WELIREG compared to everolimus for the treatment of patients with unresectable, locally advanced or metastatic clear cell RCC that progressed following PD-1 or PD-L1 checkpoint inhibitor and VEGF receptor targeted therapies either in sequence or in combination. The trial enrolled 746 patients who were randomized to receive WELIREG (120 mg orally once daily) or everolimus (10 mg orally once daily). The dual primary endpoints are PFS and overall survival. Secondary endpoints include ORR, DOR and safety.

About von Hippel-Lindau disease

Von Hippel-Lindau disease is a rare genetic disease, which impacts an estimated 200,000 people worldwide and an estimated 10,000 to 15,000 people in Europe. Patients with VHL disease are at risk for recurrent, benign blood vessel tumors as well as some cancerous ones. One of the most commonly occurring tumors is RCC, a form of kidney cancer, which occurs in about 70% of patients with VHL disease.

About renal cell carcinoma

Renal cell carcinoma is by far the most common type of kidney cancer. Clear cell RCC is considered the most common form of RCC, representing about 70% of all cases. In 2020, more than 130,000 new cases of RCC were diagnosed in Europe. Renal cell carcinoma is about twice as common in men than in women. Approximately 30% of patients with kidney cancer are diagnosed at an advanced stage.

About WELIREG (belzutifan) 40 mg tablets, for oral use

Indications in the U.S.

Certain von Hippel-Lindau (VHL) disease-associated tumors

WELIREG (belzutifan) is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

Advanced Renal Cell Carcinoma (RCC)

WELIREG is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) following a programmed death receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI).

Selected Safety Information for WELIREG

Warning: Embryo-Fetal Toxicity

Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception as WELIREG can render some hormonal contraceptives ineffective.

Anemia

WELIREG can cause severe anemia that can require blood transfusion. Monitor for anemia before initiation of, and periodically throughout, treatment. Transfuse patients as clinically indicated. For patients with hemoglobin <8 g/dL, withhold WELIREG until ≥8 g/dL, then resume at the same or reduced dose or permanently discontinue WELIREG, depending on the severity of anemia. For life-threatening anemia or when urgent intervention is indicated, withhold WELIREG until hemoglobin ≥8 g/dL, then resume at a reduced dose or permanently discontinue WELIREG.

In LITESPARK-004 (N=61), decreased hemoglobin occurred in 93% of patients with VHL disease and 7% had Grade 3 events. Median time to onset of anemia was 31 days (range: 1 day to 8.4 months).

The safety of erythropoiesis-stimulating agents (ESAs) for treatment of anemia in patients with VHL disease treated with WELIREG has not been established.

In LITESPARK-005 (n=372), decreased hemoglobin occurred in 88% of patients with advanced RCC and 29% had Grade 3 events. Median time to onset of anemia was 29 days (range: 1 day to 16.6 months). Of the patients with anemia, 22% received transfusions only, 20% received ESAs only, and 12% received both transfusion and ESAs.

Hypoxia

WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization.

Monitor oxygen saturation before initiation of, and periodically throughout, treatment. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same or a reduced dose. For decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or when urgent intervention is indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening or recurrent symptomatic hypoxia, permanently discontinue WELIREG. Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider.

In LITESPARK-004, hypoxia occurred in 1.6% of patients.

In LITESPARK-005, hypoxia occurred in 15% of patients and 10% had Grade 3 events. Of the patients with hypoxia, 69% were treated with oxygen therapy. Median time to onset of hypoxia was 30.5 days (range: 1 day to 21.1 months).

Embryo-Fetal Toxicity

Based on findings in animals, WELIREG can cause fetal harm when administered to a pregnant woman.

Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

Adverse Reactions

In LITESPARK-004, serious adverse reactions occurred in 15% of patients, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each).

WELIREG was permanently discontinued due to adverse reactions in 3.3% of patients for dizziness and opioid overdose (1.6% each).

Dosage interruptions due to an adverse reaction occurred in 39% of patients. Those which required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness.

Dose reductions due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction which required dose reduction was fatigue (7%).

The most common adverse reactions (≥25%), including laboratory abnormalities, that occurred in patients who received WELIREG were decreased hemoglobin (93%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%).

In LITESPARK-005, serious adverse reactions occurred in 38% of patients. The most frequently reported serious adverse reactions were hypoxia (7%), anemia (5%), pneumonia (3.5%), hemorrhage (3%), and pleural effusion (2.2%). Fatal adverse reactions occurred in 3.2% of patients who received WELIREG, including sepsis (0.5%) and hemorrhage (0.5%).

WELIREG was permanently discontinued due to adverse reactions in 6% of patients. Adverse reactions which resulted in permanent discontinuation (≥0.5%) were hypoxia (1.1%) and hemorrhage (0.5%).

Dosage interruptions due to an adverse reaction occurred in 39% of patients. Of the patients who received WELIREG, 28% were 65 to 74 years, and 10% were 75 years and over. Dose interruptions occurred in 48% of patients ≥65 years of age and in 34% of younger patients. Adverse reactions which required dosage interruption in ≥2% of patients were anemia (8%), hypoxia (5%), COVID-19 (4.3%), fatigue (3.2%), and hemorrhage (2.2%).

Dose reductions due to an adverse reaction occurred in 13% of patients. Dose reductions occurred in 18% of patients ≥65 years of age and in 10% of younger patients. The most frequently reported adverse reactions which required dose reduction (≥1.0%) were hypoxia (5%) and anemia (3.2%).

The most common (≥25%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (88%), fatigue (43%), musculoskeletal pain (33%), increased creatinine (34%), decreased lymphocytes (34%), increased alanine aminotransferase (32%), decreased sodium (31%), increased potassium (29%), and increased aspartate aminotransferase (27%).

Drug Interactions

Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended.

Coadministration of WELIREG with CYP3A4 substrates decreases concentrations of CYP3A4 substrates, which may reduce the efficacy of these substrates or lead to therapeutic failures. Avoid coadministration with sensitive CYP3A4 substrates. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information. Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding.

Lactation

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose.

Females and Males of Reproductive Potential

WELIREG can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG.

Use of WELIREG may reduce the efficacy of hormonal contraceptives. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

Based on findings in animals, WELIREG may impair fertility in males and females of reproductive potential and the reversibility of this effect is unknown.

Pediatric Use

Safety and effectiveness of WELIREG in pediatric patients under 18 years of age have not been established.

Lyell Immunopharma Announces Participation in Upcoming Investor Conferences

On February 18, 2025 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage company advancing a pipeline of next-generation CAR T-cell therapies for patients with cancer, reported today that members of its senior management team will present and participate the following upcoming investor conferences (Press release, Lyell Immunopharma, FEB 18, 2025, View Source [SID1234650337]):

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H.C. Wainwright 3rd Annual Cell Therapy Virtual Conference on February 25th at 2:30 pm Eastern Time
TD Cowen’s 45th Annual Health Care Conference on March 3rd at 11:50 am Eastern Time

A live webcast of the presentation can be accessed through the Investors section of the Company’s website at www.lyell.com. Following the live presentation, a replay of the webcast will be available on the Company’s website.

Kiromic BioPharma Reports Patient 4 in Deltacel-01 Clinical Trial Reaches 10-Month Progression-Free Survival

On February 18, 2025 Kiromic BioPharma, Inc. (OTCQB: KRBP) ("Kiromic" or the "Company") reported continued favorable efficacy results from the 10-month follow-up visit for the fourth patient enrolled in its Deltacel-01 Phase 1 clinical trial and provides an enrollment update (Press release, Kiromic, FEB 18, 2025, View Source [SID1234650336]). This trial is evaluating Deltacel (KB-GDT-01), the Company’s allogeneic, off-the-shelf, Gamma Delta T-cell (GDT) therapy, in patients with stage 4 metastatic or locally-advanced non-small cell lung cancer (NSCLC) who have failed to respond to standard therapies.

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The fourth patient in Deltacel-01 demonstrated a partial response (defined as a 30% or greater decrease in the size of the tumor) at the eight-month follow-up visit and continued without any evidence of disease progression as of the 10-month follow-up visit, thereby extending progression-free survival (PFS) to 10 months.

"We are very pleased that as of January 2025 Patient 4 had no evidence of disease progression since the partial response registered in November 2024, with a PFS of 10 months reinforcing our view that Deltacel may offer a transformative treatment option for people with advanced solid tumors," said Pietro Bersani, Chief Executive Officer of Kiromic BioPharma. "Our team remains committed to advancing the Deltacel-01 clinical program, and we look forward to building upon these encouraging results as we expand the trial to additional participants."

Additionally, Kiromic reports that two subjects are undergoing screening and are scheduled to start treatment at Texas Oncology in Tyler, Texas, in late February and early March, respectively.

About Deltacel-01

In Kiromic’s open-label Phase 1 clinical trial, titled "Phase 1 Trial Evaluating the Safety and Tolerability of Gamma Delta T Cell Infusions in Combination With Low Dose Radiotherapy in Subjects With Stage 4 Metastatic Non-Small Cell Lung Cancer" (NCT06069570), patients with advanced NSCLC receive three intravenous infusions of Deltacel with six courses of low-dose, localized radiation over a 31-day period. The primary objective of Deltacel-01 is to evaluate safety, while secondary measurements include objective response, progression-free survival, overall survival, time to progression, time to treatment response and disease control rates.

About Deltacel

Deltacel (KB-GDT-01) is an investigational gamma delta T-cell (GDT) therapy currently in the Deltacel-01 Phase 1 trial for the treatment of stage 4 metastatic NSCLC. An allogeneic product consisting of unmodified, donor-derived gamma delta T cells, Deltacel is the leading candidate in Kiromic’s GDT platform. Deltacel is designed to exploit the natural potency of GDT cells to target solid cancers, with an initial clinical focus on NSCLC, which represents about 80% to 85% of all lung cancer cases. Data from two preclinical studies demonstrated Deltacel’s favorable safety and efficacy profile when it was combined with low-dose radiation.

HALOZYME REPORTS FULL YEAR 2024 RECORD REVENUE of $1.015 BILLION AND EXCEEDS ITS FINANCIAL GUIDANCE FOR ROYALTY REVENUE, ADJUSTED EBITDA and NON-GAAP DILUTED EPS

On February 18, 2025 Halozyme Therapeutics, Inc. (NASDAQ: HALO) ("Halozyme" or the "Company") reported its financial and operating results for the fourth quarter and full year ended December 31, 2024, provided an update on its recent corporate activities and reiterated its 2025 financial guidance (Press release, Halozyme, FEB 18, 2025, View Source [SID1234650335]).

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"I am excited to announce that the significant growth we achieved throughout the year culminated in two important milestones for the Company: achievement of more than $1 billion in total revenue and reaching a cumulative one million patients with our ENHANZE drug delivery technology. Our 2024 royalty revenue exceeded guidance driven by continued strong growth of DARZALEX SC and Phesgo, with modest initial contribution from VYVGART Hytrulo resulting from growing adoption and use primarily from its first indication for generalized myasthenia gravis. These three products will continue to drive our 2025 royalty revenues, with VYVGART Hytrulo becoming the largest dollar growth contributor in 2025," said Dr. Helen Torley, president and chief executive officer of Halozyme.

"I am also pleased that we achieved four additional, significant ENHANZE regulatory product and indication approvals in the U.S. and EU in 2024 for VYVGART Hytrulo for CIDP, Tecentriq Hybreza, Ocrevus Zunovo and Opdivo Qvantiq, positioning Halozyme for strong continued growth, post 2025, once coverage reimbursement and access are fully established," said Dr. Torley.

"Our leadership position in rapid subcutaneous drug delivery and long-term growth was further fortified with five new ENHANZE nominations from argenx and ViiV and an extension of our ENHANZE patent in Europe out to 2029, with a similar patent submitted in the U.S. Our 2025 guidance reflects our confidence in continuing robust total revenue, royalty revenue, adjusted EBITDA and non-GAAP EPS growth," Dr. Torley concluded.

Fourth Quarter and Recent Corporate Highlights:
•Reiterating 2025 financial guidance previously announced on January 8, 2025 including total revenue of $1,150 million to $1,225 million, representing year-over-year growth of 13% to 21%, adjusted EBITDA of $755 million to $805 million, representing year-over-year growth of 19% to 27% and non-GAAP diluted earnings per share of $4.95 to $5.35, representing year-over-year growth of 17% to 26%.
•In December 2024, Halozyme entered into an Accelerated Share Repurchase agreement to repurchase $250.0 million of its common stock under the $750 million approved program from February 2024.

Fourth Quarter and Recent Partner Highlights:
•In February 2025, Janssen-Cilag International NV, a Johnson & Johnson company, received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency recommending an extension of marketing authorization for a subcutaneous ("SC") formulation of RYBREVANT (amivantamab) with ENHANZE in combination with LAZCLUZE (lazertinib) for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, and as a monotherapy for the treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy.
•In December 2024, Bristol Myers Squibb announced the U.S Food and Drug Administration ("FDA") approved Opdivo Qvantig (nivolumab and hyaluronidase-nvhy) with ENHANZE for SC use in most previously approved adult, solid tumor IV Opdivo (nivolumab) indications resulting in the recognition of a $20.0 million milestone payment, and in January 2025, Opdivo Qvantig was made available to patients.
•In December 2024, argenx announced the Ministry of Health, Labour and Welfare ("MHLW") in Japan approved VYVDURA for the treatment of patients with chronic inflammatory demyelinating polyneuropathy ("CIDP").
•In December 2024, Takeda announced the MHLW in Japan approved HYQVIA with ENHANZE for patients with agammaglobulinemia or hypogammaglobulinemia disorders characterized by very low or absent levels of antibodies and an increased risk of serious recurring infection caused by primary immunodeficiency or secondary immunodeficiency.
•In November 2024, Zai Lab Limited (argenx commercial partner for China) announced the National Medical Products Administration approved VYVGART Hytrulo for the treatment of patients with CIDP.
•In November 2024, Janssen announced the submission of regulatory applications to the FDA and European Medicines Agency ("EMA") seeking approval of a new indication for DARZALEX FASPRO in the U.S. and DARZALEX SC in the EU as a monotherapy for the treatment of adult patients with high-risk smoldering multiple myeloma.
•In October 2024, argenx initiated two studies evaluating VYVGART Hytrulo with ENHANZE, a Phase 3 study for adult patients with ocular myasthenia gravis and a Phase 2 study for kidney transplant recipients with antibody mediated rejection.

•In October 2024, Janssen announced the European Commission approved DARZALEX SC for the treatment of patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant in combination with bortezomib, lenalidomide and dexamethasone.

Fourth Quarter and Full Year 2024 Financial Highlights:
•Revenue was $298.0 million, compared to $230.0 million in the fourth quarter of 2023. The 30% year-over-year increase was primarily driven by royalty revenue growth and higher revenues under collaborative agreements mainly due to the timing of milestones achieved. Revenue for the quarter included $170.4 million in royalties, an increase of 40% compared to $122.1 million in the fourth quarter of 2023, primarily attributable to increases in revenue of DARZALEX SC, VYVGART Hytrulo and Phesgo.
Total revenue for the full year was $1,015.3 million, compared to $829.3 million in 2023, representing 22% year-over-year growth. The increase was primarily driven by royalty revenue growth, higher revenues under collaborative agreements mainly due to the timing of milestones achieved and higher sales of our proprietary products.
•Cost of sales was $42.1 million, compared to $52.3 million in the fourth quarter of 2023. The decrease was primarily due to lower bulk rHuPH20 sales.
Cost of sales for the full year was $159.4 million, compared to $192.4 million in 2023. The decrease was primarily due to lower bulk rHuPH20 and device sales, partially offset by higher proprietary product sales.
•Amortization of intangibles expense was $17.8 million, compared to $17.8 million in the fourth quarter of 2023.
Amortization of intangibles expense for the full year was $71.0 million, compared to $73.8 million in 2023. The decrease was primarily due to an impairment charge of $2.5 million recognized in the prior year to fully impair the TLANDO product rights intangible asset.
•Research and development expense was $20.4 million, compared to $21.3 million in the fourth quarter of 2023.
Research and development expense for the full year was $79.0 million, compared to $76.4 million in 2023. The increase was primarily due to planned investments in ENHANZE related to the development of our new high-yield rHuPH20 manufacturing processes.
•Selling, general and administrative expense was $42.2 million, compared to $37.6 million in the fourth quarter of 2023. The increase was primarily due to increased compensation expense and consulting and professional service fees.
Selling, general and administrative expense for the full year was $154.3 million, compared to $149.2 million in 2023. The increase was primarily due to increased compensation expense and consulting and professional service fees, partially offset by planned reductions in commercial marketing expense.
•Operating income was $175.5 million, compared to $101.0 million in the fourth quarter of 2023.
Operating income for the full year was $551.5 million, compared to $337.6 million in 2023.
•Net income was $137.0 million, compared to $85.4 million in the fourth quarter of 2023.
Net income for the full year was $444.1 million, compared to $281.6 million in 2023.
•EBITDA was $195.8 million, compared to $121.7 million in the fourth quarter of 2023. Adjusted EBITDA was $195.8 million, compared to $121.7 million in the fourth quarter of 2023.1
EBITDA for the full year was $632.2 million, compared to EBITDA of $435.6 million in 2023. Adjusted EBITDA for the full year was $632.2 million, compared to $426.2 million in 2023.

•GAAP diluted earnings per share was $1.06, compared to $0.65 in the fourth quarter of 2023. Non-GAAP diluted earnings per share was $1.26, compared to $0.82 in the fourth quarter of 2023.1
GAAP diluted earnings per share for the full year was $3.43, compared to $2.10 in 2023. Non-GAAP diluted earnings per share for the full year was $4.23, compared to $2.77 in 2023.1
•Cash, cash equivalents and marketable securities were $596.1 million on December 31, 2024, compared to $336.0 million on December 31, 2023. The increase was primarily a result of cash generated from operations.

Financial Outlook for 2025
The Company is reiterating its financial guidance for 2025, which was initially provided on January 8, 2025. For the full year 2025, the Company expects:

•Total revenue of $1,150 million to $1,225 million, representing growth of 13% to 21% over 2024 total revenue, primarily driven by increases in royalty revenue and product sales from XYOSTED.
•Revenue from royalties of $725 million to $750 million, representing growth of 27% to 31% over 2024.
•Adjusted EBITDA of $755 million to $805 million, representing growth of 19% to 27% over 2024.
•Non-GAAP diluted earnings per share of $4.95 to $5.35, representing growth of 17% to 26% over 2024. The Company’s earnings per share guidance does not consider the impact of potential future share repurchases.

Table 1. 2025 Financial Guidance


Guidance Range
Total Revenue
$1,150 to $1,225 million
Royalty Revenue
$725 to $750 million
Adjusted EBITDA
$755 to $805 million
Non-GAAP Diluted EPS
$4.95 to $5.35

Lilly to participate in TD Cowen’s 45th Annual Health Care Conference

On February 18, 2025 Eli Lilly and Company (NYSE: LLY) reported it will participate in TD Cowen’s 45th Annual Health Care Conference on March 4, 2025. Jake Van Naarden, executive vice president and president, Lilly Oncology, will take part in a fireside chat at 1:50 p.m., Eastern time (Press release, Eli Lilly, FEB 18, 2025, View Source [SID1234650334]).

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Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A live audio webcast will be available on the "Webcasts & Presentations" section of Lilly’s investor website at View Source A replay of the presentation will be available on this same website for approximately 90 days.