On March 4, 2025 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel radioimmunotherapy and antibody-based therapeutic products for the treatment of cancer, reported financial results for the fourth quarter and full year ended December 31, 2024 (Press release, Y-mAbs Therapeutics, MAR 4, 2025, View Source [SID1234650887]).

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"We delivered on the strategic priorities we set out to achieve in 2024 across our business," said Michael Rossi, President and Chief Executive Officer. "In our DANYELZA business, we saw solid ex-U.S. growth in 2024 from our partners. In the U.S., while DANYELZA revenues stabilized in the face of increased competition from new market entrants and clinical trial activity, we remain committed to further penetrating high-volume centers and reaching more patients with high-risk relapsed/refractory neuroblastoma. In our Radiopharmaceutical business, we demonstrated the tolerability and validity of our SADA PRIT platform pre-targeting approach with the preliminary readout from Part A of our GD2-SADA Phase 1 trial, Trial 1001, in solid tumors, and we look forward to providing a complete data readout in the second quarter of this year. With our business realignment announced at the beginning of 2025, we expect to be in position to enhance our ability to execute on our business goals to drive future growth with DANYELZA while accelerating the preclinical and clinical advancement of our SADA PRIT platform and programs."

Recent Corporate Highlights

● On January 10, 2025, Y-mAbs announced the internal realignment and establishment of two business units: DANYELZA and Radiopharmaceuticals. The business realignment is designed to support the optimization of internal resources and provide flexibility and agility to advance the Company’s novel Self-Assembly DisAssembly Pre-targeted Technology platform (SADA PRIT) programs through clinical development while simultaneously driving commercial growth of DANYELZA.
● In conjunction with the business realignment, Y-mAbs appointed Doug Gentilcore as Senior Vice President, Head of DANYELZA Business Unit. Mr. Gentilcore has over two decades of strategic leadership experience in the pharmaceutical industry.
● Y-mAbs presented translational pharmacokinetics data of GD2-SADA at the Society of Nuclear Medicine & Molecular Imaging (SNMMI) Mid-Winter and American College of Nuclear Medicine (ACNM) Annual Meeting on January 31, 2025. The poster titled "Preclinical and Translational Pharmacokinetics of GD2-SADA, a Self-Assembling and Disassembling (SADA) Bispecific Fusion Protein for Pre-targeted Radioimmunotherapy (PRIT)" characterizes the plasma levels of GD2-SADA in animal models over time and a range of doses, while also presenting the concentration- and time-dependent equilibrium between GD2-SADA tetramers and monomers in vitro. Incorporated within translational PK simulations, the data have provided insights into GD2-SADA tumor exposure and plasma elimination, key parameters for minimizing systemic exposure to 177Lutetium-DOTA.
● Interim data from a Phase 2 clinical trial evaluating naxitamab with granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with relapsed/refractory high-risk neuroblastoma in the journal Nature Communications. The article, titled "The anti-GD2 monoclonal antibody naxitamab plus GM-CSF for relapsed or refractory high-risk neuroblastoma: a phase 2 clinical trial," details the results of a single-arm, global Phase 2 trial (Trial 201, NCT03363373) of patients with relapsed/refractory high-risk neuroblastoma and residual disease in the bone/bone marrow who received naxitamab on days 1, 3, and 5 (3 mg/kg/day) with GM-CSF (days -4 to 5) every 4 weeks, until a complete response (CR) or partial response (PR) was achieved, followed by 5 additional cycles every 4 weeks. Overall, naxitamab demonstrated statistically significant efficacy with a manageable safety profile.
Fourth Quarter 2024 Key Highlights

● Y-mAbs entered into an exclusive license and distribution agreement with Nobelpharma Co. Ltd. for the development and commercialization of DANYELZA in Japan. Y-mAbs received an upfront payment of $2.0 million in the fourth quarter of 2024. In addition, Y-mAbs is entitled to receive up to $31.0 million in regulatory-based and sales-based milestone payments in addition to royalty payments on commercial sales of DANYELZA by Nobelpharma, if successfully approved and commercialized in Japan.
● Continued commercial success with the named patient program for DANYELZA in Turkey with partner INPHARMUS (formerly named TRPharm İlaç Sanayi Ticaret A.Ş. and TRPharm FZ-LLC).
● Y-mAbs received notification of the accepted patent extension for DANYELZA, US 9,315,585, through February 2034.

Financial Results

Revenues

Total revenues for the quarter ended December 31, 2024 were $26.5 million, which was a 13% increase over the $23.4 million of total revenues for the quarter ended December 31, 2023, primarily driven by a $2.0 million increase in license revenue, and a $1.1 million increase in net product revenues.

Total revenues for the year ended December 31, 2024 were $87.7 million, a 3% increase over the total revenues for the year ended December 31, 2023 of $84.8 million. The $2.9 million increase was driven by a $2.0 million increase in license revenue, and a $0.9 million increase in net product revenues.

The Company’s U.S. DANYELZA net product revenues for the quarter and year ended December 31, 2024 were $16.8 and $66.0 million, representing decreases of 12% and 3%, respectively, from the same periods in 2023. The decline in the U.S. DANYELZA net product revenues was driven by an unfavorable price mix for the quarter and year ended December 31, 2024, compared to 2023. The decline for the quarter ended December 31, 2024, was partially offset by slightly increased volume, compared to 2023.

The Company’s international DANYELZA net product revenues for the quarter and year ended December 31, 2024 were $7.7 million and $19.2 million, representing increases of 78% and 16%, respectively, from the same periods in 2023. The increase in the international DANYELZA net product revenues was driven by the named patient program launch in Western Asia in 2024 and increased net product sales in the Eastern Asia, where our distribution partner purchased inventory in 2024 to avoid potential supply disruption in advance of a planned post-marketing labeling change in 2025, and Latin America regions, partially offset by decreased sales in Western Europe.

As of December 31, 2024, Y-mAbs had delivered DANYELZA to 69 centers across the U.S. since initial launch, with 11 new accounts added in the U.S. in 2024. During the quarter ended December 31, 2024, approximately 64% of the vials sold in the U.S. were sold outside of Memorial Sloan Kettering Cancer Center ("MSK"), compared to 65% in the third quarter ended September 30, 2024.

During the quarter and year ended December 31, 2024, the Company recognized license revenue of $2.0 million upon the execution of a license agreement with Nobelpharma in October 2024. The Company had license revenues totaling $2.5 million for the year ended December 31, 2024, which included license revenue from the Latin America distribution partner, Adium, related to price approval for DANYELZA in Brazil from the Brazilian Medicines Market Regulation Chamber, and from Nobelpharma, as noted above. The Company did not have any license revenue for the quarter ended December 31, 2023. The Company had license revenues of $0.5 million for the year ended December 31, 2023 from Adium, recognized upon the September 2023 achievement of marketing authorization for DANYELZA in Mexico.

Cost of Goods Sold

Cost of goods sold were $7.6 million and $2.0 million for the quarters ended December 31, 2024 and 2023, respectively, and were $15.0 million and $11.4 million for the years ended December 31, 2024 and 2023, respectively. Cost of goods sold included $0.6 million inventory write-off for the quarter and year ended December 31, 2024. The Company did not have any inventory write-off for the quarter ended December 31, 2023, and the Company had $0.8 million inventory write-downs in the year ended December 31, 2023.

Gross Profit

Gross profit was $18.9 million and $21.3 million for the quarters ended December 31, 2024 and 2023, respectively. Gross profit was $72.7 million and $73.5 million for the years ended December 31, 2024 and 2023, respectively. The decrease in gross profit was driven by the unfavorable price mix in connection with increased net product revenue from Eastern Asia, which generally has lower gross margins.

Operating Costs and Expenses

Research and Development

Research and development expenses were $12.2 million and $13.4 million for the quarters ended December 31, 2024 and 2023, respectively. The decrease in research and development expenses was primarily due to a $1.8 million decrease in outsourced manufacturing, a $0.4 million reduction of future milestone payments as the Company entered into an amendment with MSK to return the licensed patent rights related to omburtamab, and related drug substance inventory and regulatory work products, partially offset by a $1.0 million expense related to severance benefits and stock-based compensation charges associated with our business realignment.

Research and development expenses were $49.0 million for the year ended December 31, 2024, a decrease of $5.2 million when compared with the same period in 2023. The decrease in research and development expenses was primarily attributable to the recognition of $4.1 million of milestone and license acquisition costs related to the Company’s SADA license agreement during the year ended December 31, 2023, as certain time-based clinical milestones within the agreement were determined to be probable based on the availability of necessary data and the assessment of clinical progress in the third quarter of 2023.

Selling, General, and Administrative

Selling, general, and administrative expenses were $12.4 million and $11.1 million for the quarters ended December 31, 2024 and 2023, respectively. The $1.3 million increase in the selling, general and administrative expenses was primarily attributable to a $0.8 million increase in personnel cost, inclusive of stock-based compensation, and a $0.6 million expense related to severance benefits and stock-based compensation charges associated with our business realignment.

For the year ended December 31, 2024, selling, general, and administrative expenses were $54.6 million, an increase of $9.7 million compared with the same period in 2023. The increase was primarily attributable to a net impact of $3.8 million related to legal settlements, a $1.2 million charge related to separation and consulting agreements with a former executive and a $2.2 million increase in personnel cost, inclusive of stock-based compensation.

Interest and Other (Loss)/Income

The Company experienced interest and other loss of $1.6 million for the quarter ended December 31, 2024, as compared to interest and other income of $2.4 million for the quarter ended December 31, 2023. The decrease of $4.0 million was primarily due to a $3.7 million decrease in foreign currency transactional gains in the three months ended December 31, 2024, and a $0.3 million decrease in interest earned on the Company’s cash and cash equivalents.

For the years ended December 31, 2024 and 2023, the interest and other income was $1.4 and $4.8 million, respectively. The decrease of $3.4 million was primarily due to $2.6 million decrease of foreign currency transactional gains, partially offset by a $0.7 million decrease in interest earned on the Company’s cash and cash equivalents.

Net Loss

Y-mAbs reported a net loss for the quarter ended December 31, 2024, of $6.8 million, or ($0.15) per basic and diluted share, compared to a net loss of $1.0 million, or ($0.02) per basic and diluted share, for the quarter ended December 31, 2023. For the year ended December 31, 2024, the Company reported a net loss of $29.7 million, or ($0.67) per basic and diluted share, as compared to net loss of $21.4 million, or ($0.49) per basic and diluted share, for the year ended December 31, 2023. The increase in net loss for the quarter and year ended December 31, 2024 was primarily driven by increased operating expenses and decreased foreign currency transactional gains, partially offset by increased total revenues.

Cash and Cash Equivalents

As of December 31, 2024, Y-mAbs had approximately $67.2 million in cash and cash equivalents. Total annual cash investment in 2024 was $11.4 million, which was favorable relative to the Company’s corporate guidance for the full year 2024, which was between $15 million and $20 million. The Company continues its efforts to be capital efficient in its operations.

2025 Financial Guidance

Management announces its guidance for the full year 2025:

● Anticipated Total Revenues expected to be between $75 million and $90 million;
● Anticipated Total Operating Costs and Expenses, excluding cost of goods sold, expected to be between $116 million and $121 million (Total Operating Costs and Expenses including cost of goods sold is anticipated to be between $129 million and $134 million);
● Anticipated Total Annual Cash Investment expected to be between $25 million and $30 million; and
● Cash and Cash Equivalents anticipated to be sufficient to fund operations as currently planned into 2027.
Management announces its guidance for the first quarter 2025:

● Anticipated Total Revenues expected to be between $18 million and $21 million.
Webcast and Conference Call

Y-mAbs will host a conference call on Tuesday, March 4, 2025, at 8:00 a.m. ET. To participate in the live conference call, register here:

https://register.vevent.com/register/BIc0434de7d34443d1a7e4c7635d2c9faa

To listen to the live webcast, please use this link. Prior to the call and webcast, a slide presentation pertaining to the Company’s quarterly earnings will be made available on the Investor Relations section of the Y-mAbs website, www.ymabs.com, shortly before the call begins.

On March 4, 2025 Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel product candidates for immuno-inflammatory diseases, reported that the Company will participate in two upcoming healthcare conferences in March (Press release, Aclaris Therapeutics, MAR 4, 2025, View Source [SID1234650871]).

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On Tuesday March 11, 2025, at 3:00 PM EDT, Aclaris’ Chief Executive Officer Dr. Neal Walker and other members of Aclaris’ senior leadership team will participate in a fireside chat during the Leerink Partners Global Healthcare Conference in Miami, Florida.

On Thursday March 27, 2025, at 9:00 AM EDT, Dr. Walker and other members of Aclaris’ senior leadership team will participate in a virtual fireside chat during the H.C. Wainwright 3rd Annual Autoimmune & Inflammatory Disease

Virtual Conference
A live and archived webcast of both events will be accessible on the Events page of View Source The webcasts will be available on the Aclaris website for at least 30 days.

On March 4, 2025 AC Immune SA (NASDAQ: ACIU), a clinical-stage biopharmaceutical company pioneering precision medicine for neurodegenerative diseases, reported that the company’s management will participate in the following investor conferences in March (Press release, AC Immune, MAR 4, 2025, View Source [SID1234650888]):

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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

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Leerink Partners 2025 Global Healthcare Conference,
Management will participate in investor meetings on March 10, 2025

Barclays 27th Annual Global Healthcare Conference,
Management will participate in investor meetings on March 11, 2025

Please contact your Leerink or Barclays representative or AC Immune to request a one-on-one meeting with AC Immune’s management team at the conferences.

On March 4, 2025 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in cellular metabolism and PK activation pioneering therapies for rare diseases, reported that its management team is scheduled to present at the following conferences (Press release, Agios Pharmaceuticals, MAR 4, 2025, View Source [SID1234650872]):

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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

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Leerink Global Healthcare Conference 2025: Fireside chat on Tuesday, March 11, 2025, at 10:50 a.m. ET
Barclays 27th Annual Global Healthcare Conference: Fireside chat on Wednesday, March 12, 2025, at 12:30 p.m. ET

The live webcast for each event will be accessible on the Investors section of the company’s website (www.agios.com) under the "Events & Presentations" tab. Replays of the webcasts will be archived on the company’s website for at least two weeks following the presentation.

On March 4, 2025 BeiGene, Ltd. (NASDAQ: ONC; HKEX: 06160; SSE: 688235), a global oncology company that intends to change its name to BeOne Medicines Ltd., reported the U.S. Food and Drug Administration (FDA) has approved TEVIMBRA (tislelizumab-jsgr), in combination with platinum-containing chemotherapy, for the first-line treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥1) (Press release, BeiGene, MAR 4, 2025, View Source [SID1234650874]).

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"The approval of TEVIMBRA in combination with chemotherapy for adult patients with ESCC expands first-line treatment options for patients with this disease," said Dr. Nataliya Uboha, Associate Professor, University of Wisconsin, Carbone Cancer Center. "There is a critical need for effective treatments of ESCC, and TEVIMBRA has been shown to improve outcomes in this patient population."

The additional indication is based on results from BeiGene’s RATIONALE-306 (NCT03783442), a randomized, placebo-controlled, double-blind, global Phase 3 study to evaluate the efficacy and safety of TEVIMBRA in combination with platinum-containing chemotherapy as a first-line treatment in adult patients (n=649) with unresectable, locally advanced recurrent or metastatic ESCC. The study met its primary endpoint and demonstrated a statistically significant improvement in overall survival (OS) for adult patients randomized to TEVIMBRA in combination with chemotherapy compared to placebo in combination with chemotherapy. Exploratory analyses indicated that the improvement in the intent-to-treat (ITT) population was primarily attributed to the results observed in the subgroup of patients with PD-L1 ≥1. Analysis of OS in the PD-L1 positive (≥1) population (n=481) showed a median OS of 16.8 months for patients treated with TEVIMBRA plus chemotherapy compared to 9.6 months for patients treated with placebo plus chemotherapy (HR: 0.66, [95% CI: 0.53, 0.82]), resulting in a 34% reduction in the risk of death. These results represent an unprecedented improvement in OS in first-line ESCC patients.

"Today’s approval, our third from the FDA in less than a year, reflects our dedication to advancing innovative therapies and addressing critical needs in cancer care," said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "FDA approval of TEVIMBRA for the first-line treatment of advanced esophageal squamous cell carcinoma marks a significant step forward in tackling the unmet needs in this challenging disease area. We are grateful to the patients, clinicians, and researchers whose commitment and courage have made this progress possible."

The safety of TEVIMBRA in combination with chemotherapy was evaluated in the same global clinical trial, RATIONALE-306. The most frequent serious adverse reactions (≥2%) were pneumonia, dysphagia, diarrhea, fatigue, and esophageal stenosis. The most common (≥20%) adverse reactions were anemia, fatigue, decreased appetite, nausea, constipation, decreased weight, diarrhea, peripheral sensory neuropathy, vomiting, and stomatitis.

TEVIMBRA is also approved in the U.S. as monotherapy for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor and in combination with chemotherapy for the first-line treatment of adults with gastric and gastroesophageal junction (G/GEJ) cancers.

The Company recently announced its intent to change its name to BeOne Medicines Ltd., reaffirming its commitment to develop innovative medicines to eliminate cancer by partnering with the global community to serve as many patients as possible.

About Esophageal Squamous Cell Carcinoma (ESCC)

Globally, esophageal cancer is the sixth most common cause of cancer-related deaths, and ESCC is the most common histologic subtype, accounting for nearly 90% of esophageal cancers. An estimated 957,000 new esophageal cancer cases are projected in 2040, an increase of nearly 60% from 2020, underscoring the need for additional effective treatments.1 Esophageal cancer is a rapidly fatal disease, and more than two-thirds of patients have advanced or metastatic disease at the time of diagnosis, with an expected five-year survival rate of less than 6% for those with distant metastases.2

About TEVIMBRA (tislelizumab-jsgr)

TEVIMBRA is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping the body’s immune cells detect and fight tumors.

TEVIMBRA is the foundational asset of BeiGene’s solid tumor portfolio and has shown potential across multiple tumor types and disease settings. The global TEVIMBRA clinical development program includes almost 14,000 patients enrolled to date in 34 countries and regions across 66 trials, including 20 registration-enabling studies. TEVIMBRA is approved in more than 42 countries, and more than 1.3 million patients have been treated globally.

U.S. Indication and Important Safety Information for TEVIMBRA (tislelizumab-jsgr) injection

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Severe and Fatal Immune-Mediated Adverse Reactions

TEVIMBRA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated reactions.

Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue TEVIMBRA depending on severity. In general, if TEVIMBRA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids.

Immune-Mediated Pneumonitis

TEVIMBRA can cause immune-mediated pneumonitis, which can be fatal. In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation.

Immune-mediated pneumonitis occurred in 4.9% (96/1972) of patients receiving TEVIMBRA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (1.6%) and Grade 2 (1.9%) adverse reactions. Pneumonitis led to permanent discontinuation of TEVIMBRA in 38 (1.9%) patients and withholding of TEVIMBRA in 32 (1.6%) patients.

Seventy-four (77.1%) of the 96 patients received systemic corticosteroids. Sixty-five (67.7%) of the 96 patients received high-dose systemic corticosteroids. Immune-mediated pneumonitis resolved in 50% of the 96 patients. Of the 32 patients in whom TEVIMBRA was withheld for pneumonitis, 20 (62.5%) reinitiated TEVIMBRA after symptom improvement; of these, 2 (10%) patients had recurrence of pneumonitis.

Immune-Mediated Colitis

TEVIMBRA can cause immune-mediated colitis, which can be fatal. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1 blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

Immune-mediated colitis occurred in 0.8% (16/1972) of patients receiving TEVIMBRA, including Grade 3 (0.3%) and Grade 2 (0.4%) adverse reactions. Colitis led to permanent discontinuation of TEVIMBRA in 4 (0.2%) patients and withholding of TEVIMBRA in 5 (0.3%) patients. Twelve (75%) of the 16 patients received systemic corticosteroids. Eight (50%) of the 16 patients received high-dose systemic corticosteroids. Two (12.5%) of the 16 patients received immunosuppressive treatment. Immune-mediated colitis resolved in 93.8% of the 16 patients. All 5 patients in whom TEVIMBRA was withheld for colitis reinitiated TEVIMBRA after symptom improvement; of these, none of the patients had recurrence of colitis.

Immune-Mediated Hepatitis

TEVIMBRA can cause immune-mediated hepatitis, which can be fatal.

Immune-mediated hepatitis occurred in 1.2% (24/1972) of patients receiving TEVIMBRA, including fatal (0.1%), Grade 4 (0.2%), Grade 3 (0.5%) and Grade 2 (0.4%) adverse reactions. Immune-mediated hepatitis led to permanent discontinuation in 3 (0.2%) patients and withholding of TEVIMBRA in 13 (0.7%) patients. Eighteen (75%) of the 24 patients received systemic corticosteroids. Thirteen (54.2%) of the 24 patients received high-dose systemic corticosteroids. Two patients (8.3%) of the 24 patients received immunosuppressive treatment. Immune-mediated hepatitis resolved in 70.8% of the 24 patients. Of the 13 patients in whom TEVIMBRA was withheld for hepatitis, 7 (53.8%) reinitiated TEVIMBRA after symptom improvement; of these, none of the patients had recurrence of hepatitis.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

TEVIMBRA can cause immune-mediated adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold TEVIMBRA depending on severity.

Immune-mediated adrenal insufficiency occurred in 0.4% (8/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%), Grade 3 (0.1%) and Grade 2 (0.3%) adverse reactions. Adrenal insufficiency did not lead to permanent discontinuation of TEVIMBRA. TEVIMBRA was withheld in 7 (0.4%) patients. All 8 patients received systemic corticosteroids. Three (37.5%) of the 8 patients received high-dose systemic corticosteroids. Adrenal insufficiency resolved in 25% of the 8 patients. Of the 7 patients in whom TEVIMBRA was withheld for adrenal insufficiency, 5 (71.4%) reinitiated TEVIMBRA after symptom improvement; of these, none of the patients had recurrence of adrenal insufficiency.

Hypophysitis

TEVIMBRA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity.

Hypophysitis/hypopituitarism occurred in 0.2% (4/1972) of patients receiving TEVIMBRA, including a Grade 2 (0.2%) adverse reaction. No TEVIMBRA treatment discontinuation was required, while treatment was withheld in 1 (0.1%) patient. Three (75%) of the 4 patients received systemic corticosteroids. One (25%) of the 4 patients received high-dose systemic corticosteroids. Hypophysitis/hypopituitarism did not resolve in the 4 patients. For the 1 patient where TEVIMBRA was withheld for hypophysitis/hypopituitarism, there was no recurrence of hypophysitis/hypopituitarism.

Thyroid Disorders

TEVIMBRA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity.

Thyroiditis: Immune-mediated thyroiditis occurred in 1.2% (24/1972) of patients receiving TEVIMBRA, including Grade 2 (0.5%) adverse reactions. Thyroiditis did not lead to permanent discontinuation of TEVIMBRA. TEVIMBRA was withheld in 3 (0.2%) patients. Two (8.3%) of the 24 patients received systemic corticosteroids. Thyroiditis resolved in 41.7% of the 24 patients. All three patients in whom TEVIMBRA was withheld for thyroiditis reinitiated TEVIMBRA after symptom improvement; of these, none of the patients had recurrence of thyroiditis.

Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 4.8% (95/1972) of patients receiving TEVIMBRA, including Grade 3 (0.1%) and Grade 2 (0.9%) adverse reactions. Hyperthyroidism led to the permanent discontinuation of TEVIMBRA in 1 (0.1%) patient and withholding of TEVIMBRA in 4 (0.2%) patients. One (1.1%) of the 95 patients received systemic corticosteroids. Hyperthyroidism resolved in 75.8% of the 95 patients. Of the 4 patients in whom TEVIMBRA was withheld for hyperthyroidism, 3 (75%) reinitiated TEVIMBRA after symptom improvement; of these, none of the patients had recurrence of hyperthyroidism.

Hypothyroidism: Immune-mediated hypothyroidism occurred in 12.7% (250/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%) and Grade 2 (6.8%) adverse reactions. TEVIMBRA was not permanently discontinued in any patient, while treatment was withheld in 7 (0.4%) patients. Two (0.8%) of the 250 patients received systemic corticosteroids and 158 patients (63.2%) received hormone replacement therapy. Hypothyroidism resolved in 31.6% of the 250 patients. The majority (51.6%) of patients with hypothyroidism required long-term thyroid hormone replacement. Of the 7 patients in whom TEVIMBRA was withheld for hypothyroidism, 6 (85.7%) reinitiated TEVIMBRA after symptom improvement; of these, none of the patients had recurrence of hypothyroidism.

Type 1 Diabetes Mellitus, which can present with Diabetic Ketoacidosis

Diabetes mellitus has been reported with PD-1/PD-L1 blocking antibodies. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity.

Diabetes mellitus occurred in 0.9% (18/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%), Grade 3 (0.4%) and Grade 2 (0.4%) adverse reactions. TEVIMBRA was permanently discontinued in 3 (0.2%) patients and TEVIMBRA treatment was withheld in 3 (0.2%) patients. Twelve (66.7%) patients received insulin therapy for diabetes mellitus. Diabetes mellitus resolved in 27.8% of the 18 patients. Of the 3 patients in whom TEVIMBRA was withheld for diabetes mellitus, none of the patients reinitiated TEVIMBRA after symptom improvement.

Immune-Mediated Nephritis with Renal Dysfunction

TEVIMBRA can cause immune-mediated nephritis, which can be fatal.

Immune-mediated nephritis with renal dysfunction occurred in 0.3% (5/1972) of patients receiving TEVIMBRA, including Grade 3 (0.1%) and Grade 2 (0.2%) adverse reactions. TEVIMBRA was permanently discontinued in 1 (0.1%) patient and treatment was withheld in 3 (0.2%) patients. Three (60%) of the 5 patients received systemic corticosteroids. All 3 (60%) of the 5 patients received high-dose systemic corticosteroids. Nephritis with renal dysfunction resolved in 40.0% of the 5 patients. Of the 3 patients in whom TEVIMBRA was withheld for nephritis, 2 (66.7%) reinitiated TEVIMBRA after symptom improvement and one (50%) patient had recurrence of nephritis.

Immune-Mediated Dermatologic Adverse Reactions

TEVIMBRA can cause immune-mediated rash or dermatitis. Cases of severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported, some with fatal outcome. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue TEVIMBRA depending on severity.

Immune-mediated dermatologic adverse reactions occurred in 15.3% (301/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%), Grade 3 (0.9%) and Grade 2 (3.5%) adverse reactions. Dermatologic adverse reactions led to permanent discontinuation of TEVIMBRA in 2 (0.1%) patients and withholding of TEVIMBRA in 18 (0.9%) patients. Thirty (10.0%) of the 301 patients received systemic corticosteroids. Thirteen (4.3%) of the 301 patients received high-dose systemic corticosteroids. Immune-mediated skin reactions resolved in 190 (63.1%) of the 301 patients. Of the 18 patients in whom TEVIMBRA was withheld for dermatologic adverse reactions, 15 (83.3%) reinitiated TEVIMBRA after symptom improvement; of these, 1 (6.7%) patient had recurrence of immune-mediated dermatologic adverse reactions.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of less than 1% each in 1972 patients who received TEVIMBRA: myositis, myocarditis, arthritis, polymyalgia rheumatica, and pericarditis.

The following additional clinically significant immune-mediated adverse reactions have been reported with other PD-1/PD-L1 blocking antibodies, including severe or fatal cases.

Cardiac/Vascular: Vasculitis.

Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy.

Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.­­

Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.

Musculoskeletal and Connective Tissue: Polymyositis, rhabdomyolysis and associated sequelae including renal failure.

Endocrine: Hypoparathyroidism.

Other (Hematologic/Immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection.

Infusion-Related Reactions

TEVIMBRA can cause severe or life-threatening infusion-related reactions. Infusion-related reactions occurred in 5% (99/1972) patients receiving TEVIMBRA, including Grade 3 or higher (0.2%) reactions. Monitor patients for signs and symptoms of infusion-related reactions.

Slow the rate of infusion for mild (Grade 1) and interrupt the infusion for moderate (Grade 2) infusion-related reactions. For severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions, stop infusion and permanently discontinue TEVIMBRA.

Complications of Allogeneic HSCT

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action, TEVIMBRA can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TEVIMBRA and for 4 months after the last dose.

ADVERSE REACTIONS

First-line Treatment of Unresectable Advanced or Metastatic Esophageal Carcinoma (ESCC)

Permanent discontinuation of TEVIMBRA due to adverse reactions occurred in 13% of patients. The adverse reaction which resulted in discontinuation in ≥2% of patients was pneumonitis (2.2%).

Dosage interruptions of TEVIMBRA due to adverse reactions occurred in 52% of patients. Adverse reactions which required dosage interruption in ≥2% of patients were neutrophil count decreased (7%), fatigue (6%), pneumonia (6%), anemia (4.3%), neutropenia (4.3%), white blood cell count decreased (4.3%), rash (3.7%), dysphagia (2.8%), platelet count decreased (2.8%), pyrexia (2.8%), and diarrhea (2.2%).

The most common (≥20%) adverse reactions, including laboratory abnormalities were decreased neutrophil count, decreased sodium, increased glucose, anemia, fatigue, decreased appetite, increased AST, decreased potassium, increased serum creatinine, decreased calcium, increased ALT, diarrhea, stomatitis, and vomiting.

Previously Treated Unresectable Advanced or Metastatic ESCC

Permanent discontinuation of TEVIMBRA due to an adverse reaction occurred in 19% of patients. Adverse reactions which resulted in permanent discontinuation in ≥1% of patients were hemorrhage, pneumonitis (including pneumonitis and immune-mediated pneumonitis), and pneumonia.

Dosage interruptions of TEVIMBRA due to an adverse reaction occurred in 23% of patients. Adverse reactions which required dosage interruptions in ≥2% of patients were pneumonia, pneumonitis, and fatigue.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase, anemia, fatigue, increased AST, musculoskeletal pain, decreased weight, increased ALT, and cough.

Treatment of Previously Untreated Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (G/GEJ)

Permanent discontinuation of TEVIMBRA due to an adverse drug reaction occurred in 16% of patients. Adverse drug reactions which resulted in permanent discontinuation in ≥1% of patients were death, fatigue, and pneumonitis.

Dosage interruption of TEVIMBRA in the TEVIMBRA plus chemotherapy arm due to an adverse drug reaction occurred in 49% of patients. Adverse drug reactions which required dosage modifications in ≥2% of patients were, platelet count decreased (12%), neutrophil count decreased (10%), neutropenia (6%), white blood cell count decreased (6%), increased AST (4.8%), increased ALT (3.8%), increased blood bilirubin (3%), COVID-19 (3%), thrombocytopenia (2.8%), leukopenia (2.6%), pneumonitis (2.2%), and pneumonia (2%).

The most common (≥20%) adverse reactions, including laboratory abnormalities, for TEVIMBRA in combination with chemotherapy were nausea, fatigue, decreased appetite, anemia, peripheral sensory neuropathy, vomiting, decreased platelet count, decreased neutrophil count, increased aspartate aminotransferase, diarrhea, abdominal pain, increased alanine aminotransferase, decreased white blood cell count, decreased weight, and pyrexia.

INDICATIONS

TEVIMBRA is a programmed death receptor-1 (PD-1)-blocking antibody indicated for:

Esophageal Cancer

in combination with platinum-containing chemotherapy for the first-line treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥1).
as a single-agent, for the treatment of adults with unresectable or metastatic ESCC after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor.
Gastric Cancer

in combination with platinum and fluoropyrimidine-based chemotherapy for the first-line treatment of adults with unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (≥1).
Please see full U.S. Prescribing Information including the U.S. Medication Guide.