On April 30, 2021 Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) reported financial results for the first quarter of 2021 (Press release, Alexion, APR 30, 2021, View Source [SID1234578891]). Total revenues in the first quarter were $1,636.5 million, a 13 percent increase compared to the same period in 2020. The positive impact of foreign currency on total revenues year-over-year was less than 1 percent inclusive of hedging activities. On a GAAP basis, diluted EPS attributable to Alexion in the first quarter of 2021 was $2.86, a 14 percent increase versus the first quarter of 2020. Non-GAAP diluted EPS attributable to Alexion for the first quarter of 2021 was $3.52, a 9 percent increase versus the first quarter of 2020.

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"We are off to a strong start in 2021, with continued advancement of our LEAD-EXPAND-DIVERSIFY strategy to progress our commercial portfolio as well as our many development programs," said Ludwig Hantson, Ph.D., Chief Executive Officer of Alexion. "I am so proud of our teams’ ongoing dedication and execution, which are further advancing our mission of delivering life-changing medicines to people with rare diseases and devastating conditions. We are well positioned to build on our success and momentum as the year progresses and once we become part of AstraZeneca."

First Quarter 2021 Financial Highlights

Net product sales were $1,635.7 million in the first quarter of 2021, compared to $1,444.6 million in the first quarter of 2020.
SOLIRIS net product sales were $1,027.6 million, compared to $1,022.9 million in the first quarter of 2020, representing a 0.5 percent increase.
ULTOMIRIS net product sales were $346.9 million, compared to $222.8 million in the first quarter of 2020, representing a 56 percent increase.
STRENSIQ net product sales were $197.5 million, compared to $172.2 million in the first quarter of 2020, representing a 15 percent increase.
KANUMA net product sales were $34.8 million, compared to $26.7 million in the first quarter of 2020, representing a 30 percent increase.
ANDEXXA/ONDEXXYA net product sales were $28.9 million in the first quarter of 2021.
GAAP cost of sales was $125.4 million, compared to $111.7 million in the first quarter of 2020. Non-GAAP cost of sales was $113.8 million, compared to $108.6 million in the first quarter of 2020.
GAAP R&D expense was $289.1 million, compared to $200.9 million in the first quarter of 2020. Non-GAAP R&D expense was $267.0 million, compared to $185.7 million in the first quarter of 2020.
GAAP SG&A expense was $342.9 million, compared to $319.9 million in the first quarter of 2020. Non-GAAP SG&A expense was $292.2 million, compared to $259.1 million in the first quarter of 2020.
GAAP income tax expense was $113.4 million, compared to income tax expense of $106.0 million in the first quarter of 2020. Non-GAAP income tax expense was $145.7 million, compared to income tax expense of $141.2 million in the first quarter of 2020.
GAAP diluted EPS attributable to Alexion was $2.86, compared to $2.50 in the first quarter of 2020. Non-GAAP diluted EPS attributable to Alexion was $3.52, compared to $3.22 in the first quarter of 2020.
Research and Development

PHASE 3/4

SOLIRIS – Guillain-Barre Syndrome (GBS): SOLIRIS in GBS has been granted SAKIGAKE designation by Japan’s Ministry of Health, Labour and Welfare (MHLW). In February 2021, Alexion initiated a Phase 3 study of SOLIRIS in GBS in Japan and dosing is underway.
ULTOMIRIS – 100 mg/mL: An application for approval of the ULTOMIRIS 100 mg/mL formulation for PNH and aHUS is under review in Japan. This higher concentration formulation is designed to reduce infusion time by more than 60 percent to approximately 45 minutes.
ULTOMIRIS – Subcutaneous: The Phase 3 study of weekly subcutaneous (SC) ULTOMIRIS demonstrated PK-based non-inferiority versus intravenous ULTOMIRIS. Pending collection of 12-month safety and drug-device combination data, Alexion plans to file for approval in the U.S. for the ULTOMIRIS SC formulation and device combination in PNH and aHUS in the third quarter of 2021, and in the EU in the first quarter of 2022.
ULTOMIRIS – Paroxysmal Nocturnal Hemoglobinuria (PNH): The U.S. FDA granted priority review for ULTOMIRIS in children and adolescents with PNH and has set a Prescription Drug User Fee Act (PDUFA) target action date of June 7, 2021.
ULTOMIRIS – gMG: Enrollment is complete in the Phase 3 study of ULTOMIRIS in adults with gMG. Study results are expected in the second half of 2021.
ULTOMIRIS – NMOSD: In March 2021, Alexion completed enrollment in the Phase 3 study of ULTOMIRIS in NMOSD.
ULTOMIRIS – Amyotrophic Lateral Sclerosis (ALS): In March 2021, Alexion completed enrollment in the Phase 3 study of ULTOMIRIS in ALS. Study results are expected in the first half of 2022.
ULTOMIRIS – Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (HSCT-TMA): Phase 3 studies of ULTOMIRIS in adults and children with HSCT-TMA are underway.
ULTOMIRIS – Complement Mediated Thrombotic Microangiopathy (CM-TMA): Alexion plans to initiate a Phase 3 study of ULTOMIRIS in CM-TMA in the second quarter of 2021.
ULTOMIRIS – Severe COVID-19: Further enrollment in a Phase 3 trial of ULTOMIRIS in adults hospitalized with severe COVID-19 requiring mechanical ventilation is paused, due to lack of efficacy, pending further analysis of the data. Alexion continues to provide ULTOMIRIS for the ongoing TACTIC-R platform study led by Cambridge University Hospitals NHS Foundation Trust, which is evaluating the potential of earlier immune modulatory treatment (hospitalized patients not requiring mechanical ventilation) in preventing progression of the virus.
ULTOMIRIS – Dermatomyositis (DM): Alexion plans to initiate a Phase 2/3 study of ULTOMIRIS in DM in the second half of 2021, pending regulatory feedback.
ALXN1840 – Wilson Disease: Enrollment and dosing are complete in a Phase 3 study of ALXN1840 in Wilson disease. Study results are expected in the third quarter of 2021.
CAEL-101 – Caelum Biosciences: Alexion and Caelum Biosciences are conducting the Cardiac Amyloid Reaching for Extended Survival (CARES) Phase 3 clinical program to evaluate CAEL-101, a first-in-class amyloid fibril targeted therapy, in combination with standard-of-care therapy in AL amyloidosis. Two parallel Phase 3 studies – one in patients with Mayo stage IIIa disease and one in patients with Mayo stage IIIb disease – are underway.
ALXN2060 (AG10): Alexion holds an exclusive license to develop and commercialize ALXN2060 (AG10) in Japan. Eidos is currently evaluating AG10 in two Phase 3 studies in the U.S. and Europe – one for ATTR cardiomyopathy (ATTR-CM) and one for ATTR polyneuropathy (ATTR-PN). Alexion is conducting a Phase 3 bridging study of ALXN2060 for patients with ATTR-CM in Japan.
ALXN2040 (Danicopan) – PNH with Extravascular Hemolysis (EVH): A Phase 3 study of ALXN2040 as an add-on therapy for PNH patients with EVH is underway.
ANDEXXA/ONDEXXYA – Acute Intracranial Hemorrhage (ICH): The Phase 4 ANNEXA-I study – designed to provide clinical data supporting full approval – is underway to assess ANDEXXA compared to usual standard of care in patients presenting with acute intracranial hemorrhage while taking an oral Factor Xa inhibitor. In addition, a supplemental Biologics License Application (sBLA) is under review by the U.S. FDA to enable the addition of edoxaban and enoxaparin to the U.S. label. In February 2021, Alexion filed for regulatory approval of ONDEXXYA in Japan.
PHASE 1/2

ULTOMIRIS – Renal Diseases: A proof-of-concept study of ULTOMIRIS in patients with IgA nephropathy and lupus nephritis is underway.
ALXN1830: Due to COVID-19, Alexion discontinued the Phase 2 study of ALXN1830, administered intravenously, in warm autoimmune hemolytic anemia (WAIHA) and the Phase 1 study of a subcutaneous formulation of ALXN1830 in healthy volunteers. In March 2021, Alexion initiated a new Phase 1 study of subcutaneous ALXN1830 in healthy volunteers. Following successful completion of this Phase 1 study, Alexion plans to initiate Phase 2 studies of subcutaneous ALXN1830 in gMG and WAIHA in 2021, pending regulatory feedback.
ALXN2040 – Geographic Atrophy (GA): In March 2021, Alexion submitted an Investigational New Drug (IND) application for ALXN2040 in GA and plans to initiate a Phase 2 study in the second half of 2021.
ALXN2040 – COVID-19: Alexion has agreed to provide ALXN2040 to the U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, for the ACTIV-5 Big Effect Trial in adults hospitalized with COVID-19. This Phase 2 platform trial is comparing different investigational therapies to a common control arm with the intent of identifying promising treatments to enter a more definitive study.
ALXN2050 – PNH: Alexion has re-initiated additional enrollment in the Phase 2 study of ALXN2050 monotherapy in PNH patients, following the receipt of Phase 1 data that support further dose escalation in the Phase 2 study.
ALXN2050 – Renal Diseases: Alexion plans to initiate a proof-of-concept study of ALXN2050 in patients with various renal diseases in 2021, pending regulatory feedback.
ALXN1720: The Phase 1 healthy volunteer study of ALXN1720, a novel anti-C5 albumin-binding bi-specific mini-body that is designed to bind and prevent activation of human C5, has been paused for a second time due to COVID-19, but is expected to resume in the second quarter of 2021. Additional cohorts have been added to the study to explore higher doses and enable the initiation of a Phase 3 study in gMG, pending successful completion of the Phase 1 study as has been agreed with the U.S. FDA. Data from the Phase 1 study are expected in the second half of 2021. Alexion also plans to initiate a study of ALXN1720 in DM.
ANDEXXA – Urgent Surgery: ANDEXXA is currently being evaluated in a single-arm, open-label Phase 2 study in patients taking apixaban, rivaroxaban, edoxaban, or enoxaparin who require urgent surgery. The results of this study will inform the design of a randomized controlled Phase 3 clinical trial to expand the label in this population.
ALXN2075 (cerdulatinib): Acquired as part of the Portola acquisition, ALXN2075 is a dual spleen tyrosine kinase and janus kinase (SYK/JAK) inhibitor being evaluated in a Phase 1/2a study in patients with relapsed/refractory chronic lymphocytic leukemia or B-cell or T-cell non-Hodgkin lymphoma. Data are expected in the second quarter of 2021.
ALXN1820: A Phase 1 study of ALXN1820, Alexion’s bi-specific anti-properdin mini-body, is underway in healthy volunteers.
ALXN1850 – Hypophosphatasia (HPP): Alexion plans to initiate a Phase 1 study of ALXN1850 in adults with HPP in the second quarter of 2021, pending regulatory feedback.
COVID-19

We continue to take steps to proactively respond to the evolving COVID-19 pandemic and to plan for related uncertainties. We remain focused on continuing to serve patients, protecting the health and safety of our employees and the communities in which we live and work, and supporting patients in clinical trials. We are also focused on minimizing potential interactions that could contribute to the spread of the virus and put additional strain on healthcare systems through the use of innovative virtual means where possible.

Clinical Trials: We have implemented a pandemic response business continuity plan designed to protect patients and site staff safety while continuing our clinical trials with limited interruption to the extent we are able. The COVID-19 impact has varied by study and program, but there has been little timing impact on fully-enrolled trials and the majority of studies that had been temporarily paused due to the pandemic have resumed. A small number of clinical trial sites are restricting site visits and imposing restrictions on the initiation of new trials and patient visits to protect both site staff and patients from possible COVID-19 exposure. Based on local dynamics where these studies are being conducted, there has been, and may continue to be, an impact to the timing of trials that are enrolling patients and activating sites, or have not yet started to do so. We are actively implementing remote and local procedures under the guidance of regulatory authorities.
Business Impact: We continue to take proactive measures designed to mitigate the risk of potential interruptions in supply and/or access to patients’ customary site-of-care locations. Treatment compliance rates across all our medicines have remained strong. We have also seen the predicted slowing of new patient initiations and delays in treatment starts, and we are continuing to closely monitor this environment as the pandemic continues.
Conference Call/Earnings Materials:

Given the agreement for Alexion to be acquired by AstraZeneca, Alexion will not be hosting a conference call. Earnings materials are available publicly on the Investor Relations page of our website at View Source Questions may be directed to the Investor Relations team via e-mail at [email protected] or the contact information below.

On April 29, 2021 Lantern Pharma (NASDAQ: LTRN), a clinical stage biopharmaceutical company using its proprietary RADR artificial intelligence ("A.I.") platform to improve drug discovery and development and identify patients who will benefit from its portfolio of targeted oncology therapeutics, reported that RADR has exceeded 4.6 billion datapoints (Press release, Lantern Pharma, APR 29, 2021, View Source;utm_medium=rss&utm_campaign=radr-surpasses-4-6-billion-datapoints-accelerating-progress [SID1234578775]). This 16-fold increase in datapoints over the past 12 months was also accompanied by other significant improvements in the functionality, feature-set and automation of the drug development platform as well as a significant increase in the number of drugs, drug classes and cancers covered by RADR.

"We are extremely pleased to share the fact that we have increased the number of biologically relevant and curated datapoints that power our RADR platform by 16-fold since last May and nearly 4-fold since the beginning of the year. The pace of data acquisition, curation, and tagging achieved during this last campaign is well ahead of schedule and allows us to increasingly focus on building a more complete and more powerful library of algorithms and machine learning models aimed at rapidly answering questions that are fundamental to oncology drug development," stated Panna Sharma, President and CEO of Lantern Pharma. "Our mission to build the world’s largest, most robust and most accurate A.I. driven platform for precision oncology drug discovery and development is advancing rapidly. The robustness of the datasets powering RADR is anticipated to continue to improve machine-learning results, accelerate automation of other features and aid oncology drug development for Lantern and our partners with the ultimate focus of benefitting cancer patients."

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Lantern is committed to growing and enhancing RADR, which it believes is among the largest drug development platforms powered exclusively for oncology drug development and rescue. The growing datapoints, and accompanying functionality in the A.I. platform, allow scientists, biologists, and engineers to collaborate on issues of drug activity, drug response, patient stratification, and cancer biomarkers at a pace which has been unachievable, until now. The developmental focus on increasing the number of datapoints, and improving the performance, power and biological relevance of the algorithms, is expected to yield additional targeted indications for Lantern’s current pipeline of drug candidates. We expect that the platform will also help in revealing additional compounds and therapies that can be in-licensed and subsequently developed in a more efficient, and potentially more targeted manner. Lantern has used RADR to uncover indications in multiple cancer sub-types, including CNS (central nervous system) cancers, drug-resistant lung cancers, lung cancer sub-types among never-smokers and SMARCB1 mutated cancers (e.g. Atypical Teratoid Rhabdoid Tumors).

Lantern has filed two additional patent applications directed to the RADR platform that further strengthen the Company’s leading position in using A.I. for cancer drug development and drug rescue. The Company’s patent applications are directed to using machine learning to predict and discover gene signatures associated with pharmaceutical agents, as well as using automated and machine learning methods on genomic and biomarker data for rescuing, repurposing and repositioning of pharmaceutical agents. Lantern expects to continue developing novel A.I. and machine learning functionality, methods and technologies that it will file patents on both as core technologies and directed in the use of its pipeline of drug candidates.

"As A.I. continues to transform drug development, platforms that can provide a machine-learning, A.I. driven edge are becoming an essential tool for companies to make informed, rapid decisions in cancer indication selection, trial design, validation of mechanisms and potential creation of combination therapy regimens," continued Sharma. "Now, with every major cancer and drug class being covered in our A.I. platform, Lantern can focus not only on accelerating our portfolio, but also on developing collaborations that continue to enhance and validate our platform while delivering insights for our biopharma partners. These RADR powered insights are expected to accelerate development timelines, derisk key decisions and uncover new opportunities that may have gone undeveloped — ultimately leading to oncology therapies that can increase the personalization of treatment."

"Biopharma companies are looking to launch programs in validated indications more rapidly as they focus on maximizing the potential of each drug candidate," said Mr. Sharma. "We believe that RADR can help design and launch these programs, that continue to grow in complexity, at a fraction of the cost and timeline of traditional oncology drug development. Creating novel genomic and mechanistic insights while also providing specific guidance on designing biomarker driven preclinical studies and clinical trials is an essential component of personalizing cancer treatment. RADR is a powerful platform that can offer a significant competitive advantage for oncology drug development."

On April 29, 2021 Bristol Myers Squibb (NYSE:BMY) reported results for the first quarter of 2021, which reflect continued sales growth and advancement of the company’s product pipeline across our four core therapeutic areas (Press release, Bristol-Myers Squibb, APR 29, 2021, View Source [SID1234578792]).

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"We continue to deliver solid growth, execute against our strategic priorities and make meaningful progress across our pipeline," said Giovanni Caforio, M.D., board chair and chief executive officer, Bristol Myers Squibb. "I am proud of our team’s hard work and dedication, which led to important milestones with significant potential to benefit patients across multiple disease states. These accomplishments, combined with our financial strength and flexibility, further advance our opportunity to renew our portfolio and drive long-term sustainable growth."

FIRST QUARTER FINANCIAL RESULTS

All comparisons are made versus the same period in 2020 unless otherwise stated.

Bristol Myers Squibb posted first quarter revenues of $11.1 billion, an increase of 3%, or 1% when adjusted for foreign exchange. Excluding COVID-19 related buying patterns from the prior year period, first quarter revenues grew 8%.
U.S. revenues increased 4% to $7.0 billion in the quarter. International revenues increased 1% to $4.1 billion in the quarter. When adjusted for foreign exchange impact, international revenues decreased 5%.
Gross margin increased from 66.0% to 74.3% in the quarter primarily due to lower unwinding of inventory purchase price accounting adjustments, partially offset by an impairment charge related to the Inrebic marketed product rights and foreign exchange. On a non-GAAP basis, gross margin decreased from 79.4% to 78.1% in the quarter driven by foreign exchange.
Marketing, selling and administrative expenses increased 4% to $1.7 billion in the quarter primarily due to higher advertising and promotion expenses. On a non-GAAP basis, marketing, selling and administrative expenses increased 5% to $1.7 billion in the quarter primarily due to higher advertising and promotion expenses.
Research and development expenses decreased 6% to $2.2 billion in the quarter primarily due to lower site exit costs and license and asset acquisition charges and other specified items related to the Celgene acquisition in the same period a year ago. On a non-GAAP basis, research and development expenses decreased 1% to $2.2 billion.
Amortization of acquired intangible assets increased $231 million to $2.5 billion in the quarter.
The effective tax rate was 19.8% in the quarter. Income taxes were $462 million despite a pre-tax loss of $304 million in the same period a year ago primarily due to certain non-deductible expenses and purchase price adjustments. On a non-GAAP basis, the effective tax rate was 16.8% in the quarter and 16.0% in the same period a year ago.
The company reported net earnings attributable to Bristol Myers Squibb of $2.0 billion, or $0.89 per share, in the first quarter, compared to net loss of $775 million, or $0.34 per share, for the same period a year ago.
The company reported non-GAAP net earnings attributable to Bristol Myers Squibb of $4.0 billion, or $1.74 per share, in the first quarter, compared to non-GAAP net earnings of $4.0 billion, or $1.72 per share, for the same period a year ago.
A discussion of the non-GAAP financial measures is included under the "Use of Non-GAAP Financial Information" section.

FIRST QUARTER PRODUCT AND PIPELINE UPDATE

Cardiovascular

mavacamten

Regulatory

In March, the company announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for mavacamten, an investigational, novel, oral, allosteric modulator of cardiac myosin, for patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). The FDA has assigned a Prescription Drug User Fee Act (PDUFA) goal date of January 28, 2022. (link)
Oncology

Opdivo

Regulatory

In April, the company announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of Opdivo (nivolumab) plus Yervoy(ipilimumab) for the first-line treatment of adults with unresectable malignant pleural mesothelioma (MPM). The positive CHMP opinion is based on results from CheckMate -743, which demonstrated superior overall survival with Opdivo plus Yervoy vs. chemotherapy. (link)
In April, the company announced the FDA approved Opdivo in combination with fluoropyrimidine- and platinum-containing chemotherapy for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, regardless of PD-L1 expression status. The approval is based on results from the CheckMate -649 trial. (link)
In April, the company announced that the European Commission (EC) has approved Opdivo in combination with Cabometyx (cabozantinib) for the first-line treatment of adults with advanced renal cell carcinoma. The EC’s decision is based on results from the Phase 3 CheckMate -9ER trial, which demonstrated superior efficacy with Opdivo in combination with Cabometyx vs. sunitinib. (link)
In March, the company announced that the EMA has validated its type II variation application for Opdivo for the adjuvant treatment of patients with surgically resected, high-risk muscle-invasive urothelial carcinoma. The application is based on results from the CheckMate -274 trial, which showed that Opdivo increased disease-free survival and was well tolerated by patients. Validation of the application confirms the submission is complete and begins the EMA’s centralized review process. (link)
In February, the company announced that the CHMP of the EMA has recommended approval of Opdivo in combination with Cabometyx for the first-line treatment of adults with advanced RCC. The recommendation is based on the Phase 3 CheckMate -9ER trial and the European Commission (EC), which has the authority to approve medicines for the European Union (EU), will now review the CHMP recommendation. (link)
Clinical

In April, the company announced results from the CheckMate -648 study, evaluating treatment with Opdivo plus chemotherapy or Opdivo plus Yervoy in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC). The study showed statistically significant and clinically meaningful improvements in: overall survival in patients whose tumors expressed PD-L1 with both Opdivo plus Yervoy and Opdivo plus chemotherapy; overall survival in the all-randomized patient population with both Opdivo plus Yervoy and Opdivo plus chemotherapy; and progression-free survival in patients whose tumors express PD-L1 with Opdivo plus chemotherapy. The study did not meet the endpoint of progression-free survival in patients whose tumors express PD-L1 with use of Opdivo plus Yervoy. (link)
relatlimab

Clinical

In March, the company announced primary results from the Phase 2/3 RELATIVITY-047 (CA224-047) trial evaluating the fixed-dose combination of relatlimab, an anti-LAG-3 antibody, and Opdivo versus Opdivo alone in patients with previously untreated metastatic or unresectable melanoma. The trial met its primary endpoint of progression-free survival (PFS). (link)
Medical Conferences

In April, during a plenary session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021:
The company announced results from the CheckMate -816 study, which showed that neoadjuvant treatment with three cycles of Opdivo plus chemotherapy significantly improved pathologic complete response (pCR), a primary endpoint, compared to chemotherapy alone in patients with resectable stage Ib to IIIa non-small cell lung cancer (NSCLC). (link)
In February during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Genitourinary Cancers Symposium:
The company announced results from the Phase 3 CheckMate -274 trial, which showed that Opdivo significantly improved disease-free survival (DFS) as an adjuvant treatment across all randomized patients with surgically resected, high-risk muscle-invasive urothelial carcinoma and in the subgroup of patients whose tumors express PD-L1 ≥1%, meeting both of the study’s primary endpoints. CheckMate -274 is the first positive Phase 3 trial evaluating an immunotherapy in the adjuvant setting of muscle-invasive urothelial carcinoma. (link)
The company and Exelixis, Inc.(NASDAQ: EXEL) announced results from new analyses from the Phase 3 CheckMate -9ER trial, demonstrating clinically meaningful, sustained efficacy benefits as well as quality of life improvements with the combination of Opdivo and Cabometyx compared to sunitinib in the first-line treatment of advanced RCC. (link)
Hematology

Onureg

Regulatory

In April, the company announced that CHMP of the EMA has recommended approval of Onureg (azacitidine tablets; CC-486) as a maintenance therapy in adult patients with acute myeloid leukemia (AML) who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following induction therapy with or without consolidation treatment and who are not candidates for, including those who choose not to proceed to, hematopoietic stem cell transplantation (HSCT). (link)
Abecma

Regulatory

In March, the company and bluebird bio, Inc. (NASDAQ: BLUE) announced that the FDA has approved Abecma(idecabtagene vicleucel; ide-cel) as the first B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. (link)
Breyanzi

Regulatory

In February, the company announced that the FDA has approved Breyanzi (lisocabtagene maraleucel: liso-cel), a CD19-directed CAR T cell therapy for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma(LBCL) after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. (link)
Inrebic

Regulatory

In February, the company announced that the European Commission (EC) has granted full Marketing Authorization for Inrebic (fedratinib) for the treatment of disease-related splenomegaly (enlarged spleen) or symptoms in adult patients with primary myelofibrosis, post-polycythaemia vera myelofibrosis or post-essential thrombocythaemia myelofibrosis, who are Janus Associated Kinase (JAK) inhibitor naïve or have been treated with ruxolitinib. (link)
Immunology

deucravacitinib

Medical Conferences

In April, at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX), the company announced positive results from the POETYK PSO-1 and POETYK PSO-2 Phase 3 trials evaluating deucravacitinib, a potential first-in-class, oral, selective tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action, for the treatment of patients with moderate to severe plaque psoriasis.(link)
Capital Allocation

The company continues to maintain a consistent, balanced approach to capital allocation, focused on prioritizing investment for growth through business development along with reducing debt, commitment to dividend and share repurchases.

In March, the company purchased approximately $4.0 billion in aggregate purchase price of certain debt securities in a series of cash tender offers and "make whole" redemptions.
Commitment to Environmental Sustainability, Diversity and Inclusion, Health Equity

In February, the company announced the donation of a total of $11 million to 56 nonprofit organizations focused on advancing health equity in the United States. These organizations will deliver programs to improve access to high-quality care as well as increase disease awareness and education in racially and ethnically diverse and medically underserved communities, and to improve diversity in clinical research. (link)
COVID-19 Pandemic Response

During the current world health crisis, the company continues to take all necessary actions to promote public health by carrying out its mission of providing life-saving medicines to the patients who depend on the company, conducting research and supporting relief efforts across the globe. (link)

Financial Guidance

Bristol Myers Squibb is updating its 2021 GAAP EPS guidance range of $3.12-$3.32 to $3.18-$3.38 and affirming its non-GAAP EPS guidance range of $7.35 – $7.55. Both GAAP and non-GAAP guidance assume current exchange rates. Key 2021 GAAP and non-GAAP line item guidance assumptions are:

Worldwide revenues increasing in the high-single digits.
Gross margin as a percentage of revenue is expected to be approximately 79% for GAAP and approximately 80.5% for non-GAAP.
Marketing, selling and administrative expenses to be in-line with 2020 levels for GAAP and increasing in the low-single digit range for non-GAAP.
Research and development expenses decreasing in the low-double digits for GAAP and increasing in the mid-single digits for non-GAAP.
An effective tax rate of approximately 22% for GAAP and approximately 16% for non-GAAP.
The 2021 financial guidance excludes the impact of any potential future strategic acquisitions and divestitures, and any specified items that have not yet been identified and quantified. The 2021 non-GAAP EPS guidance is explained and further excludes other specified items as discussed under "Use of Non-GAAP Financial Information." The financial guidance is subject to risks and uncertainties applicable to all forward-looking statements as described elsewhere in this press release.

Company and Conference Call Information

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook, and Instagram.

There will be a conference call on April 29, 2021 at 9 a.m. ET during which company executives will review financial information and address inquiries from investors and analysts. Investors and the general public are invited to listen to a live webcast of the call at View Source or by dialing in the U.S. toll free 800-458-4121 or international +1 313-209-6672, confirmation code: 3705525, or using this link which becomes active 15 minutes prior to the scheduled start time and entering your information to be connected. Materials related to the call will be available at the same website prior to the conference call.

A replay of the call will be available beginning at 12:30 p.m. ET on April 29 through 12:30 p.m. ET on May 13, 2021. The replay will also be available through View Source or by dialing in the U.S. toll free 888-203-1112 or international 719-457-0820, confirmation code: 3705525.

Use of Non-GAAP Financial Information

In discussing financial results and guidance, the company refers to the financial measures that are not in accordance with U.S. Generally Accepted Accounting Principles (GAAP). The non-GAAP financial measures are provided as supplemental information to the financial measures presented in this press release that are calculated and presented in accordance with GAAP and are presented because management has evaluated the company’s financial results both including and excluding the adjusted items or the effects of foreign currency translation, as applicable, and believes that the non-GAAP financial measures presented portray the results of the company’s baseline performance, supplement or enhance management, analysts and investors overall understanding of the company’s underlying financial performance and trends and facilitate comparisons among current, past and future periods. For example, non-GAAP earnings and EPS information are indications of the company’s baseline performance before items that are considered by us to not be reflective of the company’s ongoing results. This information is among the primary indicators that we use as a basis for evaluating performance, allocating resources, setting incentive compensation targets and planning and forecasting for future periods. In addition, revenue excluding COVID-19 related buying patterns from the first quarter of 2020, non-GAAP gross margin, which is gross profit excluding certain specified items as a percentage of revenues, non-GAAP marketing, selling and administrative expenses, which is marketing, selling and administrative expense excluding certain specified items, and non-GAAP research and development expenses, which is research and development expenses excluding certain specified items, are relevant and useful for investors because they allow investors to view performance in a manner similar to the method used by our management and make it easier for investors, analysts and peers to compare our operating performance to other companies in our industry and to compare our year-over-year results. This earnings release also provides international revenues excluding the impact of foreign exchange. Foreign exchange impacts were derived by applying the prior period average currency rates to the current period revenues and expenses.

Non-GAAP financial measures such as non-GAAP earnings and related EPS information are adjusted to exclude certain costs, expenses, gains and losses and other specified items that are evaluated on an individual basis after considering their quantitative and qualitative aspects and typically have one or more of the following characteristics, such as being highly variable, difficult to project, unusual in nature, significant to the results of a particular period or not indicative of past or future operating results. These items are excluded from non-GAAP earnings and related EPS information because the company believes they neither relate to the ordinary course of the company’s business nor reflect the company’s underlying business performance. Similar charges or gains were recognized in prior periods and will likely reoccur in future periods, including amortization of acquired intangible assets, including product rights that generate a significant portion of our ongoing revenue and will recur until the intangible assets are fully amortized, unwind of inventory fair value adjustments, acquisition and integration expenses, restructuring costs, accelerated depreciation and impairment of property, plant and equipment and intangible assets, R&D charges or other income resulting from upfront or contingent milestone payments in connection with the acquisition or licensing of third-party intellectual property rights, divestiture gains or losses, stock compensation resulting from accelerated vesting of Celgene awards, certain retention-related employee compensation charges related to the Celgene transaction, pension, legal and other contractual settlement charges, equity investment and contingent value rights fair value adjustments (including fair value adjustments attributed to limited partnership equity method investments beginning in 2021) and amortization of fair value adjustments of debt acquired from Celgene in our 2019 exchange offer, among other items. Deferred and current income taxes attributed to these items are also adjusted for considering their individual impact to the overall tax expense, deductibility and jurisdictional tax rates.

Because the non-GAAP financial measures are not calculated in accordance with GAAP, they should not be considered superior to and are not intended to be considered in isolation or as a substitute for the related financial measures presented in the press release that are prepared in accordance with GAAP and may not be the same as or comparable to similarly titled measures presented by other companies due to possible differences in method and in the items being adjusted. We encourage investors to review our financial statements and publicly-filed reports in their entirety and not to rely on any single financial measure.

Reconciliations of the non-GAAP financial measures to the most comparable GAAP measures are provided in the accompanying financial tables and also available on the company’s website at www.bms.com.

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We routinely post important information for investors on our website, BMS.com, in the "Investors" section. We may use this website as a means of disclosing material, non-public information and for complying with our disclosure obligations under Regulation FD. Accordingly, investors should monitor the Investors section of our website, in addition to following our press releases, SEC filings, public conference calls, presentations and webcasts. We may also use social media channels to communicate with our investors and the public about our company, our products and other matters, and those communications could be deemed to be material information. The information contained on, or that may be accessed through, our website or social media channels are not incorporated by reference into, and are not a part of, this document.

On April 29, 2021 Morphic Therapeutic (Nasdaq: MORF), a biopharmaceutical company developing a new generation of oral integrin therapies for the treatment of serious chronic diseases, reported its corporate highlights and financial results for the first quarter of 2021 (Press release, Morphic Therapeutic, APR 29, 2021, View Source [SID1234578811]).

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Recent Highlights and Outlook

•Expanded research and development collaboration with Janssen Pharmaceuticals for a third program, focused on activating antibodies against a new integrin target
•Announced positive preliminary results from Phase 1 single ascending dose portion of MORF-057 Phase 1 providing early clinical proof of concept for MORF-057 as an oral, selective α4β7 inhibitor
◦MORF-057 was well tolerated in all dose cohorts
◦MORF-057 achieved greater than 95% mean receptor occupancy of α4β7 integrin at three highest dose levels
◦Observed saturating levels of >99% RO in subjects in each cohort above 25mg
◦Morphic received an acceptance for its submission to present the complete MORF-057 Phase 1 data set at the ECCO’21 Virtual Congress in July 2021. This presentation will include additional data from the Phase 1 SAD study as well as results from the ongoing Phase 1 multiple ascending dose and food effect studies
•Completed $245 million upsized public offering of stock providing runway until the end of 2024
•Presented positive preclinical data from the αvβ8 immuno-oncology program demonstrating that Morphic’s small molecule inhibitors, in combination with checkpoint inhibitors, potentiated anti-tumor activity in tumors refractory to checkpoint inhibition monotherapy

"Morphic has made great strides in our mission to develop oral integrin medicines based on the MInT platform thus far in 2021. We made noteworthy advances across our proprietary and partnered integrin development programs as well as in the operational aspects of our business, including expanded partnerships, and the presentation of new data from emerging programs in our early integrin pipeline," commented Praveen Tipirneni, M.D., president and chief executive officer of Morphic Therapeutic. "Most importantly, we provided proof-of-concept data for MORF-057 in IBD, with a favorable tolerability profile and excellent pharmacodynamic data. Finally, based on our recent fund-raising, Morphic has a strong cash position as we approach additional MORF-057 data this year and then continue to advance our integrin-targeted therapeutic candidates created with the MInT platform."

Financial Results for the First Quarter 2021

•Net loss for the quarter ended March 31, 2021 was $21.3 million or $0.63 per share compared to a net loss of $16.7 million or $0.55 per share for the same quarter last year.
•Revenue was $3.3 million for the quarter ended March 31, 2021 compared to $5.6 million for the same quarter last year.
•Research and development expenses were $18.6 million for the quarter ended March 31, 2021 as compared to $19.0 million for the same quarter last year. The slight decrease was due to AbbVie’s option exercise for αvβ6 program in 2020 resulting in lower costs in 2021 offset with higher costs associated with Morphic’s wholly owned α4β7 program.
•General and administrative expenses were $6.0 million for the quarter ended March 31, 2021, compared to $4.4 million for the same quarter last year. The increase was primarily attributable to increased headcount and higher professional and consulting costs associated with Morphic operating as a public company.
As of March 31, 2021, Morphic had cash, cash equivalents and marketable securities of $448.3 million, compared to $228.3 million as of December 31, 2020. The increase was primarily due to the closing of the public offering of common stock in March. Morphic believes its cash, cash equivalents and marketable securities as of March 31, 2021, will be sufficient to fund operating expenses and capital expenditure requirements until the end of 2024.

On April 29, 2021 Eisai reported that the European Journal of Cancer published the results from a post hoc analysis of the Phase 3 SELECT study evaluating the impact of lung metastases on overall survival (OS) in patients with locally recurrent or metastatic, progressive radioiodine-refractory differentiated thyroid cancer (RAI-refractory DTC) who were treated with LENVIMA, an orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai (Press release, Eisai, APR 29, 2021, View Source [SID1234578848]). These data were originally presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting in September 2019.

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The analysis consisted of patients with any lung metastases, including patients with non-target lung lesions. However, because the sizes of non-target lesions were either not measurable or not measured, the analysis focused on patients with target lung metastases that could be classified as measurable based on the RECIST v1.1 criterion to evaluate treatment efficacy in relation to size of lung metastases. Patients were grouped by size of the baseline lung metastasis and placed into subgroups: any lung metastases (target/non-target lesions), and maximum size of target lung lesions >1.0 cm, >1.5 cm, >2.0 cm or <2.0 cm.

"At Eisai, we believe it is imperative to continue studying LENVIMA in different patient populations across tumor types," said Dr. Takashi Owa, Vice President, Chief Medicine Creation Officer and Chief Discovery Officer, Oncology Business Group at Eisai. "Analyses like these represent our commitment to continuing to explore, analyze and publish scientific findings for physicians and patients, alike, in advanced cancers."

SELECT enrolled patients with RAI-refractory DTC who had experienced tumor progression within the previous 13 months and, therefore, the results of this post hoc analysis were limited to a patient population with RAI-refractory DTC. In the SELECT study, size of lung metastasis was not a predefined eligibility criterion and was not included as a stratification factor for randomization. Additionally, the impact of the number of lung metastases and non-target lesions on efficacy was not evaluated in this study.

In March 2018, Eisai and Merck (known as MSD outside the United States and Canada), through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA.

About SELECT
The SELECT (Study of E7080 LEnvatinib in Differentiated Cancer of the Thyroid) study was a multicenter, randomized, double-blind, placebo-controlled Phase 3 study to compare the PFS of patients with radioiodine-refractory differentiated thyroid cancer and radiographic evidence of disease progression within the prior 12 months, treated with once-daily, oral lenvatinib (24mg) versus placebo. Secondary endpoints of the study included overall response rate (ORR), overall survival (OS), and safety. The study enrolled 392 patients at over 100 sites in Europe, North and South America and Asia and was conducted by Eisai in collaboration with the SFJ Pharmaceuticals Group.

About Thyroid Cancer
Thyroid cancer is the most common endocrine malignancy and global figures show that its incidence is on the rise. In 2021, it is estimated that there will be 44,280 new cases of thyroid cancer in the U.S. and that women are three times more likely to develop thyroid cancer than men. The most common types of thyroid cancer, papillary and follicular (including Hürthle cell), are classified as DTC and account for approximately 90% of all cases. While most patients with DTC are curable with surgery and radioactive iodine treatment, the prognosis for those patients whose cancers persist or recur is poor.

About LENVIMA (lenvatinib) Capsules
LENVIMA is indicated:

For the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC)
In combination with everolimus for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy
For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)
In combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma, that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy, and are not candidates for curative surgery or radiation. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial
LENVIMA, discovered and developed by Eisai, is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. In syngeneic mouse tumor models, lenvatinib decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Hypertension. In DTC, hypertension occurred in 73% of patients on LENVIMA (44% grade 3-4). In RCC, hypertension occurred in 42% of patients on LENVIMA + everolimus (13% grade 3). Systolic blood pressure ≥160 mmHg occurred in 29% of patients, and 21% had diastolic blood pressure ≥100 mmHg. In HCC, hypertension occurred in 45% of LENVIMA-treated patients (24% grade 3). Grade 4 hypertension was not reported in HCC.

Serious complications of poorly controlled hypertension have been reported. Control blood pressure prior to initiation. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at reduced dose when hypertension is controlled or permanently discontinue based on severity.

Cardiac Dysfunction. Serious and fatal cardiac dysfunction can occur with LENVIMA. Across clinical trials in 799 patients with DTC, RCC, and HCC, grade 3 or higher cardiac dysfunction occurred in 3% of LENVIMA-treated patients. Monitor for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Arterial Thromboembolic Events. Among patients receiving LENVIMA or LENVIMA + everolimus, arterial thromboembolic events of any severity occurred in 2% of patients in RCC and HCC and 5% in DTC. Grade 3-5 arterial thromboembolic events ranged from 2% to 3% across all clinical trials. Permanently discontinue following an arterial thrombotic event. The safety of resuming after an arterial thromboembolic event has not been established, and LENVIMA has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.

Hepatotoxicity. Across clinical studies enrolling 1,327 LENVIMA-treated patients with malignancies other than HCC, serious hepatic adverse reactions occurred in 1.4% of patients. Fatal events, including hepatic failure, acute hepatitis and hepatorenal syndrome, occurred in 0.5% of patients. In HCC, hepatic encephalopathy occurred in 8% of LENVIMA-treated patients (5% grade 3-5). Grade 3-5 hepatic failure occurred in 3% of LENVIMA-treated patients; 2% of patients discontinued LENVIMA due to hepatic encephalopathy, and 1% discontinued due to hepatic failure.

Monitor liver function prior to initiation, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Renal Failure or Impairment. Serious including fatal renal failure or impairment can occur with LENVIMA. Renal impairment was reported in 14% and 7% of LENVIMA-treated patients in DTC and HCC, respectively. Grade 3-5 renal failure or impairment occurred in 3% of patients with DTC and 2% of patients with HCC, including 1 fatal event in each study. In RCC, renal impairment or renal failure was reported in 18% of LENVIMA + everolimus–treated patients (10% grade 3).

Initiate prompt management of diarrhea or dehydration/hypovolemia. Withhold and resume at reduced dose upon recovery or permanently discontinue for renal failure or impairment based on severity.

Proteinuria. In DTC and HCC, proteinuria was reported in 34% and 26% of LENVIMA-treated patients, respectively. Grade 3 proteinuria occurred in 11% and 6% in DTC and HCC, respectively. In RCC, proteinuria occurred in 31% of patients receiving LENVIMA + everolimus (8% grade 3). Monitor for proteinuria prior to initiation and periodically during treatment. If urine dipstick proteinuria ≥2+ is detected, obtain a 24-hour urine protein. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Diarrhea. Of the 737 LENVIMA-treated patients in DTC and HCC, diarrhea occurred in 49% (6% grade 3). In RCC, diarrhea occurred in 81% of LENVIMA + everolimus–treated patients (19% grade 3). Diarrhea was the most frequent cause of dose interruption/reduction, and diarrhea recurred despite dose reduction. Promptly initiate management of diarrhea. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Fistula Formation and Gastrointestinal Perforation. Of the 799 patients treated with LENVIMA or LENVIMA + everolimus in DTC, RCC, and HCC, fistula or gastrointestinal perforation occurred in 2%. Permanently discontinue in patients who develop gastrointestinal perforation of any severity or grade 3-4 fistula.

QT Interval Prolongation. In DTC, QT/QTc interval prolongation occurred in 9% of LENVIMA-treated patients and QT interval prolongation of >500 ms occurred in 2%. In RCC, QTc interval increases of >60 ms occurred in 11% of patients receiving LENVIMA + everolimus and QTc interval >500 ms occurred in 6%. In HCC, QTc interval increases of >60 ms occurred in 8% of LENVIMA-treated patients and QTc interval >500 ms occurred in 2%.

Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold and resume at reduced dose upon recovery based on severity.

Hypocalcemia. In DTC, grade 3-4 hypocalcemia occurred in 9% of LENVIMA-treated patients. In 65% of cases, hypocalcemia improved or resolved following calcium supplementation with or without dose interruption or dose reduction. In RCC, grade 3-4 hypocalcemia occurred in 6% of LENVIMA + everolimus–treated patients. In HCC, grade 3 hypocalcemia occurred in 0.8% of LENVIMA-treated patients. Monitor blood calcium levels at least monthly and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS). Across clinical studies of 1,823 patients who received LENVIMA as a single agent, RPLS occurred in 0.3%. Confirm diagnosis of RPLS with MRI. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity and persistence of neurologic symptoms.

Hemorrhagic Events. Serious including fatal hemorrhagic events can occur with LENVIMA. In DTC, RCC, and HCC clinical trials, hemorrhagic events, of any grade, occurred in 29% of the 799 patients treated with LENVIMA as a single agent or in combination with everolimus. The most frequently reported hemorrhagic events (all grades and occurring in at least 5% of patients) were epistaxis and hematuria. In DTC, grade 3-5 hemorrhage occurred in 2% of LENVIMA-treated patients, including 1 fatal intracranial hemorrhage among 16 patients who received LENVIMA and had CNS metastases at baseline. In RCC, grade 3-5 hemorrhage occurred in 8% of LENVIMA + everolimus–treated patients, including 1 fatal cerebral hemorrhage. In HCC, grade 3-5 hemorrhage occurred in 5% of LENVIMA-treated patients, including 7 fatal hemorrhagic events. Serious tumor-related bleeds, including fatal hemorrhagic events, occurred in LENVIMA-treated patients in clinical trials and in the postmarketing setting. In postmarketing surveillance, serious and fatal carotid artery hemorrhages were seen more frequently in patients with anaplastic thyroid carcinoma (ATC) than other tumors. Safety and effectiveness of LENVIMA in patients with ATC have not been demonstrated in clinical trials.

Consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (eg, carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction. LENVIMA impairs exogenous thyroid suppression. In DTC, 88% of patients had baseline thyroid stimulating hormone (TSH) level ≤0.5 mU/L. In patients with normal TSH at baseline, elevation of TSH level >0.5 mU/L was observed post baseline in 57% of LENVIMA-treated patients. In RCC and HCC, grade 1 or 2 hypothyroidism occurred in 24% of LENVIMA + everolimus–treated patients and 21% of LENVIMA-treated patients, respectively. In patients with normal or low TSH at baseline, elevation of TSH was observed post baseline in 70% of LENVIMA-treated patients in HCC and 60% of LENVIMA + everolimus–treated patients in RCC.

Monitor thyroid function prior to initiation and at least monthly during treatment. Treat hypothyroidism according to standard medical practice.

Impaired Wound Healing. Impaired wound healing has been reported in patients who received LENVIMA. Withhold LENVIMA for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of LENVIMA after resolution of wound healing complications has not been established.

Osteonecrosis of the Jaw (ONJ). ONJ has been reported in patients receiving LENVIMA. Concomitant exposure to other risk factors, such as bisphosphonates, denosumab, dental disease, or invasive dental procedures, may increase the risk of ONJ.

Perform an oral examination prior to treatment with LENVIMA and periodically during LENVIMA treatment. Advise patients regarding good oral hygiene practices and to consider having preventive dentistry performed prior to treatment with LENVIMA and throughout treatment with LENVIMA.

Avoid invasive dental procedures, if possible, while on LENVIMA treatment, particularly in patients at higher risk. Withhold LENVIMA for at least 1 week prior to scheduled dental surgery or invasive dental procedures, if possible. For patients requiring invasive dental procedures, discontinuation of bisphosphonate treatment may reduce the risk of ONJ.

Withhold LENVIMA if ONJ develops and restart based on clinical judgement of adequate resolution.

Embryo-fetal Toxicity. Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to pregnant women. In animal reproduction studies, oral administration of lenvatinib during organogenesis at doses below the recommended clinical doses resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits. Advise pregnant women of the potential risk to a fetus, and advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for at least 30 days after the last dose.

Adverse Reactions
In DTC, the most common adverse reactions (≥30%) observed in LENVIMA-treated patients were hypertension (73%), fatigue (67%), diarrhea (67%), arthralgia/myalgia (62%), decreased appetite (54%), decreased weight (51%), nausea (47%), stomatitis (41%), headache (38%), vomiting (36%), proteinuria (34%), palmar-plantar erythrodysesthesia syndrome (32%), abdominal pain (31%), and dysphonia (31%). The most common serious adverse reactions (≥2%) were pneumonia (4%), hypertension (3%), and dehydration (3%). Adverse reactions led to dose reductions in 68% of LENVIMA-treated patients; 18% discontinued LENVIMA. The most common adverse reactions (≥10%) resulting in dose reductions were hypertension (13%), proteinuria (11%), decreased appetite (10%), and diarrhea (10%); the most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were hypertension (1%) and asthenia (1%).

In RCC, the most common adverse reactions (≥30%) observed in LENVIMA + everolimus–treated patients were diarrhea (81%), fatigue (73%), arthralgia/myalgia (55%), decreased appetite (53%), vomiting (48%), nausea (45%), stomatitis (44%), hypertension (42%), peripheral edema (42%), cough (37%), abdominal pain (37%), dyspnea (35%), rash (35%), decreased weight (34%), hemorrhagic events (32%), and proteinuria (31%). The most common serious adverse reactions (≥5%) were renal failure (11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and dyspnea (5%). Adverse reactions led to dose reductions or interruption in 89% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and proteinuria (5%). Treatment discontinuation due to an adverse reaction occurred in 29% of patients.

In HCC, the most common adverse reactions (≥20%) observed in LENVIMA-treated patients were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%), arthralgia/myalgia (31%), decreased weight (31%), abdominal pain (30%), palmar-plantar erythrodysesthesia syndrome (27%), proteinuria (26%), dysphonia (24%), hemorrhagic events (23%), hypothyroidism (21%), and nausea (20%). The most common serious adverse reactions (≥2%) were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%), and decreased appetite (2%). Adverse reactions led to dose reductions or interruption in 62% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were fatigue (9%), decreased appetite (8%), diarrhea (8%), proteinuria (7%), hypertension (6%), and palmar-plantar erythrodysesthesia syndrome (5%). Treatment discontinuation due to an adverse reaction occurred in 20% of patients. The most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were fatigue (1%), hepatic encephalopathy (2%), hyperbilirubinemia (1%), and hepatic failure (1%).

In EC, the most common adverse reactions (≥20%) observed in LENVIMA + pembrolizumab-treated patients were fatigue (65%), hypertension (65%), musculoskeletal pain (65%), diarrhea (64%), decreased appetite (52%), hypothyroidism (51%), nausea (48%), stomatitis (43%), vomiting (39%), decreased weight (36%), abdominal pain (33%), headache (33%), constipation (32%), urinary tract infection (31%), dysphonia (29%), hemorrhagic events (28%), hypomagnesemia (27%), palmar–plantar erythrodysesthesia (26%), dyspnea (24%), cough (21%), and rash (21%). Adverse reactions led to dose reduction or interruption in 88% of patients receiving LENVIMA. The most common adverse reactions (≥5%) resulting in dose reduction or interruption of LENVIMA were fatigue (32%), hypertension (26%), diarrhea (18%), nausea (13%), palmar–plantar erythrodysesthesia (13%), vomiting (13%), decreased appetite (12%), musculoskeletal pain (11%), stomatitis (9%), abdominal pain (7%), hemorrhages (7%), renal impairment (6%), decreased weight (6%), rash (5%), headache (5%), increased lipase (5%), and proteinuria (5%). Fatal adverse reactions occurred in 3% of patients receiving LENVIMA + pembrolizumab, including gastrointestinal perforation, RPLS with intraventricular hemorrhage, and intracranial hemorrhage. Serious adverse reactions occurred in 52% of patients receiving LENVIMA + pembrolizumab. Serious adverse reactions in ≥3% of patients were hypertension (9%), abdominal pain (6%), musculoskeletal pain (5%), hemorrhage (4%), fatigue (4%), nausea (4%), confusional state (4%), pleural effusion (4%), adrenal insufficiency (3%), colitis (3%), dyspnea (3%), and pyrexia (3%). Permanent discontinuation due to adverse reaction (Grade 1–4) occurred in 21% of patients who received LENVIMA + pembrolizumab. The most common adverse reactions (>2%) resulting in discontinuation of LENVIMA were gastrointestinal perforation or fistula (2%), muscular weakness (2%), and pancreatitis (2%).

Use in Specific Populations
Because of the potential for serious adverse reactions in breastfed infants, advise women to discontinue breastfeeding during treatment and for at least 1 week after the last dose. LENVIMA may impair fertility in males and females of reproductive potential.

No dose adjustment is recommended for patients with mild (CLcr 60-89 mL/min) or moderate (CLcr 30-59 mL/min) renal impairment. LENVIMA concentrations may increase in patients with DTC, RCC, or EC and severe (CLcr 15-29 mL/min) renal impairment. Reduce the dose for patients with DTC, RCC, or EC and severe renal impairment. There is no recommended dose for patients with HCC and severe renal impairment. LENVIMA has not been studied in patients with end-stage renal disease. No dose adjustment is recommended for patients with HCC and mild hepatic impairment (Child-Pugh A). There is no recommended dose for patients with HCC with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment.

No dose adjustment is recommended for patients with DTC, RCC, or EC and mild or moderate hepatic impairment. LENVIMA concentrations may increase in patients with DTC, RCC, or EC and severe hepatic impairment. Reduce the dose for patients with DTC, RCC, or EC and severe hepatic impairment.

LENVIMA (lenvatinib) is available as 10 mg and 4 mg capsules.

Please see Prescribing information for LENVIMA (lenvatinib) at View Source

About the Eisai and Merck Strategic Collaboration
In March 2018, Eisai and Merck, known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with Merck’s anti-PD-1 therapy KEYTRUDA.

In addition to ongoing clinical studies evaluating the KEYTRUDA plus LENVIMA combination across several different tumor types, the companies have jointly initiated new clinical studies through the LEAP (LEnvatinib And Pembrolizumab) clinical program and are evaluating the combination in 14 different tumor types (endometrial carcinoma, hepatocellular carcinoma, melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, urothelial cancer, biliary tract cancer, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer, pancreatic cancer and triple-negative breast cancer) across more than 20 clinical trials.