IGM Biosciences Announces Closing of Initial Public Offering, Including Full Exercise of Underwriters’ Option to Purchase Additional Shares

On September 20, 2019 IGM Biosciences, Inc. (Nasdaq: IGMS) reported the closing of its initial public offering of 12,578,125 shares of its common stock at a price to the public of $16.00 per share, which includes the exercise in full by the underwriters of their option to purchase up to 1,640,625 additional shares (Press release, IGM Biosciences, SEP 20, 2019, View Source [SID1234539668]). The shares began trading on The Nasdaq Global Select Market on September 18, 2019 under the symbol "IGMS." IGM received gross proceeds, before deducting underwriting discounts and commissions and estimated offering expenses, of approximately $201.3 million.

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Jefferies, Piper Jaffray, Stifel and Guggenheim Securities acted as joint book-running managers for the offering.

A registration statement relating to the offering was declared effective by the United States Securities and Exchange Commission on September 17, 2019. The offering was made only by means of a prospectus. A copy of the final prospectus relating to this offering may be obtained from: Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by telephone at (877) 821-7388, or by email at [email protected]; Piper Jaffray & Co, Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, by telephone at (800) 747-3924 or by email at [email protected]; Stifel, Nicolaus & Company, Incorporated, Attention: Syndicate, One Montgomery Street, Suite 3700, San Francisco, CA 94104, by telephone at (415) 364-2720 or by email at [email protected]; or Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison, 8th Floor, New York, NY 10017, by telephone at (212) 518-9658 or by email at [email protected].

This press release does not constitute an offer to sell or a solicitation of an offer to buy, nor will there be any sale of these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful before registration or qualification under the securities laws of that state or jurisdiction.

Aeterna Zentaris Announces Pricing of Approximately $5.0 Million Registered Direct Offering

On September 20, 2019 Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZS), a specialty biopharmaceutical company engaged in commercializing novel pharmaceutical therapies, principally through out-licensing arrangements, reported that it has entered into a securities purchase agreement with institutional investors in the United States to purchase approximately $5.0 million of its common shares in a registered direct offering and warrants to purchase common shares in a concurrent private placement (Press release, AEterna Zentaris, SEP 20, 2019, View Source [SID1234539667]). The combined purchase price for one common share and one warrant will be $1.50.

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Under the terms of the securities purchase agreement, Aeterna has agreed to sell 3,325,000 shares of its common shares. In a concurrent private placement, Aeterna has agreed to issue warrants to purchase up to an aggregate of 3,325,000 common shares. The warrants will be exercisable for a period of 5 years commencing six months from the date of issuance and have an exercise price of $1.65 per share.

The Company expects gross proceeds from the registered direct offering and concurrent private placement to be approximately $5.0 million before deducting placement agent’s fees and expenses. The registered direct offering and concurrent private placement is expected to close on or about September 24, 2019, subject to the satisfaction of customary closing conditions.

Maxim Group LLC is acting as sole placement agent in connection with the offering.

The common shares described above are being offered by Aeterna Zentaris pursuant to a "shelf" registration statement on Form F-3 (File No. 333-232935) previously filed and declared effective by the Securities and Exchange Commission (SEC). The warrants issued in the concurrent private placement and shares issuable upon exercise of such warrants were offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and have not been registered under the Act or applicable state securities law.

This press release does not constitute an offer to sell or the solicitation of an offer to buy, nor will there be any sales of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such jurisdiction. No Canadian prospectus has been or will be filed in a province or territory of Canada to qualify the common shares in connection with the offering. A prospectus supplement relating to the shares of common shares will be filed by Aeterna with the SEC. When available, copies of the prospectus supplement relating to the registered direct offering, together with the accompanying prospectus, can be obtained at the SEC’s website at www.sec.gov or from Maxim Group LLC, 405 Lexington Avenue, New York, NY 10174, Attention: Syndicate Department, or via email at [email protected] or telephone at (212) 895-3745.

TG Therapeutics to Present at the Ladenburg Thalmann Healthcare Conference

On September 20, 2019 TG Therapeutics, Inc. (NASDAQ: TGTX), reported that Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, will present at the Ladenburg Thalmann Healthcare Conference, being held at the Sofitel, in New York City (Press release, TG Therapeutics, SEP 20, 2019, View Source [SID1234539666]). The presentation is scheduled to take place on Tuesday, September 24, 2019 at 11:00 AM ET.

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A live webcast of this presentation will be available on the Events page, located within the Investors & Media section, of the Company’s website at View Source

Taiho Pharmaceutical Obtains Approval of Additional Dosage and Administration for Breast Cancer in Japan for Antitumor Agent ABRAXANE® I.V. Infusion 100 mg

On September 20, 2019 Taiho Pharmaceutical Co., Ltd. reported that an antitumor agent "ABRAXANE I.V. Infusion 100 mg" (paclitaxel protein-bound particles for injectable suspension (albumin-bound); [nab-paclitaxel]), launched in Japan in September 2010, received additional approval for weekly administration*1 in combination with atezolizumab (genetic recombinant) in patients with breast cancer from Japan’s Ministry of Health, Labour and Welfare (Press release, Taiho, SEP 20, 2019, View Source [SID1234539665]).

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ABRAXANE was approved in Japan to treat patients with breast cancer in July 2010, gastric cancer and non-small cell lung cancer in February 2013 and unresectable pancreatic cancer in December 2014. The additional dosage and administration in the breast cancer indication was approved on the basis of a global phase III clinical study (IMpassion130 study) conducted by Chugai Pharmaceutical Co., Ltd. and is in addition to the already approved course of administration every three weeks*2.

The IMpassion130 study is a Phase III, multicentre, double-blind, randomized, placebo-controlled, global clinical study evaluating the efficacy, safety, and pharmacokinetics of atezolizumab in combination with ABRAXANE compared with ABRAXANE plus placebo in patients with unresectable locally advanced or metastatic triple-negative breast cancer who have not received prior systemic therapy for metastatic breast cancer. One of the primary endpoints of this study is progression-free survival (PFS) in the intent-to-treat (ITT) and PD-L1 positive population, statistically significant extension of PFS was shown.*3

About ABRAXANE
ABRAXANE, is albumin-bound nanoparticles of paclitaxel that can be reconstituted with saline solution. It was developed by Abraxis BioScience, LLC and is marketed worldwide by Celgene Corporation, the parent company of Abraxis BioScience, LLC. Taiho Pharmaceutical has the development and marketing rights in Japan. ABRAXANE was initially approved in January 2005 by the U.S. FDA for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. As of January 2019, it has been approved in 74 countries worldwide, including the U.S. and Europe.

About Triple-Negative Breast Cancer
In Japan, 86,500 women (2018 predicted value) are estimated to be afflicted with breast cancer each year, and 14,800 women in Japan (2018 predicted value) die as a result of the disease.*4 Triple-negative breast cancer is defined by the lack of expression of female hormone receptors (estrogen and progesterone receptors) and the overexpression of the HER2 protein and amplification of the HER2 gene, which are involved in cancer cell proliferation. Triple-negative breast cancer accounts for 15% of all breast cancer cases and generally progresses quickly and carries a poor prognosis.

Product Information
Product Name
ABRAXANE I.V. Infusion 100 mg (paclitaxel injection [suspension with albumin])

Indication
Breast cancer, gastric cancer, non-small cell lung cancer and unresectable pancreatic cancer

Dosage and Administration (Newly approved dosage and administration is underlined.)
Either method A or method E*5 should be used for breast cancer; either method A or method D should be used for gastric cancer; method B should be used for non-small cell lung cancer; and method C used for unresectable pancreatic cancer.

Method A: In usual cases, paclitaxel is to be intravenously administered to an adult patient for 30 minutes once a day at 260 mg/m2 (body surface area), followed by a treatment-free interval for at least 20 days.

The treatment cycle above is to be repeated.

Dosage should be reduced based on the patient’s condition.

Method B: In usual cases, paclitaxel is to be intravenously administered to an adult patient for 30 minutes once a day at 100 mg/m2 (body surface area), followed by a treatment-free interval for at least 6 days. The administration is once a week for 3 consecutive weeks, repeating this cycle subsequently. Dosage should be reduced based on the patient’s condition.

Method C: In usual cases, in combination with gemcitabine, paclitaxel is to be intravenously administered to an adult patient for 30 minutes once a day at 125 mg/m2 (body surface area), followed by a treatment-free interval for at least 6 days. The administration is once a week for 3 consecutive weeks followed by a one-week rest. The treatment cycle above is to be repeated. Dosage should be reduced based on the patient’s condition.

Method D: In usual cases, paclitaxel is to be intravenously administered to an adult patient for 30 minutes once a day at 100 mg/m2 (body surface area), followed by a treatment-free interval for at least 6 days. The administration is once a week for 3 consecutive weeks followed by a one-week rest. The treatment cycle above is to be repeated. Dosage should be reduced based on the patient’s condition.

Method E: In usual cases, in combination with atezolizumab (genetic recombinant), paclitaxel is to be intravenously administered to an adult patient for 30 minutes once a day at 100 mg/m2 (body surface area), followed by a treatment-free interval for at least 6 days. The administration is once a week for 3 consecutive weeks followed by a one-week rest. The treatment cycle above is to be repeated. Dosage should be reduced based on the patient’s condition.

*1. Administration once per week is continued for a period of 3 weeks after which there is a treatment-free interval of 1 week, which constitutes a single course. This course may be repeated.

*2. There is a treatment-free interval of at least 20 days after each administration, which constitutes a single course. This course may be repeated.

*3: Source: Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 2018;379:2108-21

*4. "Latest Cancer Statistics," a cancer information service of the National Cancer Center Japan

View Source

*5. A usage and dosage limited to "PD-L1-positive, hormone receptor-negative and HER2-negative inoperable or metastatic breast cancer" which is the indication for atezolizumab

CHMP Adopts Positive Opinion for BAVENCIO® (avelumab) Plus Axitinib for First-Line Treatment of Patients with Advanced Renal Cell Carcinoma

On September 20, 2019 EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany in the US and Canada, and Pfizer Inc. (NYSE: PFE) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending approval of BAVENCIO (avelumab) in combination with axitinib for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC) (Press release, Pfizer, SEP 20, 2019, View Source [SID1234539664]). The opinion was based on positive findings from the Phase III JAVELIN Renal 101 study, which demonstrated a significant extension in median progression-free survival (PFS) and a clinically meaningful improvement in objective response rate (ORR) for the combination across all prognostic risk groups compared with sunitinib.1 The CHMP positive opinion will be reviewed by the European Commission (EC), with a decision anticipated in the fourth quarter of this year. EMD Serono and Pfizer have a global strategic alliance to jointly develop and commercialize BAVENCIO.

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"Today’s positive CHMP opinion is a significant step toward potentially transforming the treatment landscape and bringing much needed options to people living with advanced renal cell carcinoma in Europe. We believe that the combination of BAVENCIO plus axitinib has the potential to help address a significant need for patients with advanced renal cell carcinoma for first-line treatments with a benefit across all prognostic risk groups, and we look forward to a decision from the European Commission," said Luciano Rossetti, Head of Global R&D for EMD Serono.

In 2018, an estimated 136,500 new cases of kidney cancer were diagnosed in Europe, and approximately 54,700 people died from the disease.2 RCC is the most common form of kidney cancer, accounting for about 3% of all cancers in adults.2 Approximately 20% to 30% of patients are first diagnosed with RCC at the advanced stage, and 30% of patients treated for an earlier stage go on to develop metastases.3,4 About half of patients living with advanced RCC do not go on to receive additional treatment after first-line therapy,5,6 for reasons that may include poor performance status or adverse events from their initial treatment.5,7,8 The five-year survival rate for patients with metastatic RCC is approximately 12%.9

"Kidney cancer represents a significant burden in Europe, where incidence rates are among the highest in the world," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "Pfizer has been a leader in the development of kidney cancer treatments for more than a decade, and it is a privilege to continue our efforts to bring a new treatment option to this community."

The U.S. Food and Drug Administration (FDA) approved BAVENCIO in combination with axitinib for the first-line treatment of patients with advanced RCC in May 2019.10 A supplemental application for BAVENCIO in combination with axitinib in unresectable or metastatic RCC was submitted in Japan in January 2019.

About the JAVELIN Renal 101 Study

The Phase III JAVELIN Renal 101 study is a randomized, multicenter, open-label study of BAVENCIO in combination with axitinib in 886 patients with untreated advanced or metastatic RCC. The major efficacy outcome measures were PFS as assessed by a Blinded Independent Central Review (BICR) using RECIST v1.1 and overall survival (OS) in the first-line treatment of patients with advanced RCC who have PD-L1-positive tumors (PD‑L1 expression level ³1%). If PFS was statistically significant in patients with PD-L1-positive tumors, it was then tested in all patients irrespective of PD-L1 expression. PFS based on BICR assessment per RECIST v1.1 and OS irrespective of PD‑L1 expression, objective response, time to response (TTR), duration of response (DOR) and safety are included as secondary endpoints. The study is continuing for OS.

About the JAVELIN Clinical Development Program

The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and more than 10,000 patients evaluated across more than 15 different tumor types. In addition to RCC, these tumor types include gastric/gastro-esophageal junction cancer, head and neck cancer, Merkel cell carcinoma, non-small cell lung cancer and urothelial carcinoma.

About BAVENCIO (avelumab)

BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.11-13 BAVENCIO has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.13-15 In November 2014, EMD Serono and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

BAVENCIO Approved Indication in the US

BAVENCIO (avelumab) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

BAVENCIO Important Safety Information from the US FDA-Approved Label

BAVENCIO can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of pneumonitis, and evaluate suspected cases with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold BAVENCIO for moderate (Grade 2) and permanently discontinue for severe (Grade 3), life-threatening (Grade 4), or recurrent moderate (Grade 2) pneumonitis. Pneumonitis occurred in 1.2% of patients, including one (0.1%) patient with Grade 5, one (0.1%) with Grade 4, and five (0.3%) with Grade 3.

BAVENCIO can cause hepatotoxicity and immune-mediated hepatitis, including fatal cases. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater hepatitis. Withhold BAVENCIO for moderate (Grade 2) immune-mediated hepatitis until resolution and permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) immune-mediated hepatitis. Immune-mediated hepatitis occurred with BAVENCIO as a single agent in 0.9% of patients, including two (0.1%) patients with Grade 5, and 11 (0.6%) with Grade 3.

BAVENCIO in combination with axitinib can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation. Consider more frequent monitoring of liver enzymes as compared to when the drugs are used as monotherapy. Withhold BAVENCIO and axitinib for moderate (Grade 2) hepatotoxicity and permanently discontinue the combination for severe or life-threatening (Grade 3 or 4) hepatotoxicity. Administer corticosteroids as needed. In patients treated with BAVENCIO in combination with axitinib, Grades 3 and 4 increased ALT and AST occurred in 9% and 7% of patients, respectively, and immune-mediated hepatitis occurred in 7% of patients, including 4.9% with Grade 3 or 4.

BAVENCIO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold BAVENCIO until resolution for moderate or severe (Grade 2 or 3) colitis until resolution. Permanently discontinue for life-threatening (Grade 4) or recurrent (Grade 3) colitis upon reinitiation of BAVENCIO. Immune-mediated colitis occurred in 1.5% of patients, including seven (0.4%) with Grade 3.

BAVENCIO can cause immune-mediated endocrinopathies, including adrenal insufficiency, thyroid disorders, and type 1 diabetes mellitus.

Monitor patients for signs and symptoms of adrenal insufficiency during and after treatment, and administer corticosteroids as appropriate. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency. Adrenal insufficiency was reported in 0.5% of patients, including one (0.1%) with Grade 3.

Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation. Manage hypothyroidism with hormone replacement therapy and hyperthyroidism with medical management. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) thyroid disorders. Thyroid disorders, including hypothyroidism, hyperthyroidism, and thyroiditis, were reported in 6% of patients, including three (0.2%) with Grade 3.

Type 1 diabetes mellitus including diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Withhold BAVENCIO and administer antihyperglycemics or insulin in patients with severe or life-threatening (Grade ≥3) hyperglycemia, and resume treatment when metabolic control is achieved. Type 1 diabetes mellitus without an alternative etiology occurred in 0.1% of patients, including two cases of Grade 3 hyperglycemia.

BAVENCIO can cause immune-mediated nephritis and renal dysfunction. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater nephritis. Withhold BAVENCIO for moderate (Grade 2) or severe (Grade 3) nephritis until resolution to Grade 1 or lower. Permanently discontinue BAVENCIO for life-threatening (Grade 4) nephritis. Immune-mediated nephritis occurred in 0.1% of patients.

BAVENCIO can result in other severe and fatal immune-mediated adverse reactions involving any organ system during treatment or after treatment discontinuation. For suspected immune-mediated adverse reactions, evaluate to confirm or rule out an immune-mediated adverse reaction and to exclude other causes. Depending on the severity of the adverse reaction, withhold or permanently discontinue BAVENCIO, administer high-dose corticosteroids, and initiate hormone replacement therapy, if appropriate. Resume BAVENCIO when the immune-mediated adverse reaction remains at Grade 1 or lower following a corticosteroid taper. Permanently discontinue BAVENCIO for any severe (Grade 3) immune-mediated adverse reaction that recurs and for any life-threatening (Grade 4) immune-mediated adverse reaction. The following clinically significant immune-mediated adverse reactions occurred in less than 1% of 1738 patients treated with BAVENCIO as a single agent or in 489 patients who received BAVENCIO in combination with axitinib: myocarditis including fatal cases, pancreatitis including fatal cases, myositis, psoriasis, arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barré syndrome, and systemic inflammatory response.

BAVENCIO can cause severe or life-threatening infusion-related reactions. Premedicate patients with an antihistamine and acetaminophen prior to the first 4 infusions and for subsequent infusions based upon clinical judgment and presence/severity of prior infusion reactions. Monitor patients for signs and symptoms of infusion-related reactions, including pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Interrupt or slow the rate of infusion for mild (Grade 1) or moderate (Grade 2) infusion-related reactions. Permanently discontinue BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Infusion-related reactions occurred in 25% of patients, including three (0.2%) patients with Grade 4 and nine (0.5%) with Grade 3.

BAVENCIO in combination with axitinib can cause major adverse cardiovascular events (MACE) including severe and fatal events. Consider baseline and periodic evaluations of left ventricular ejection fraction. Monitor for signs and symptoms of cardiovascular events. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue BAVENCIO and axitinib for Grade 3-4 cardiovascular events. MACE occurred in 7% of patients with advanced RCC treated with BAVENCIO in combination with axitinib compared to 3.4% treated with sunitinib. These events included death due to cardiac events (1.4%), Grade 3-4 myocardial infarction (2.8%), and Grade 3-4 congestive heart failure (1.8%).

BAVENCIO can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus including the risk of fetal death. Advise females of childbearing potential to use effective contraception during treatment with BAVENCIO and for at least 1 month after the last dose of BAVENCIO. It is not known whether BAVENCIO is excreted in human milk. Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose of BAVENCIO due to the potential for serious adverse reactions in breastfed infants.

Please see full US Prescribing Information and Medication Guide available at View Source

Axitinib Important Safety Information from the US FDA-Approved Label

Hypertension including hypertensive crisis has been observed with axitinib. Blood pressure should be well controlled prior to initiating axitinib. Monitor for hypertension and treat as needed. For persistent hypertension, despite use of antihypertensive medications, reduce the dose. Discontinue axitinib if hypertension is severe and persistent despite use of antihypertensive therapy and dose reduction of axitinib, and discontinuation should be considered if there is evidence of hypertensive crisis.

Arterial and venous thrombotic events have been observed with axitinib and can be fatal. Use with caution in patients who are at increased risk or who have a history of these events.

Hemorrhagic events, including fatal events, have been reported with axitinib. Axitinib has not been studied in patients with evidence of untreated brain metastasis or recent active gastrointestinal bleeding and should not be used in those patients. If any bleeding requires medical intervention, temporarily interrupt the axitinib dose.

Cardiac failure has been observed with axitinib and can be fatal. Monitor for signs or symptoms of cardiac failure throughout treatment with axitinib. Management of cardiac failure may require permanent discontinuation of axitinib.

Gastrointestinal perforation and fistula, including death, have occurred with axitinib. Use with caution in patients at risk for gastrointestinal perforation or fistula. Monitor for symptoms of gastrointestinal perforation or fistula periodically throughout treatment.

Hypothyroidism requiring thyroid hormone replacement has been reported with axitinib. Monitor thyroid function before initiation of, and periodically throughout, treatment.

No formal studies of the effect of axitinib on wound healing have been conducted. Stop axitinib at least 24 hours prior to scheduled surgery.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has been observed with axitinib. If signs or symptoms occur, permanently discontinue treatment.

Proteinuria has been observed with axitinib. Monitor for proteinuria before initiation of, and periodically throughout, treatment with axitinib. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment.

Liver enzyme elevation has been observed during treatment with axitinib. Monitor ALT, AST, and bilirubin before initiation of, and periodically throughout, treatment.

For patients with moderate hepatic impairment, the starting dose should be decreased. Axitinib has not been studied in patients with severe hepatic impairment.

Axitinib can cause fetal harm. Advise patients of the potential risk to the fetus and to use effective contraception during treatment.

Avoid strong CYP3A4/5 inhibitors. If unavoidable, reduce the dose. Grapefruit or grapefruit juice may also increase axitinib plasma concentrations and should be avoided.

Avoid strong CYP3A4/5 inducers and, if possible, avoid moderate CYP3A4/5 inducers.

Please see full Prescribing Information for axitinib.

ADVERSE REACTIONS (BAVENCIO + AXITINIB)

Fatal adverse reactions occurred in 1.8% of patients with advanced renal cell carcinoma (RCC) receiving BAVENCIO in combination with axitinib. These included sudden cardiac death (1.2%), stroke (0.2%), myocarditis (0.2%), and necrotizing pancreatitis (0.2%).

The most common adverse reactions (all grades, ≥20%) in patients with advanced RCC receiving BAVENCIO in combination with axitinib (vs sunitinib) were diarrhea (62% vs 48%), fatigue (53% vs 54%), hypertension (50% vs 36%), musculoskeletal pain (40% vs 33%), nausea (34% vs 39%), mucositis (34% vs 35%), palmar-plantar erythrodysesthesia (33% vs 34%), dysphonia (31% vs 3.2%), decreased appetite (26% vs 29%), hypothyroidism (25% vs 14%), rash (25% vs 16%), hepatotoxicity (24% vs 18%), cough (23% vs 19%), dyspnea (23% vs 16%), abdominal pain (22% vs 19%), and headache (21% vs 16%).

Selected laboratory abnormalities (all grades, ≥20%) worsening from baseline in patients with advanced RCC receiving BAVENCIO in combination with axitinib (vs sunitinib) were blood triglycerides increased (71% vs 48%), blood creatinine increased (62% vs 68%), blood cholesterol increased (57% vs 22%), alanine aminotransferase increased (ALT) (50% vs 46%), aspartate aminotransferase increased (AST) (47% vs 57%), blood sodium decreased (38% vs 37%), lipase increased (37% vs 25%), blood potassium increased (35% vs 28%), platelet count decreased (27% vs 80%), blood bilirubin increased (21% vs 23%), and hemoglobin decreased (21% vs 65%).

The most common adverse reactions (all grades, ≥20%) in patients with advanced RCC receiving BAVENCIO in combination with axitinib (vs sunitinib) were diarrhea (62% vs 48%), fatigue (53% vs 54%), hypertension (50% vs 36%), musculoskeletal pain (40% vs 33%), nausea (34% vs 39%), mucositis (34% vs 35%), palmar-plantar erythrodysesthesia (33% vs 34%), dysphonia (31% vs 3.2%), decreased appetite (26% vs 29%), hypothyroidism (25% vs 14%), rash (25% vs 16%), hepatotoxicity (24% vs 18%), cough (23% vs 19%), dyspnea (23% vs 16%), abdominal pain (22% vs 19%), and headache (21% vs 16%).

Selected laboratory abnormalities (all grades, ≥20%) worsening from baseline in patients with advanced RCC receiving BAVENCIO in combination with axitinib (vs sunitinib) were blood triglycerides increased (71% vs 48%), blood creatinine increased (62% vs 68%), blood cholesterol increased (57% vs 22%), alanine aminotransferase increased (ALT) (50% vs 46%), aspartate aminotransferase increased (AST) (47% vs 57%), blood sodium decreased (38% vs 37%), lipase increased (37% vs 25%), blood potassium increased (35% vs 28%), platelet count decreased (27% vs 80%), blood bilirubin increased (21% vs 23%), and hemoglobin decreased (21% vs 65%).