Press Release
Press Release
Exelixis Submits U.S. Supplemental New Drug Application for CABOMETYX® (Cabozantinib) for Previously Treated Advanced Hepatocellular Carcinoma
– In the pivotal phase 3 CELESTIAL trial, CABOMETYX provided a statistically significant and clinically meaningful improvement versus placebo in overall survival (OS) –
“We look forward to working closely with regulatory authorities through
the review process in anticipation of bringing CABOMETYX to people
diagnosed with advanced hepatocellular carcinoma, an underserved patient
community that urgently needs new treatment options,” said
On
An sNDA is an application to the
About the CELESTIAL Study
CELESTIAL is a randomized,
double-blind, placebo-controlled study of cabozantinib in patients with
advanced HCC conducted at more than 100 sites globally in 19 countries.
The trial was designed to enroll 760 patients with advanced HCC who
received prior sorafenib and may have received up to two prior systemic
cancer therapies for HCC and had adequate liver function. Enrollment of
the trial was completed in
About HCC
Liver cancer is the second-leading cause of cancer
death worldwide, accounting for more than 700,000 deaths and nearly
800,000 new cases each year.1 In the U.S., the incidence of
liver cancer has more than tripled since 1980.2 HCC is the
most common form of liver cancer, making up about three-fourths of the
estimated nearly 42,000 new cases in the U.S. in 2018.2 HCC
is the fastest-rising cause of cancer-related death in U.S.3
Without treatment, patients with advanced HCC usually survive less than
6 months.4
About CABOMETYX® (cabozantinib)
CABOMETYX
tablets are approved in
CABOMETYX is not indicated for previously treated advanced HCC.
Please see Important Safety Information below and full U.S. prescribing information at https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
U.S. Important Safety Information
- Hemorrhage: Severe and fatal hemorrhages have occurred with CABOMETYX. In two RCC studies, the incidence of Grade ≥ 3 hemorrhagic events was 3% in CABOMETYX-treated patients. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
- Gastrointestinal (GI) Perforations and Fistulas: In RCC studies, fistulas were reported in 1% of CABOMETYX-treated patients. Fatal perforations occurred in patients treated with CABOMETYX. In RCC studies, gastrointestinal (GI) perforations were reported in 1% of CABOMETYX-treated patients. Monitor patients for symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula which cannot be appropriately managed or a GI perforation.
- Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. In RCC studies, venous thromboembolism occurred in 9% (including 5% pulmonary embolism) and arterial thromboembolism occurred in 1% of CABOMETYX-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.
- Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension, including hypertensive crisis. In RCC studies, hypertension was reported in 44% (18% Grade ≥ 3) of CABOMETYX-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.
- Diarrhea: In RCC studies, diarrhea occurred in 74% of patients treated with CABOMETYX. Grade 3 diarrhea occurred in 11% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose.
- Palmar-Plantar Erythrodysesthesia (PPE): In RCC studies, palmar-plantar erythrodysesthesia (PPE) occurred in 42% of patients treated with CABOMETYX. Grade 3 PPE occurred in 8% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPE or Grade 3 PPE until improvement to Grade 1; resume CABOMETYX at a reduced dose.
- Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
- Embryo-fetal Toxicity may be associated with CABOMETYX. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during CABOMETYX treatment and for 4 months after the last dose.
- Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, hypertension, PPE, weight decreased, vomiting, dysgeusia, and stomatitis.
- Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
- Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
- Lactation: Advise women not to breastfeed while taking CABOMETYX and for 4 months after the final dose.
- Hepatic Impairment: In patients with mild to moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.
Please see accompanying full Prescribing Information https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
About
Founded in 1994,
Exelixis Forward-Looking Statement Disclaimer
This press
release contains forward-looking statements, including, without
limitation, statements related to: the regulatory review process;
Exelixis’ goal of expanding the population of patients who might benefit
from CABOMETYX and the potential to bring CABOMETYX to patients
diagnosed with advanced HCC; the therapeutic potential of CABOMETYX as a
treatment for patients with advanced HCC; Exelixis’ plans to reinvest in
its business to maximize the potential of the company’s pipeline,
including through targeted business development activities and internal
drug discovery; and Exelixis’ mission to deliver the next generation of
References:
1 Cancer Incidence and Mortality Worldwide.
Liver Cancer.
2
3 Mittal S, El-Serag HB.
Epidemiology of HCC: Consider the Population.
4 Weledji E, Orock
G, Ngowe M, NsaghaD. How grim is hepatocellular carcinoma? Annals of
Medicine and Surgery. 2014. 3:71-76.
View source version on businesswire.com: http://www.businesswire.com/news/home/20180315005365/en/
Source:
Exelixis, Inc.
Investors:
Susan
Hubbard, 650-837-8194
EVP, Public Affairs and Investor
Relations
shubbard@exelixis.com
or
Media:
Lindsay
Treadway, 650-837-7522
Senior Director, Public Affairs and
Advocacy Relations
ltreadway@exelixis.com