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Bristol-Myers Squibb’s Opdivo (nivolumab) Receives FDA Approval for the Treatment of Hepatocellular Carcinoma Patients Previously Treated with Sorafenib

PRINCETON, N.J.--(BUSINESS WIRE) September 22, 2017 --Bristol-Myers Squibb Company (NYSE:BMY) today announced the U.S. Food and Drug Administration (FDA) has approved Opdivo (nivolumab) injection for intravenous use for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. Approval for this indication has been granted 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 trials.1 In the CheckMate -040 trial, 14.3%* (95% CI: 9.2-20.8; 22/154) of patients responded to treatment with Opdivo. The percentage of patients with a complete response was 1.9% (3/154) and the percentage of patients with a partial response was 12.3% (19/154).1 Among responders (n=22), responses ranged from 3.2 to 38.2+ months; 91% of those patients had responses of six months or longer and 55% had responses of 12 months or longer.1

Opdivo is associated with the following Warnings and Precautions including: immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions; infusion reactions; and embryo-fetal toxicity.1

“We are proud to bring the potential for clinically meaningful responses with Immuno-Oncology therapy to these advanced-stage HCC patients, who have had limited treatment options for years,” said Chris Boerner, president, U.S. Commercial, Bristol-Myers Squibb. “Today’s approval marks an important step toward our mission of delivering transformational medicines to treat conditions with a high unmet need.”

The burden of liver cancer in the U.S. is significant and is expected to increase in the decades to come.5,6 A recently-released American Cancer Society (ACS) report published in CA: A Cancer Journal for Clinicians notes that death rates for liver cancer are increasing at a faster pace than any other cancer, doubling since the mid-1980s.5

“Unfortunately, the majority of HCC patients are diagnosed with advanced-stage disease and are not candidates for potentially curative surgical interventions,” said Adrian M. Di Bisceglie, M.D., co-director, Saint Louis University Liver Center, Chief of Hepatology. “More options are needed for advanced-stage HCC patients who have failed prior systemic therapy.”

Hepatocellular carcinoma is often diagnosed in the advanced-stage where treatment options are limited and there is a high unmet need for patients who are intolerant to or who have progressed on sorafenib therapy.5,7,8

“In recent years, there has been growing interest in leveraging immuno-oncology knowledge and discoveries to add to the treatment options available for patients with advanced-stage liver cancer,” said Anthony B. El-Khoueiry, M.D., lead investigator and associate professor of clinical medicine and phase I program director at the Keck School of Medicine of University of Southern California (USC) and the USC Norris Comprehensive Cancer Center. “The approval of Opdivo provides us with an encouraging approach and a new treatment option for appropriate patients with HCC following prior systemic therapy.”

Approval Based on Notable Overall Response Rate and Duration of Response

CheckMate -040 included a Phase 1/2, open-label, multicenter study evaluating Opdivo in patients with HCC who progressed on or were intolerant to sorafenib.1,9 In this study, 154 patients received Opdivo 3 mg/kg administered intravenously every two weeks. The recommended dose is 240 milligrams administered as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity.1 Efficacy outcome measures included confirmed overall response rate (as assessed by blinded independent central review using RECIST v1.1 and modified RECIST for HCC) and duration of response.1 The median age of patients participating in the study was 63 (range: 19-81), all patients had received prior sorafenib therapy and 19% of patients had received two or more prior systemic therapies.1 Patients were enrolled regardless of PD-L1 expression level and whether or not they were infected with active Hepatitis B virus (HBV) or active Hepatitis C virus (HCV).1,2 Data from CheckMate -040 were presented at the American Society of Clinical Oncology 2017 Annual Meeting in June.

In the CheckMate -040 trial, 14.3%* (95% CI: 9.2-20.8; 22/154) of patients responded to treatment with Opdivo. The percentage of patients with a complete response was 1.9% (3/154) and the percentage of patients with a partial response was 12.3% (19/154). Among responders (n=22), responses ranged from 3.2 to 38.2+ months; 91% of those patients had responses of six months or longer and 55% had responses of 12 months or longer.1 The median time to response was 2.8 months (range: 1.2-7.0).2 The overall response rate based on modified RECIST was 18.2% (95% CI: 12.4-25.2; 28/154). Complete response rate was 3.2% (5/154); partial response rate was 14.9% (23/154).1 Responses were observed across PD-L1 expression levels.2

“I advocate for others because I know firsthand the terrible toll cancers of the liver take on a patient and their loved ones. In my opinion, HCC is an example of a cancer where awareness is out of sync with the impact of the disease,” said Suzanne Lindley, Co-Founder, Yes! Beat Liver Tumors. “Today’s approval shines a light of awareness and hope on a disease with a high unmet medical need.”

Select Safety Profile

The safety of Opdivo was evaluated in a 154-patient subgroup of patients with HCC and Child-Pugh A cirrhosis who progressed on or were intolerant to sorafenib in the CheckMate -040 study. Patients were required to have an aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of no more than five times the upper limit of normal and total bilirubin of less than 3 mg/dL. The median duration of exposure to Opdivo was six months. Treatment with Opdivo resulted in treatment-emergent Grade 3 or 4 AST in 18% (27/154) of patients, Grade 3 or 4 ALT in 11% (16/154) of patients, and Grade 3 or 4 bilirubin in 7% (11/154) of patients. Immune-mediated hepatitis requiring systemic corticosteroids occurred in 5% (8/154) of patients.1 Serious adverse reactions occurred in 49% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pyrexia, ascites, back pain, general physical health deterioration, abdominal pain, and pneumonia. The most common adverse reactions (≥20%) in patients receiving Opdivo (n=154) were fatigue (38%), musculoskeletal pain (36%), abdominal pain (34%), pruritus (27%), diarrhea (27%), rash (26%), cough (23%), and decreased appetite (22%). Opdivo was discontinued due to adverse reactions in 11% of patients and 32% of patients had a dose delay for an adverse reaction.2

About Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the fastest-growing cause of cancer death in the U.S.3,5,10 The incidence of liver cancer in the U.S. has more than tripled since 1980.3 It is estimated that there will be approximately 41,000 new cases of liver and intrahepatic bile duct cancer and 29,000 deaths from these diseases in the U.S. this year.4 The majority of these cases are caused by Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infections, making chronic infection with HBV or HCV the most common risk factor for liver cancer.10,11 However, the increasing prevalence of metabolic syndrome and nonalcoholic steatohepatitis (NASH) is expected to contribute to increased rates of HCC in the U.S. in the foreseeable future.12,13

About the Opdivo Clinical Development Program

Bristol-Myers Squibb’s global development program is founded on scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials studying Opdivo, across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients.

About Bristol-Myers Squibb’s Patient Access Support

Bristol-Myers Squibb remains committed to providing assistance so that cancer patients who need our medicines can access them and expedite time to therapy.

BMS Access Support®, the Bristol-Myers Squibb patient access and reimbursement services program, is designed to help appropriate patients initiate and maintain access to BMS medicines during their treatment journey. BMS Access Support offers benefit investigation, prior authorization assistance and co-pay assistance for eligible, commercially insured patients. More information about our access and reimbursement support services can be obtained by calling BMS Access Support® at 1-800-861-0048 or by visiting www.bmsaccesssupport.com.

About the Bristol-Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol-Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

About Bristol-Myers Squibb

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 and Facebook.

Bristol-Myers Squibb Forward-Looking Statement

This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb’s business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2016 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

* BICR-assessed based on RECIST v1.1

References

  1. Opdivo Prescribing Information. Opdivo U.S. Product Information. Last updated: September 22, 2017. Princeton, NJ: Bristol-Myers Squibb Company.
  2. Data on file. NIVO 314. Princeton, NJ: Bristol-Myers Squibb.
  3. American Cancer Society. Cancer Facts & Figures. 2017. Atlanta: American Cancer Society; 2017.
  4. National Cancer Institute. Surveillance, Epidemiology, and End Results Program Stat Fact Sheets: Liver and Intrahepatic Bile Duct Cancer. https://seer.cancer.gov/statfacts/html/livibd.html. Accessed July 31, 2017.
  5. Islami F, Miller K, Siegel R, et al. Disparities in Liver Cancer Occurrence in the United States by Race/Ethnicity and State. Ca Cancer J Clin 2017 Jul 8;67(4):273–289.
  6. Wang S, Sun H, Xie Z, et al. Improved survival of patients with hepatocellular carcinoma and disparities by age, race, and socioeconomic status by decade, 1983-2012. Oncotarget. 2016 Sep 13;7(37):59820-59833.
  7. Allaire M and Nault JC. Advances in management of hepatocellular carcinoma. Curr Opin Oncol. 2017 Jul;29(4):288-295.
  8. Mlynarsky L, Menachem Y and Shibolet O. Treatment of hepatocellular carcinoma: Steps forward but still a long way to go. World J Hepatol. 2015 Mar 27;7(3):566-74.
  9. Clinicaltrials.gov. “An Immuno-therapy Study to Evaluate the Effectiveness, Safety and Tolerability of Nivolumab or Nivolumab in Combination With Other Agents in Patients With Advanced Liver Cancer (CheckMate040). Available at: https://clinicaltrials.gov/ct2/show/NCT01658878
  10. Mittal S and El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013 Jul; 47 Suppl:S2-6.
  11. American Cancer Society. Liver Cancer Risk Factors. https://www.cancer.org/cancer/liver-cancer/causes-risks-prevention/risk-factors.html. Accessed August 8, 2017.
  12. Dhanasekaran R, Limaye A and Cabrera R. Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis, and therapeutics. Hepat Med. 2012 May 8;4:19-37.
  13. Yang JD and Roberts LR. Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol. 2010 Aug; 7(8):448-58.

Source: Bristol-Myers Squibb Company

Posted: September 2017

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