PRINCETON, N.J., May 17, 2016 –(BUSINESS WIRE)–Bristol-Myers Squibb Company (NYSE:BMY) today announced the U.S. Food and Drug Administration (FDA) has approved Opdivo (nivolumab) for the treatment of patients with classical Hodgkin lymphoma (cHL) who have relapsed or progressed after autologous hematopoietic stem cell transplantation (auto-HSCT) and post-transplantation brentuximab vedotin.1 This accelerated approval is based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. This first approval of a PD-1 inhibitor for cHL patients who have relapsed or progressed after auto-HSCT and post-transplantation brentuximab vedotin is based on a combined analysis of data from the Phase 2 CheckMate -205 and the Phase 1 CheckMate -039 trials.1 Based on this analysis (n=95), Opdivo delivered a high response rate, with an objective response rate (ORR) of 65% (CI 95%: 55-75; 62/95 patients).1 The percentage of patients with a complete response was 7% (CI 95%: 3-15; 7/95 patients), and the percentage of patients with a partial response was 58% (CI 95%: 47-68; 55/95 patients).1 Among responders, the duration of response was maintained over time for a median of 8.7 months (CI 95%: 6.8-NE; range 0.0+, 23.1+).1
Opdivo is associated with the following Warnings and Precautions including immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, rash, encephalitis, other adverse reactions; infusion reactions; complications of allogeneic HSCT after Opdivo; and embryo-fetal toxicity.1
“As a classical Hodgkin lymphoma patient who has tried multiple therapies, I know firsthand what it’s like to not have a clear next step,” said Matt Kludt, a patient enrolled in a nivolumab clinical trial. “When I started on Opdivo, I was hopeful about the potential for this new treatment. Now, I’m proud to be able to say I was one of several patients who have helped contribute to the approval of a new therapy that may offer other patients like me the possibility of a high response rate.”
“Today’s approval of Opdivo delivers a transformational and exciting new option for these patients and the hematologists who treat them. By expanding this Immuno-Oncology therapy into a hematologic malignancy, we continue to deliver upon our unwavering commitment to provide treatments that work directly with the body’s immune system for patients who are in need of new options,” said Chris Boerner, Head of U.S. Commercial, Bristol-Myers Squibb. “This is our second Immuno-Oncology agent in blood cancer in less than a year for patients impacted by diseases with a deep unmet need. This approval of Opdivo represents how we are continually working towards the goal of helping patients, like Matt, by offering them a new chance in their fight against this disease.”
The efficacy of Opdivo in patients (n=95) with cHL after failure of auto-HSCT and post-transplantation brentuximab vedotin was evaluated in the combined analysis from two studies.1 CheckMate -205 is a Phase 2, single-arm, open-label, multicenter, multicohort study.1 The results of this trial will be presented at the American Society of Clinical Oncology Annual Meeting in June 2016. CheckMate -039 is a Phase 1, open-label, multicenter, dose escalation study.1 In the combined analysis, efficacy was evaluated by ORR, and an additional outcome measure was duration of response. Objective response rate was assessed by an independent radiographic review committee.1
Both studies excluded patients with an Eastern Cooperative Oncology Group (ECOG) performance status of two or higher, autoimmune disease, symptomatic interstitial lung disease, hepatic transaminases more than three times the upper limit of normal (ULN), creatinine clearance less than 40 mL/min, prior allogeneic HSCT or chest irradiation within 24 weeks.1 In addition, both studies required an adjusted diffusion capacity of the lungs for carbon monoxide (DLCO) of more than 60% in patients with prior pulmonary toxicity.1 Patients received 3 mg/kg of single-agent Opdivo administered as an intravenous infusion over 60 minutes every two weeks until disease progression, maximal clinical benefit or unacceptable toxicity.1
The median age was 37 years (range: 18-72), and the majority were male (64%) and white (87%).1 Patients had received a median of five prior systemic regimens (range: 3-15) and received a median of 17 doses of Opdivo (range: 3-48), with a median duration of therapy of 8.3 months (range: 1.9-24 months).1 In adults with cHL who have relapsed or progressed after auto-HSCT and post-transplantation brentuximab vedotin (n=95), Opdivo demonstrated impressive response rates: ORR was 65% (CI 95%: 55-75; 62/95 patients), including a 7% complete response rate (CI 95%: 3-15; 7/95 patients) and a 58% partial response rate (CI 95%: 47-68; 55/95 patients).1 The median time to response was 2.1 months (range: 0.7-5.7).1 Among responders, Opdivo demonstrated an 8.7 month median duration of response (95% CI: 6.8-NE; range 0.0+, 23.1+).1
The safety of Opdivo in cHL was evaluated in 263 adult patients from the CheckMate -205 (n=240) and -039 (n=23) trials.1 Among these patients (safety population: n=263) serious adverse reactions occurred in 21% of patients.1 The most frequent serious adverse reactions reported in ≥1% of patients were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash and pneumonitis.1 Ten patients died from causes other than disease progression, including 6 who died from complications of allogeneic HSCT.1 In the safety population, 4.2% discontinued treatment due to adverse reactions, and 23% of patients had a dose delay for an adverse reaction.1 In the subset of patients in the efficacy population (n=95), serious adverse reactions occurred in 27% of the patients.1 In CheckMate -205 and -039, among all patients (safety population: n=263) and the subset of patients in the efficacy population (n=95), respectively, the most common adverse reactions (reported in at least 20%) were fatigue (32% and 43%), upper respiratory tract infection (28% and 48%), pyrexia (24% and 35%), diarrhea (23% and 30%), and cough (22% and 35%).1 In the subset of patients in the efficacy population (n=95), the most common adverse reactions also included rash (31%), musculoskeletal pain (27%), pruritus (25%), nausea (23%), arthralgia (21%), and peripheral neuropathy (21%).1
“It is important to have new treatment options for patients with difficult-to-treat diseases who have exhausted the current available options. Because of the unique pathology and biology of classical Hodgkin lymphoma,2 it makes sense from a scientific standpoint to investigate a PD-1 inhibitor,” said Anas Younes, M.D., medical oncologist and chief of Lymphoma Service, Memorial Sloan Kettering Cancer Center. “The recent clinical data with Opdivo in patients with classical Hodgkin lymphoma who have relapsed or progressed after auto-HSCT and post-transplantation brentuximab vedotin is encouraging and has the potential to impact our approach to treating these individuals in the future.”
About Classical Hodgkin Lymphoma
Hodgkin lymphoma (HL), also known as Hodgkin disease, is a cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system.3 Approximately 8,500 new cases of HL are estimated to be diagnosed in 2016.3 More than 1,100 deaths from HL are expected this year. According to the Lymphoma Research Foundation, cHL is the most common type of HL, accounting for 95% of cases.4 In this type of HL, cancer cells are called Reed-Sternberg cells, an abnormal type of B lymphocyte.3
Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, we have a vision for the future of cancer care that is focused on Immuno-Oncology, now considered a major treatment modality alongside surgery, radiation and chemotherapy for certain types of cancer.
We have a comprehensive clinical portfolio of investigational and approved Immuno-Oncology agents, many of which were discovered and developed by our scientists. We pioneered the research leading to the first regulatory approval for the combination of two Immuno-Oncology agents and continue to study the role of combinations in cancer.
Our collaboration with academia as well as small and large biotech companies is responsible for researching the potential Immuno-Oncology and non-Immuno-Oncology combinations, with the goal of providing new treatment options in clinical practice.
At Bristol-Myers Squibb, we are committed to changing expectations in hard-to-treat cancers and the way patients live with cancer.
About Bristol-Myers Squibb’s Access Support
Bristol-Myers Squibb is committed to helping patients access Opdivo and offers BMS Access Support® to support patients and providers in gaining access. BMS Access Support, the Bristol-Myers Squibb Reimbursement Services program, is designed to support access to BMS medicines and expedite time to therapy through reimbursement support including Benefit Investigations, Prior Authorization Facilitation, Appeals Assistance, and assistance for patient out-of-pocket costs. BMS Access Support assists patients and providers throughout the treatment journey – whether it is at initial diagnosis or in support of transition from a clinical trial. More information about our reimbursement support services can be obtained by calling 1-800-861-0048 or by visiting www.bmsaccesssupport.com. For healthcare providers seeking specific reimbursement information, please visit the BMS Access Support Product section by visiting www.bmsaccesssupportopdivo.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 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, and YouTube.
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, 2015 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.
1. Opdivo Prescribing Information. Opdivo U.S. Product Information. Last updated: April 14, 2016. Princeton, NJ: Bristol-Myers Squibb Company.
2. Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin’s Lymphoma. N Engl J Med. 2015;372(4):311-9.
3. American Cancer Society. Hodgkin Disease. http://www.cancer.org/acs/groups/cid/documents/webcontent/003105-pdf.pdf. Updated February 9, 2016. Accessed May 16, 2016.
4. Lymphoma Research Foundation. Hodgkin Lymphoma (HL). http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300137. Accessed May 16, 2016.
OPDIVO, YERVOY and Access Support are trademarks of Bristol-Myers Squibb Company. Other brands listed are the trademarks of their respective owners.
Source: Bristol-Myers Squibb Company
Posted: May 2016
- Bristol-Myers Squibb’s Opdivo (nivolumab) + Yervoy (ipilimumab) Regimen Receives Expanded FDA Approval in Unresectable or Metastatic Melanoma Across BRAF Status – January 23, 2016
- FDA Approves Opdivo to Treat Metastatic Renal Cell Carcinoma – November 23, 2015
- FDA Expands Approved Use of Opdivo (nivolumab) in Advanced Lung Cancer – October 9, 2015
- BMS Receives FDA Approval for Opdivo (nivolumab) + Yervoy (ipilimumab) Regimen in BRAF V600 Wild-Type Melanoma – October 1, 2015
- FDA Expands Approved use of Opdivo (nivolumab) to Treat Lung Cancer – March 4, 2015
- FDA Approves Opdivo (nivolumab) for Advanced Melanoma – December 22, 2014
- Opdivo (nivolumab) Demonstrates High Overall Response Rate of 87% for Treatment of Relapsed or Refractory Hodgkin Lymphoma – December 6, 2014
- Study Comparing Opdivo (nivolumab) to Chemotherapy Demonstrates Survival Benefit – November 16, 2014
- Phase 2 Objective Response Rate and Survival Data for Opdivo (nivolumab) in NSCLC to be Presented – October 30, 2014
- BMS Announces Collaboration to Evaluate Opdivo (nivolumab) in Combination to Treat Non-Small Cell Lung Cancer – October 6, 2014
- Bristol-Myers Squibb Announces Multiple Regulatory Milestones for Opdivo (nivolumab) – September 26, 2014
Source: FDA New Drug Approvals