From Bristol-Myers Squibb:

How to Define Value: Patient Outcomes or Modeling?

Bristol-Myers Squibb’s Response to ICER’s Report,“Treatment Options for Relapsed or Refractory Multiple Myeloma: Effectiveness, Value, and Value-based Price Benchmarks”

Thursday, May 26, 2016 10:55 am EDT

At Bristol-Myers Squibb, we are committed to putting patients and their families first in their fight against serious diseases. Through our pioneering Immuno-Oncology research, we are transforming the way cancer is treated and expanding our approach to provide meaningful, long-term outcomes.  It is essential that the healthcare community continues to foster an environment of innovation in order to fulfill the promise of Immuno-Oncology therapies: longer survival and enhanced quality of life for patients and their families. This is particularly important in cancers with a high unmet need, such as relapsed or refractory multiple myeloma.

Today only 49% of multiple myeloma patients survive for five or more years after diagnosis.  Many of these patients experience a cycle of remission and relapse, and once a patient first relapses, their prognosis worsens with progressively faster relapses through each subsequent line of therapy. That is why we have focused on leveraging our Immuno-Oncology science to bring Empliciti™ (elotuzumab) to multiple myeloma patients most in need of new options. Empliciti in combination with Revlimid^®(lenalidomide) and dexamethasone provides multiple myeloma patients who do not respond to, or relapse on their current therapies, a fundamentally different treatment approach by directly activating their own immune systems to fight the disease.

Empliciti has demonstrated clinical effectiveness for patients fighting multiple myeloma, and its breakthrough therapy designation with the U.S. Food and Drug Administration speaks to the unmet need it was designed to help address. However, when discussingEmpliciti’s value in “Treatment Options for Relapsed or Refractory Multiple Myeloma: Effectiveness, Value, and Value-based Price Benchmarks,” the Institute for Clinical and Economic Review (ICER) fails to recognize the patient perspective and the value Emplicitiand other novel therapies may bring to people with relapsed or refractory multiple myeloma and the healthcare system that serves them.

In the spirit of putting patient needs first, we fundamentally disagree with ICER’s approach to value assessment, which led to the questionable conclusions outlined in its report. Our view is based on the following points:

• The report does not reflect the true value of health outcomes in cancer care: With the application of cost-effectiveness thresholds, ICER has imposed arbitrary barriers to patient access. Well-known limitations of quality-adjusted life years (QALY) as a measure of benefit might result in the undervaluing of treatment benefits in older populations—a salient point in multiple myeloma given a median age at diagnosis of 69. Thus, drawing conclusions using ICER’s cost-effectiveness threshold approach risks denying patients access to life-saving cancer treatments that are now the standard of care.
• It is based on uncertainties in comparative effectiveness research: The ICER model exhibits a number of limitations that even the organization itself acknowledges. These include (i) inaccurate and incomplete assessments of costs and cost savings for each therapy, (ii) use of immature data that does not capture potential changes in efficacy that could occur after longer-term patient follow-up, (iii) differences between clinical trials and real-world dosing regimens, (iv) availability of evidence for all relevant treatments and (v) uncertainty of the point estimates. Moreover, ICER’s own analyses have produced highly inconsistent results between the draft and revised versions of the report, thus illustrating the uncertainty of these results.
• It does not adhere to established Health Technology Assessment best practices: Health Technology Assessments should be based on a clear, transparent, sophisticated and differentiated view of what constitutes value. The assessments also should include early and ongoing dialogue with the patients and reflect comprehensive understanding of the disease management benefits as well as the indirect benefits provided.

While assessments of cost-effectiveness may prove useful in comparing treatments, they have significant limitations, and the lack of available mature data sources preclude the drawing of valid conclusions. Therefore, these assessments should not be used for decision-making that determines access to innovative medicines. As a company focused on improving the lives of patients worldwide, Bristol-Myers Squibb actively encourages the healthcare community to join us in advocating for keeping treatment decisions where they ultimately and rightfully belong―between a patient and his or her healthcare team.

INDICATION

EMPLICITI™ (elotuzumab) is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies.

IMPORTANT SAFETY INFORMATION

Infusion Reactions

• EMPLICITI can cause infusion reactions. Common symptoms include fever, chills, and hypertension. Bradycardia and hypotension also developed during infusions. In the trial, 5% of patients required interruption of the administration of EMPLICITI for a median of 25 minutes due to infusion reactions, and 1% of patients discontinued due to infusion reactions. Of the patients who experienced an infusion reaction, 70% (23/33) had them during the first dose. If a Grade 2 or higher infusion reaction occurs, interrupt the EMPLICITI infusion and institute appropriate medical and supportive measures. If the infusion reaction recurs, stop the EMPLICITI infusion and do not restart it on that day. Severe infusion reactions may require permanent discontinuation of EMPLICITI therapy and emergency treatment.
• Premedicate with dexamethasone, H1 Blocker, H2 Blocker, and acetaminophen prior to infusing with EMPLICITI.

Infections

• In a clinical trial of patients with multiple myeloma (N=635), infections were reported in 81.4% of patients in the EMPLICITI with lenalidomide/dexamethasone arm (ERd) and 74.4% in the lenalidomide/dexamethasone arm (Rd). Grade 3-4 infections were 28% (ERd) and 24.3% (Rd). Opportunistic infections were reported in 22% (ERd) and 12.9% (Rd). Fungal infections were 9.7% (ERd) and 5.4% (Rd). Herpes zoster was 13.5% (ERd) and 6.9% (Rd). Discontinuations due to infections were 3.5% (ERd) and 4.1% (Rd). Fatal infections were 2.5% (ERd) and 2.2% (Rd). Monitor patients for development of infections and treat promptly.

Second Primary Malignancies

• In a clinical trial of patients with multiple myeloma (N=635), invasive second primary malignancies (SPM) were 9.1% (ERd) and 5.7% (Rd). The rate of hematologic malignancies were the same between ERd and Rd treatment arms (1.6%). Solid tumors were reported in 3.5% (ERd) and 2.2% (Rd). Skin cancer was reported in 4.4% (ERd) and 2.8% (Rd). Monitor patients for the development of SPMs.

Hepatotoxicity

• Elevations in liver enzymes (AST/ALT greater than 3 times the upper limit, total bilirubin greater than 2 times the upper limit, and alkaline phosphatase less than 2 times the upper limit) consistent with hepatotoxicity were 2.5% (ERd) and 0.6% (Rd). Two patients experiencing hepatotoxicity discontinued treatment; however, 6 out of 8 patients had resolution and continued treatment. Monitor liver enzymes periodically. Stop EMPLICITI upon Grade 3 or higher elevation of liver enzymes. After return to baseline values, continuation of treatment may be considered.

Interference with Determination of Complete Response

• EMPLICITI is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein.

Pregnancy/Females and Males of Reproductive Potential

• There are no studies with EMPLICITI with pregnant women to inform any drug associated risks.
• There is a risk of fetal harm, including severe life-threatening human birth defects associated with lenalidomide and it is contraindicated for use in pregnancy. Refer to the lenalidomide full prescribing information for requirements regarding contraception and the prohibitions against blood and/or sperm donation due to presence and transmission in blood and/or semen and for additional information.

Adverse Reactions

• Infusion reactions were reported in approximately 10% of patients treated with EMPLICITI with lenalidomide and dexamethasone. All reports of infusion reaction were Grade 3 or lower. Grade 3 infusion reactions occurred in 1% of patients.
• Serious adverse reactions were 65.4% (ERd) and 56.5% (Rd). The most frequent serious adverse reactions in the ERd arm compared to the Rd arm were: pneumonia (15.4%, 11%), pyrexia (6.9%, 4.7%), respiratory tract infection (3.1%, 1.3%), anemia (2.8%, 1.9%), pulmonary embolism (3.1%, 2.5%), and acute renal failure (2.5%, 1.9%).
• The most common adverse reactions in ERd and Rd, respectively (>20%) were fatigue (61.6%, 51.7%), diarrhea (46.9%, 36.0%), pyrexia (37.4%, 24.6%), constipation (35.5%, 27.1%), cough (34.3%, 18.9%), peripheral neuropathy (26.7%, 20.8%), nasopharyngitis (24.5%, 19.2%), upper respiratory tract infection (22.6%, 17.4%), decreased appetite (20.8%, 12.6%), and pneumonia (20.1%, 14.2%).

Please see the full Prescribing Information for Empliciti.

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Endnotes

Empliciti is a trademark of Bristol-Myers Squibb Company.

Revlimid is a registered trademark of Celgene Corporation. All other trademarks are property of their respective owners.