Amgen's Response to ICER's Draft Report ‘Treatment Options for Relapsed or Refractory Multiple Myeloma: Effectiveness and Value’

Apr. 8, 2016

People suffering from multiple myeloma usually receive several lines of therapy given the progressive and incurable nature of the disease. Treatment choices are highly individualized based upon treatment goals, and factor in therapies used in prior lines, responses and toxicities associated with those therapies and other factors including age, co-morbidities and transplant eligibility. Analyses that attempt to define the value of regimens in specific lines of therapy without considering these factors may not be clinically relevant.

When it comes to relapsed or refractory multiple myeloma, and the impact Kyprolis® (carfilzomib) has on patients with the disease, the Kyprolis Global Economic Model (K-GEM)i provides a framework for considering value. The K-GEM was co-developed with input from experts worldwide over a number of years, and has been used as the basis for a number of statutory Health Technology Assessment analyses globally. Unlike the ICER model, which relies on an indirect treatment comparison across multiple trials that does not address trial heterogeneity, the K-GEM provides a robust framework for evaluating value based on head-to-head trial data. The K-GEM incorporated data directly from the head-to-head Phase 3 trial (ASPIRE) in patients with relapsed or refractory multiple myeloma who had received one to three prior therapies. The ASPIRE superiority trial showed that the addition of Kyprolis to lenalidomide and dexamethasone (KRd) resulted in superior improvement (additional 8.6 months) in median progression-free survival (PFS) compared to lenalidomide plus dexamethasone (Rd) (26.3 months vs. 17.6 months, hazard ratio for progression or death= 0.69; 95 percent confidence interval [CI]: 0.57 to 0.83; p<0.0001).

Tables 13 and 14 in the ICER draft reportii estimated total life-years for KRd and Rd in patients who had received one prior therapy to be 4.70 and 3.53, respectively, and in patients who had received ≥2 priors was 4.37 for KRd and 3.25 for Rd. In comparison, the K-GEM, based on head-to-head data, estimated total life-years achieved with KRd and Rd as 7.83 and 5.84, respectively, in patients who have received one to three prior therapies, over a life-time horizon with a survival gain of 23.88 months. The estimated total survival for Rd based on the K-GEM model is similar to that estimated in a life-time cost-effectiveness model from the UK National Health Service perspective, which showed that Rd achieved a total of 5.37 life-years.iii

ICER’s indirect method means their results on KRd efficacy and life-years differ from the K-GEM. Tables 13 and 14 in the ICER draft report show estimates of the incremental cost per quality-adjusted life-years (QALYs) gained for KRd vs Rd as $267,464 and $312,840, respectively. The K-GEM pre-progression cost estimates for the multi-year KRd regimen are $356,041 with 30.8 percent ($109,779) of the pre-progression costs being attributable to Kyprolis and the remainder, 69.2 percent ($246,262) being attributable to Rd and other concomitant medications. The K-GEM derived QALYs were 5.88 for KRd and 4.21 for Rd. The analysis from K-GEM showed that the incremental cost per QALY gained for KRd versus Rd is $107, 520, and the incremental cost per life-year gained is $89,957.

The economic value of Kyprolis is estimated to be well below the benchmarks of $150,000-$300,000 per QALY cited as reasonable benchmarks for cancer in the U.S.iv A critical assumption in economic models of cancer, where trial results have not yet matured enough to produce the full extent of survival, is the extrapolation of overall survival. This is a common evidence-based practice in health economics, but should in no way be construed as a claim of extended survival.

Amgen believes that value assessments are one input that can inform the complex decisions around relative value and payer formulary management. We agree with Steve Ubl, president and CEO of Pharmaceutical Research and Manufacturers of America, and Dan Leonard, president of the National Pharmaceutical Council, in their March 31st blog for the Hill, ‘Ensuring that value frameworks are sound before using them in public policy or as the basis for decision-making is essential – value assessments that are not developed transparently, based on rigorous methods or are vulnerable to misinterpretation and misuse have the potential to hinder a patient-centric health care system and progress against unmet medical needs’.v

The ICER draft report specifically states that they do not consider social value. We agree with Tom Philipson’s April 5th opinion piece in Forbes, ‘Few would disagree that rewarding the full social value of a drug is a good idea, but the failure of current frameworks to accurately and transparently assess value poses a threat to the future pipeline of new drugs. Put simply, our current measures of value are not only too narrow but are shortsighted. Pricing and coverage decisions made on the basis of incomplete value frameworks run the risk of reducing future innovation by penalizing drugs that actually offer value to society’.vi


i. Amgen data on file.

ii. Treatment Options for Relapsed or Refractory Multiple Myeloma: Effectiveness and Value, April 7, 2016:

iii. Schey S. Abstracts of the American Society of Hematology 53rd Annual Meeting, December 10-13, 2011, San Diego, California, USA. Blood. 2011;118(21):3-1820

iv. Neumann PJ, Cohen JT, Weinstein MC. Updating Cost-Effectiveness — The Curious Resilience of the $50,000-per-QALY Threshold. N Engl J Med 2014; 371:796-797)

v. Principles to support patient-centered value assessment,  The Hill, March 31, 2016.

vi. Value In Healthcare -- Time To Stop Scratching The Surface,