Amgen Statement and Response to ICER Revised Value Framework Proposal and Osteoporosis Revised Scoping Document

The Institute of Clinical and Economic Review (ICER) announced in February they will revise the framework for assessing the value of medicines. Amgen’s comments on the proposed revisions recognized that there is no single answer to the question of value, as individual institutions, physicians, payers and patients view value from their unique perspective. Importantly, the patient perspective must remain at the center of any assessment of the value of innovative technology.

There is clearly a need to have a robust and open conversation about value and we urge ICER to assess value with flexibility, based on parameters that are science-based and relevant to patients and other stakeholders. ICER is not a budget-holder or decision-maker, nor is it accountable to either one. Thus, like other individuals and organizations performing value assessments (Center for Evaluation of Value and Risk in Health [CEVR], Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Center for Medical Technology Policy [CMTP], International Society For Pharmacoeconomics and Outcomes Research [ISPOR], academicians),^1-3 ICER should transparently present its assessments in conjunction with peer-review, to advise stakeholders about value by conducting objective and systematic assessments formed with wide stakeholder involvement based on solid clinical evidence. The determination of value should be left to the unique stakeholders making decisions about medical care in clinical practice. The need for methodologically rigorous advice and flexibility rather than a single answer about value has never been more apparent.

Surprisingly, ICER will review innovative medicines not yet on the market. For example, in January, ICER issued a draft scoping document outlining a planned comparison of two not-yet-approved bone-forming agents to the only currently available bone-forming agent, teriparatide. The assessment also proposes to compare bone-forming agents to bisphosphonates, which work by a different mechanism, reducing bone breakdown, have a longer time to clinical effect, and are generally used as longer-term therapy in a broader and lower-risk patient population.⁴

Real world data reflect that bone-forming agents are typically used for patients with more severe osteoporosis and higher fracture risk than those treated with bisphosphonates.⁵ Further, bone-forming therapy is administered over a short time-frame - less than two years - in which rapid bone formation is observed and desired.⁶ Bisphosphonates are used on a longer-term basis with a more gradual onset of effect, over three to four years as shown in clinical trials.^7-11 An appropriate value assessment of novel bone-forming agents would follow a few basic principles:

1) Compare management strategies for patients at high risk for fracture, specifically those identified as being a high risk in the near-term (in the next one to two years), such as patients who have had a prior fracture, which reflects the current patient demographic in which bone-forming therapy is used.

2) Compare bone-forming agents to one another, since treatment onset for anti-resorptive agents are generally not comparable due to much longer primary endpoint assessment in clinical trials (three to four years) versus one to one and half years for bone-forming agents. In addition, the latter is generally used in lower-risk patients on a long-term basis, unlike the short-term use of bone-forming therapy in higher-risk patients.

3) Employ valid methods of evidence synthesis. The trials of osteoporosis therapies are heterogeneous, assessing populations with different risk profiles and with varying durations of follow-up time for efficacy assessment, and thus great care must be given to the methods used to assess comparative efficacy to yield valid results. Methods that haphazardly combine heterogeneous data will result in results that are invalid and misleading.

4) Ensure that analyses undergo expert review, and that relevant stakeholders with expertise in bone disease and osteoporosis are on the any voting panels.

The impact of osteoporotic fractures is significant for patients and society. After a woman has an initial fracture, she is five times more likely to suffer another fracture within a year.¹² Women at high risk of fracture in the near term include women who have already had a fracture, especially women over the age of 65 or who have low bone mineral density.¹³ These women may benefit from bone-forming agents, and data suggests that use of bone-forming therapy prior to anti-resorptive therapy is the optimal sequence, with the potential for transient loss of hip bone mass density when patients transition from anti-resorptive therapy to teriparatide.¹⁴

More than two million bone fractures occur each year in the U.S.^15-19 Roughly one in two women over 50 years of age will have an osteoporotic fracture in their lifetime,^20-22 and fractures are associated with clinical morbidity and a reduction in quality of life.^23-26 We agree with a recent statement from the American Society for Bone and Mineral Research, the National Osteoporosis Foundation and the National Bone Health Alliance on the need to be aware of the risk and anticipate ways to prevent secondary fractures. The annual direct medical cost of osteoporotic fractures in the U.S. will rise from $17 billion in 2005 to $25.3 billion by 2025.¹⁷ Preventing more fractures earlier in treatment for women at high near-term risk has the potential to change this cost trajectory.

If the ICER draft report is not highly shaped by clinical practice and incorporation of real world evidence from these higher-risk patients, it will result in a spurious assessment of the value these agents can bring to patients.  Amgen has developed an economic model of the cost-effectiveness of bone-forming agents (soon to be published).  The model projects that a course of therapy with a novel bone-forming therapy such as investigational EVENITY^™ (romosozumab) can provide good value to patients, payers, the health care system and society compared with appropriate comparators (e.g., teriparatide) in the clinically relevant higher-risk target population.  In addition, 12 months of treatment with EVENITY with transition to an anti-resorptive, such as Prolia^® (denosumab), provides ongoing fracture risk reduction over two additional years of sequenced use.²⁷

As a leader in the bone health field, Amgen remains committed to offering insight and experience to inform how new innovations may benefit the patients who need them most.