The level of concern surrounding the budget impact of acute myeloid leukemia (AML) has traditionally been low due to the relatively small size of the population in comparison to solid tumors, the high severity of the disease, and a lack of branded treatment options. As a result, few access controls are utilized for AML therapies.
However, with several AML medications recently gaining approval, and many more in the late-stage pipeline, many interviewed payers express concern about the potentially growing budget impact of the indication in the future.
A considerable proportion of the recently approved and pipeline AML treatments are mutationally targeted, and despite their smaller target patient populations, are anticipated to contribute heavily to the increasing cost of therapy. Payers and key opinion leaders also highlight the likelihood of treatment with combinations of targeted therapies in the future, further increasing the level of payer concern. Due to the rising expenditure, payer acceptance will become more critical for the commercial success of new AML therapies.
This analysis examines payer views on recently approved and pipeline AML agents, the tools used to moderate budget impact, and changing evidentiary requirements.
Key Topics Covered:
REGULATORY LABELS AML products in the US, Japan, and five major EU markets Bibliography
PAYER ARCHETYPES Insights and strategic recommendations The budget impact of AML is currently small, but is likely to increase following further approvals Payers currently have a relatively passive approach to AML Moderate levels of restriction are imposed on marketed AML medicines Vidaza and Dacogen AML treatment is becoming increasingly personalized Combinations are likely to be the future of AML Efficacy trumps route of administration in AML due to high unmet need Recently approved and pipeline AML therapies are likely to seek multiple label expansions, resulting in subsequent price decreases Bibliography
ACCESS TO RECENTLY LAUNCHED AND PIPELINE PRODUCTS Rydapt Gilteritinib and quizartinib Vyxeos Guadecitabine and Venclexta Rydapt has the potential to gain positive pricing and reimbursement recommendations, but EU payers might restrict by age Second-generation FLT3 inhibitors could improve clinical outcomes; if not, price will be an important factor Vyxeos likely to be impacted by different funding mechanisms Vyxeos likely to benefit from more favorable infusion schedule Generic Vidaza will set the price benchmark in Europe for certain pipeline therapies Bibliography
CLINICAL TRIAL DESIGN AND EVIDENTIARY REQUIREMENTS Insights and strategic recommendations OS is considered the most important endpoint, but PFS is sometimes sufficient Threshold for OS improvement varies with line of therapy HRQoL data is important, yet rarely collected Age may not be the best predictor of treatment eligibility Investigator choice is accepted but needs to reflect SoC in each market Improvements in complete remission rate are important as they indicate an increased eligibility for stem cell transplants Bibliography
US REIMBURSEMENT Insights and strategic recommendations There are minimal controls for AML therapies Uptake will largely be dictated by specialist physicians New oral AML therapies found in tier 3 of most commercial formularies Prior authorization generally follows FDA labels for recently approved AML therapies Bibliography
JAPAN Price premiums are awarded for added benefit or innovation Pricing of launched AML treatments Bibliography
PRICING IN THE FIVE MAJOR EU MARKETS
FRANCE Insights and strategic recommendations ASMR rating has an impact on pricing Dacogen is not included on the liste-en-sus and is unlikely to be routinely reimbursed in the hospital setting Vidaza reimbursed only for those with 20-30% blasts Exclusion from the liste-en-sus will likely be a cost-containment measure for new hospital-administered drugs Oral AML therapies will be fully reimbursed irrespective of ASMR rating Relapsed and refractory AML patients are considered to have the highest unmet need Mutationally targeted therapies may be able to achieve higher prices in negotiations with the CEPS Vyxeos could gain an ASMR III in France, and be used alongside chemotherapy add-ons that are expected to gain approval Bibliography
GERMANY Insights and strategic recommendations Positive assessment from the G-BA will impact price negotiations Recently approved and pipeline orphan therapies will be given an automatic additional benefit rating from the G-BA Without mature Phase III data, orphan drugs are likely to receive no additional benefit at the second G-BA assessment Dacogen received a minor additional benefit rating due to unclear OS data Price negotiations after the benefit assessment are the main levers for sickness funds to control expenditure on AML drugs Cost-containment tools for AML may be implemented as the market gets more crowded Label expansions to wider patient populations will result in multiple G-BA assessments and pricing negotiations Unmet need is not considered in an added benefit assessment by the G-BA Mutationally targeted therapies will not be viewed more favorably by the G-BA, and reimbursement of genetic tests may be an issue Expensive AML medications will require an NUB to gain funding through the hospital system Vyxeos is unlikely to be assessed by the G-BA, and access will depend heavily on price Safety issues are likely to limit IDHIFA's uptake in the German market Bibliography
ITALY Insights and strategic recommendations All marketed AML treatments are reimbursed in Italy AML drugs assessed and reimbursed by AIFA are found in regional formularies investigated Some Italian regions impose further restrictions Gaining a therapeutic innovation rating will be highly beneficial for new AML medications Rydapt has the potential to receive innovative or conditionally innovative drug status Bibliography
SPAIN Insights and strategic recommendations National reimbursement decision is not a major access barrier in Spain Regional and local bodies give more stringent reimbursement recommendations Restrictions from local authorities often have the greatest impact Dacogen received a broad recommendation in its IPT Recommendations for Dacogen and Vidaza differ regionally and locally Drugs targeting the relapsed/refractory setting may gain easier access Label expansions will result in price decreases in Spain Mutationally targeted therapies are likely to be assessed more favorably in Spain Early access can be granted in Spain for one year, based on provisional data
List of Figures Vyxeos is expected to be recommended at a national level, but pricing and local recommendations will be the most important Bibliography UK Insights and strategic recommendations NICE and SMC determinations drive reimbursement decisions NICE and SMC recommend Vidaza for patients with 20-30% blasts only Vidaza required PAS for acceptance by NICE and SMC Dacogen is not available on the UK or Scottish healthcare system NICE committee fails to recommend Rydapt for reimbursement Cancer Drugs Fund redesigned for goal of early access to novel drugs Payers are likely to be more reactive rather than proactive Treatment algorithms will likely have an important impact on the uptake of AML therapies in the future Bibliography