The healthcare provider of the commercial health insurance companies „GWQ ServicePlus“ and the Association of Private Health Insurers (PKV) have each agreed to separate performance-related early access compensation agreements for Zolgensma® (April 16-23, 2020), but details of the performance aspects of the contracts were not disclosed. Find out why the cost and management of these treatments are well suited to managed entry agreements – and which EMA approach may be the most commercially viable for manufacturers. IndicationZolgensma (onasemnogene abeparvovec-xioi) is a gene therapy based on adeno-associated viral vectors indicated for the treatment of paediatric patients under 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the motor neuron survival 1 (SMN1) gene. To cover the new therapy, Novartis offers payers outcome-based agreements that only spread the total cost over five years if the drug continues to act. Payers welcomed the new models. As of July 2019, about 40 percent of commercial life and four Medicaid plans had policies. Coverage rates quickly increased to 90 percent of working life and 30 percent of Medicaid patients in October, according to CEO Vas Narasimhan. In addition, almost all patients on the label received final approvals after Novartis followed certain appeal procedures, he said. The new Gene Therapy Zolgensma® recently received the highest reimbursement price ever recorded in Japan and the conditional approval of the EMA paves the way for its launch in the European market, with performance-based early access contracts concluded in Germany and a joint evaluation of the ETS planned in Belgium, Ireland and the Netherlands. Using a matrix like the one shown in Table 2 below, we can begin to assess the sustainability of the gene therapy pipeline and examine the extent to which MEAs can support a gradual budget impact instead of huge upfront costs in advance.
As Zolgensma has shown, SMA Type I is clearly well suited for multiple managed entry options, including annuity-based payments (which translates into a price similar to competitors` per year) and outcome-based agreements (based on standardized criteria, measurable + validated outcomes). It is clear that different pathological areas require different approaches to EMAs. The cost savings resulting from the reduction/independence of factor VIII in hemophilia A are likely to result in a relatively simple outcome-based agreement, motivated by the reduction in the use of factor VIII replacement. For DMD, the price of comparators and the use of muscle dystrophin in previous studies could support either an annuity-based agreement or an outcome-based agreement determined by muscle dystrophin levels. Novartis gets U.S. approval – and payers` blessing – for the $2 million Zolgensma gene therapy. PMLive www.pmlive.com/pharma_news/novartis_secures_us_approval_ _and_payers_blessing_for_$2m_gene_therapy_zolgensma_1289221 (2019). A recent white paper published by CVS Health paints a bleak picture; By calculating the impact on total five-year costs of a selection of short-term assets in the gene therapy pipeline, the authors calculated a small market effect of $14.85 billion and a high market effect of $45 billion in the United States alone. Worryingly, this was only due to the 11 projects closest to the market.1 If the market impact of clinically successful gene therapies comes close to these numbers, it is highly unlikely that healthcare systems will be able to cope with them. Oklahoma, Colorado and Michigan also have federal approval for value-based Medicaid deals. Louisiana and Washington are testing a different strategy by using subscriptions or fixed payments for hepatitis C drugs.
„We are at the forefront of an exciting time in healthcare where we will be able to see great advances in medical care with potentially curative gene therapies. While there are many issues that we need to consider as a healthcare system, nothing changes in our work to ensure that these life-saving drugs are affordable and available to patients who need them,“ said Steve Miller, MD, Clinical Director, Cigna Corporation. We look forward to continuing the work we have begun with AveXis to find unique solutions such as installments and outcome-based agreements for these life-changing gene therapies. Novartis offers a „Day One“ access system for European countries3 with the goal of promoting rapid access and leveraging a combination of multi-tiered annual payments, outcome guarantees and services to support patients and treatment centers. Under this system, the original list price is refunded, but most importantly, Novartis guarantees discounts in line with the country-specific reimbursed prices that are negotiated later in the HTA process. Government payments, reviews and reimbursements if the drug is not effective would extend over five years. Novartis regularly offers a five-year payment plan for Zolgensma. The company said in a statement that these so-called value-based or earnings-based agreements are also becoming routine.
He is said to be in „active discussions“ with Massachusetts. In summary, it can be said that the high cost and uniqueness of gene therapies seem particularly well suited to MEAs. It will be important for manufacturers to consider early in development how an MEA can support commercialization, how payers perceive the multiple potential approaches of the EMA, and what outcomes and measures should form the basis of this agreement. Analysis of a number of factors that contribute to the sustainability of disease domains focused on gene therapy shows significant variability in these diseases. Some disease areas, such as hemophilia A and DMD, appear to be particularly well suited to relatively simple MEAs focused on cost compensation. For diseases with poorly established natural history, such as the previously studied gm1 gangliosidosis example, manufacturers may be pushed towards more established outcomes such as survival rather than biomarker/natural history based outcomes. Other areas of the disease are likely to require more innovative thinking. For diseases with a poorly established natural history, such as GM1 gangliosidosis, a results-based agreement may be based on a well-established outcome such as survival. For Parkinson`s disease and wet AMD, the prevalence and lack of clear cost compensation could lead payers to prefer a long-term, results-based agreement that ensures health system affordability. This is another important consideration when planning an MEA; What is the „expiration date“, the date by which any data uncertainty should have been resolved? Is your MEA a simple five-year pension plan? At what point will the production of evidence from pivotal studies/real-world evidence (RWE) be mature enough to convince payers of good value for money? This continues the recent trend of German payers entering into outcome-based deals for expensive disposable therapies – GWQ entered into a similar initial agreement for Kymriah® where reimbursement depended on survival outcomes. German payers have always been reluctant to this type of venture, but have shown a willingness to consider it when CAR-T cell therapies arrive.
„Innovative science like Zolgensma has forced us to be just as innovative when it comes to providing tailored access solutions to meet the many needs of payers and patients,“ said Dave Lennon, President of AveXis. „We are working together to accelerate hedging decisions with government and commercial payers. We offer a pay-for-time model for this unique treatment to accommodate the current structure of the U.S. healthcare system, and we have also entered into outcome-based agreements with payers because we believe in the long-term value of Zolgensma and are ready to support therapy. „It should be noted that a treatment can be subject to several MEA approaches, for example, an annuity-based and results-oriented contractual system, as proposed in Germany for Zynteglo. Zynteglo, an ex vivo gene therapy for transfusion-dependent thalassemia β (TDT), is a good example of a results-based agreement. bluebird bio has been praised in some quarters for its innovative approach to MOEs, so that 80% of Zynteglo`s list price of 1.575 million euros was on the table with its first deal in Germany, with an additional payment based on the independence of transfusion. MEAs are increasingly seen as an important solution to address the unique challenge posed by individual treatments such as gene therapies. Table 1 below describes the range of MEAs available to manufacturers and payers, each with examples. .