Treating rare disorders: time to act on unfair prices

Abstract

The first disease-modifying treatment for spinal muscular atrophy (SMA), nusinersen, was approved by the US Food and Drug Administration (FDA) on Dec 23, 2016, and by the European Medicines Agency (EMA) on May 30, 2017. The approval was based on evidence of clinically meaningful improvements in motor milestones in young children with varying degrees of disease severity from two clinical trials (ENDEAR, NCT02193074, and CHERISH, NCT02292537). The regulatory approval is a historic development, but it is unlikely that the drug will be available to all patients who would benefit from treatment, unless its manufacturer offers a fairer price than the current cost of this drug. Nusinersen, an antisense oligonucleotide, is given by intrathecal injection, at a cost of US$125 000 per injection. Six doses are required in the first year and three doses per year after that; hence, the treatment amounts to US$750 000 for the first year and US$375 000 for every year afterwards. This estimate does not account for administration costs. The marketing process has just started in Europe, separately for each country, with prices likely to vary between countries. Although the drug has not been approved in all countries yet, nusinersen is available worldwide, depending on local laws and regulations, through the manufacturer's Expanded Access Programme (EAP). However, even though the drug has been approved for all SMA types, only patients with infantile-onset SMA (consistent with type 1) are eligible for the EAP. Similarly, not all US-based health insurance companies will cover nusinersen therapy for patients with late-onset SMA (consistent with type 2 and 3) as the benefits in clinical trials were less clear compared with those in patients with type 1 SMA. With the high unmet medical needs in patients with SMA and the absence of an alternative drug, broad and sustainable access to nusinersen is essential. However, the high cost of the drug will limit patients' access to it. Determining who will pay for, and thus who will have access to, nusinersen can be a long, complex administrative process, sometimes involving judicial procedures. The high price for nusinersen is in line with the price of drugs for other rare disorders (eg, cerliponase alfa for Batten disease costs US$702 000 per year; eteplirsen for Duchenne muscular dystrophy has a price of US$300 000 per year for a 25 Kg patient, up to US$750 000 for an older, heavier patient) and access to these drugs is restricted similarly to that of nusinersen. These and other high-priced drugs threaten health-care systems and insurance companies as drugs for rare diseases are likely to be needed indefinitely (eg, a 5-year nusinersen treatment will cost about US$2.25 million per patient) rather than temporarily, as with certain cancer drugs. The development of a drug is expensive, regardless of whether the drug is intended to treat a rare or common disease. However, with many new disease-modifying drugs for rare disorders in the pipeline, a debate about fair prices is overdue. In March, 2017, the American Academy of Neurology (AAN) released a position statement on drug prescription prices stressing that “action must be taken to ensure that prescription medications are accessible for patients with complex, chronic neurologic conditions”. The AAN calls for price negotiations, transparency in drug pricing, and reimportation of high-quality drugs from Canada when these are cheaper than in the USA. Development of treatments for rare diseases is still a major public health goal as most rare diseases are still without any effective treatment (of more than 6000 rare diseases, treatment is only available for around 200 of them). On Aug 9, 2017, the International Rare Diseases Research Consortium (IRDiRC) published its vision for 2017-2027: “Enable all people living with a rare disease to receive an accurate diagnosis, care, and available therapy within one year of coming to medical attention”. To accomplish this ambitious vision, three goals have been set: having a diagnosis within one year if the disorder is known; developing 1000 new therapies, particularly for diseases with no approved treatment; and creating methods for assessing the impact of diagnoses and therapies for patients with rare diseases. In SMA, long-term evidence of cost-effectiveness is needed, but those studies will not be completed for a few years. The current high prices for rare disease drugs will be impossible to bear by any health-care system. A global and cohesive strategy is needed. Affordable health care should be the priority of all stakeholders—including health insurers, pharmaceutical companies, and policymakers.