Gene therapy and fair value.

Retinal pigment epithelial cells in
RPE65-mediated retinal disease

Back in March, I wrote a piece regarding the coming impact of high ticket gene therapies on healthcare budgets. December saw the FDA approval of Spark Therapeutic's Luxturna™ (voretigene neparvovec), a unique treatment for biallelic RPE65-mediated inherited retinal disease, a form of Leber's congenital amaurosis, which results in early onset, progressive loss of vision.

Predictably, Luxturna's approval has reopened the debate around the cost of leading edge therapies. At around $850,000 to treat both eyes, Luxturna™ pricing is somewhat lower than the $1 million plus price tag anticipated by industry analysts, although it's still the most expensive drug in the US by list price.

Justifiable? Perhaps. Gene therapy product approval is not a guaranteed path to riches. As with other genetic disorders, the potential treatment population is small, being around 1000-2000 sufferers in the US, with around the same number in Europe. Moreover, Luxturna™ is a one-time treatment. While even modest uptake should cover Spark's development costs, the overall return to Spark will be, by pharma standards, unremarkable.

Spark appears pragmatic in its approach to reimbursement, offering insurers rebates should patients fail to achieve an agreed degree of benefit, although with only limited and short-term study data available, defining a improvement for rebate purposes will not be easy. Spark is also thought to be considering an annuity model, allowing insurers to pay over time [see update of 12th January below]. 

So much for cost, but what about value? Although not an easy calculation, tallying the lifetime benefit accruing from reduced direct and indirect medical costs, increased individual economic activity and quality of life improvement, might come close to justifying Luxturna’s price tag.

A draft assessment published by the Institute for Clinical and Economic Review published just prior to Luxturna's approval concluded that, although likely to result in better outcomes than standard care, Luxturna would probably not prove to be cost-effective at an assumed acquisition cost of $1 million.  Another crank of the spreadsheet incorporating the actual drug price and post-approval efficacy data, particularly the durability of benefit, could tip the balance in Luxturna's favour.

The UK's National Institute for Health and Care Excellence (NICE) recently concluded that, compared with the cost and risk associated with stem cell transplantation for the treatment of adenosine deaminase deficiency–severe combined immunodeficiency (ADA-SCID or "bubble boy" syndrome) GSK's gene therapy, Strimvelis™, provided both the best treatment option and value for money, despite its  €594,000 (around £505,000) price tag.

Although invariably flawed, cost-effectiveness analysis needs to be at the centre of gene therapy pricing and adoption debates. Such analyses may not always prove favorable, but without an objective means of establishing fair pricing and reimbursement, gene therapies could become out of reach for many patients. The commercial abandonment of Glybera™,a gene therapy for lipoprotein lipase deficiency and announcement of GSK's intention to abandon Strimvelis® (and rare disease therapy development in general) are portents that should not be ignored.

Photo credit: National Eye Institute, National Institutes of Health.

For most cancer drugs, the price isn’t right

Drug pricing is now a regular headline feature. The past year saw Valeant, Mylan, Pfizer and United Health receive unwanted attention around seemingly unjustifiable increases in the prices of patent-expired medicines and a promise from the Trump presidency that the soaring cost of medicines would be brought under control.  

Spiralling prices impact on all medical conditions, but  the fair pricing of cancer drugs is particularly emotive. The six-figure cost of newer therapies is straining public and private healthcare systems. Stiff co-payments impose an often intolerable burden on US cancer patients and their families and high pricing restricts access to cancer drugs in less-developed economies.

Cancer drug development is expensive. Newer treatments target particular mutations or other aberrations specific to certain tumour types, with the consequence that the accessible patient population is reduced to a subset of cancer sufferers.

Developers argue, reasonably enough, that pricing must cover the expanding cost of development and still generate sufficient profit for reinvestment in R&D. The costliest of cancer drugs can still represent good value if treatment outcomes, such as increased survival or measurable improvement in quality of life over best standard of care can be expected for the majority of treated patients, but a large and growing body of evidence points to a serious disconnect between cancer drug pricing, clinical efficacy and true value.

 

An analysis published this month by Vivot and colleagues compared the clinical efficacy of cancer treatments approved by the FDA between 2000 and 2015 using measures of clinical benefit developed by American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO).

Evaluation was possible for 37 of the 51 drugs approved by the FDA. ESMO criteria indicated that just over one-third of drugs (13 or 35%) showed “meaningful clinical benefit”. The scale of benefit obtained by applying ASCO criteria was in the range 3.4 to 67, with a median value of 37. No relationship was indicated between benefit and price.

A similar study by Salas-Vega and colleagues at the London School of Economics found that cancer drugs approved in the decade to 2013 resulted in no discernible increase in overall survival for certain cancers (breast cancer being a notable exception), with all new drugs contributing an average gain in overall survival benefit of just under three and a half months.

Blaming the situation on drug company rapaciousness is naive, although it’s clearly in the industry’s interest to be viewed by both governments and the public as part of the solution. Alignment of pricing and outcome needs a major shift in the basis for drug approval (one that may not be compatible with President Trump’s vision of a truncated FDA approval process), along with a better understanding on the part of prescribers, payers and patients of cancer drug benefit in the context of toxicity, quality of life and individual and societal cost.

Future cancer treatments may perhaps be truly transforming, with functional cure becoming a realistic expectation. Science aside, the challenge will be in developing equitable payment mechanisms that reward innovation without placing cancer treatments out of reach of the majority.

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Clinical Benefit, Price and Approval Characteristics of FDA-approved New Drugs for Treating Advanced Solid Cancer, 2000-2015. A Vivot et al. Ann Oncol mdx053. https://doi.org/10.1093/annonc/mdx053. http://tinyurl.com/j4uhv3f

Assessment of Overall Survival, Quality of Life, and Safety Benefits Associated With New Cancer Medicines. Sebastian Salas-Vega, Othon Iliopoulos and Elias Mossialos. JAMA Oncol. Published online December 29, 2016. doi:10.1001/jamaoncol.2016.4166. http://tinyurl.com/glo9gvz