UPFRONT

The Genetic Lottery

Peter K. Kaiser, MD

At the recent Retina Society meeting in Paris, Spark Therapeutics reported its positive phase 3 results using its ground-breaking, gene-therapy product, SPK-RPE65, for the treatment of autosomal-recessive RPE65-related inherited retinal degenerations.

Due to its orphan drug and breakthrough therapy designations, a small trial of 31 patients achieved the primary outcome of a statistically significant improvement in full-field light sensitivity threshold testing and mobility course navigation, although a significant improvement in vision was not seen. The company plans to file for a Biologics License Application next year.

Importantly, no safety signals were seen in the study — specifically no deleterious immune responses. Given the history of gene therapy safety, this fact is almost as important as the efficacy findings. Some of the patients in the phase 1 study are approaching five years after their only treatment and are still experiencing improvements in visual function. This is a monumental finding for such devastating genetic diseases as Leber congenital amaurosis (LCA) type 2 and some forms of retinitis pigmentosa.

With this result, we are entering a very exciting time in our field. Where we had no hope and often watched helplessly the inexorable decline in vision, we now can fight back.

The big question with gene therapy is how much will it cost. Alipogene tiparvovec (Glybera, UniQure, Amsterdam, the Netherlands) a gene therapy drug approved in Europe for the treatment of familial lipoprotein lipase deficiency, costs €44,000 per vial. With the average patient needing 42 injections from 21 vials, the cost more than $1.2 million.

The treatment does not cure the ultrarare disease of the pancreas for which it is approved, but reduces pancreatitis by 50%. Wall Street and Big Pharma have certainly taken notice, with small gene therapy companies being valued at billions of dollars without a commercial product.

What about the other side of the equation? In countries with single-payer healthcare systems, such therapies that provide lifelong benefit are easier to have their incredible costs justified. However, in a private-payer system like the US, where patients may switch insurance companies annually, a single upfront cost is hard to swallow. Will an annuity-type payment system work?

If the treatments decrease insurance costs over time, eg, due to fewer hospitalizations for severe pancreatitis, then insurance companies may be more amenable to covering the cost. The number of patients with the disease will certainly be a factor. Only approximately 200 or so patients would need Glybera. So all gene therapy products will not be considered equal by the insurance industry.

In the case of LCA, there is no long-term benefit for the insurance carrier, but there is a massive benefit for the patient and his or her quality of life. How much is that worth?

As they say in the MasterCard commercials — priceless.