Preparing to pay for a new era of effective gene therapy

Could you imagine seeing stars in the night sky for the first time or even the site of your own parents’ faces after ten or even twenty years of significant visual impairment? The Food and Drug Advisory Committee heard personal testaments like these from patients explaining their miraculous results as part of two experimental gene therapy trials.

More than 25 years in the making, the FDA approved Luxturna® (voretigene neparvovec-rzyl), the first gene therapy for an inherited disorder involving a progressive form of blindness, typically starting in early childhood. Currently, no pharmaceutical alternative is available for these patients.

Spark Therapeutics has set an initial treatment price tag of $850,000 ($425,000 per eye intervention). The company also announced the possibility of outcomes-based rebates – a common practice in Canada and some European countries, but not currently used in the U.S. Spark is also floating the prospect of payments spread out over the course of several years, as opposed to one lump sum. Of course, this model has major implications for employers with stop loss insurance.

My colleagues and I have been following this ground-breaking therapy for months, as it may be a bellwhether treatment model and pricing approach for future gene therapies, which have faced several challenges to-date. Those obstacles include gene delivery and activation, immune response and avoiding unintended consequences like cancer. Thankfully, Luxturna® has no reported cases of cancer yet; however, long term data is necessary since the longest reported efficacy outcome is four years from a single case.

As with all gene therapies, genetic testing is required to predict for a positive therapy outcome with Luxturna®. And due to the complexity of preparation and administration, it will only be available at eight designated treatment centers, known as “Ocular Gene Therapy Centers,” dispersed throughout the country. Further technical details may be found below or within the product information.

The stakes are high and we have already seen a variety of health plan and PBM responses to the product’s approval. This drug targets a gene mutation that causes damaged cells in only about 1,000 – 2,000 patients within the United States. However, other therapies will likely follow this model, and with wider applications as the science evolves.

Employers need to be ready. What drugs will our plans pay for? What criteria will apply to make sure the high costs are producing big, positive results? How will the “supply chain” need to be controlled to optimize outcomes and minimize profiteering?

As a mother and pharmacist, I am cautiously optimistic as we look to the future. Long term efficacy and safety information, as well as novel payor model implications, will be on the forefront. Luxturna® is one to watch!

– Kelly Prymicz, PharmD, RPh

Kelly Prymicz, PharmD, RPh, is a consultant with the Chelko Consulting Group where she helps employer-sponsored health plans better understand and manage quality of care and waste issues associated with the prescription drug spend in their medical TPA and PBM administered benefits.

Technical Notes: Luxturna® (voretigene neparvovec-rzyl)

Luxturna® targets the RPE65-mutation that causes damaged cells within the retina. Therefore, genetic testing to confirm biallelic RPE65-mutation is necessary for a positive therapy outcome.This RPE65-mutation affects 1,000 – 2,000 patients within the United States. RPE65-mutation associated Leber Congenital Amaurosis (LCA) estimates approximately four new cases per year. Due to the low incidence and expected one-time treatment, Luxturna® received FDA granted application of Priority Review, Breakthrough Therapy designation, Orphan Drug designation, and Rare Pediatric Disease Review Voucher. Currently, no pharmaceutical alternative is available for these patients.

Forty-one patients, eighty-one eyes in total, were enrolled in two different trials ranging in age from 4 to 44. Patients 45 years of age and older were not studied and viable retinal cell confirmation by a physician is critical for therapy success.  Patients less than 12 months of age are not eligible for therapy due to high cell proliferation rates which may lead to a lack of efficacy. Each eye must have separate procedure days within a close interval, but no fewer than 6 days apart. Patients should adhere to the provider’s medication order for oral corticosteroids, such as prednisone, to reduce the risk of an immune response which will start three days prior to the procedure and gradually decrease during the following ten days.

Gene therapy has faced several challenges including gene delivery and activation, immune response, and avoiding negative unintentional consequences like cancer. Luxturna® has overcome previous challenges by delivering a copy of a normal gene encoded RPE65 to cells in the retina. However, long term data is necessary since the longest efficacy data is four years from a single case. Reported adverse events of greater than or equal to 5% thus far include conjunctival hyperemia (22%), cataract (20%), increased intraocular pressure (15%), retinal tear (10%), dellen (thinning of the corneal stroma) (7%), macular hole (7%), subretinal deposits (7%), eye inflammation (5%), eye irritation (5%), eye pain (5%), and maculopathy (wrinkling on the surface of the macula) (5%)

Gene therapy is paving the way for innovation and not an issue expected to go unnoticed. The FDA press release from December 19, 2017 states, “The culmination of decades of research has resulted in three gene therapy approvals this year for patients with serious and rare diseases. I believe gene therapy will become a mainstay in treating, and maybe curing, many of our most devastating and intractable illnesses,” said FDA Commissioner Scott Gottlieb, M.D. “We’re at a turning point when it comes to this novel form of therapy and at the FDA, we’re focused on establishing the right policy framework to capitalize on this scientific opening. Next year, we’ll begin issuing a suite of disease-specific guidance documents on the development of specific gene therapy products to lay out modern and more efficient parameters — including new clinical measures — for the evaluation and review of gene therapy for different high-priority diseases where the platform is being targeted.”