Why Regenxbio’s eye gene therapy would have to be the cheapest yet

If investors have visions of Luxturna-like prices they might need to blink and look again.


Regenxbio is moving swiftly into phase II with RGX-314, its gene therapy for wet age-related macular degeneration, after promising phase I data showing that the project could stimulate production of a monoclonal antibody fragment to VEGF.

But if investors in the Maryland-based group believe that it can charge the $700,000 a patient that Spark does for its gene therapy they might need to think again. Regardless of the convenience of a theoretically once-and-done treatment, Regenxbio needs to be mindful of the fact that its therapy would be going up against cheaper biologicals. “I would advise Regenxbio to price it as reasonably as they possibly can,” Professor Peter Campochiaro, a top ophthalmologist who was lead investigator in RGX-314’s trial, told Vantage. “There’s no question that this is a price sensitive market.”

Furthermore, developers of these older drugs are trying to optimise them to require fewer injections.This has not always gone smoothly, as shown today by the FDA's rejection of Regeneron's application for Eylea dosed every 12 weeks – but could still pose a problem to Regenxbio's business model.

The case for gene therapy

There is a case to be made for gene therapy in wet AMD. While Lucentis, Eylea and off-label Avastin showed in clinical trials that they can maintain or improve visual acuity on average over up to two years, in real-world practice they have not been as effective.

Professor Campochiaro, who researches the disease at Johns Hopkins University, points to the Aura study of patients prescribed Lucentis, which found that on average patients got five injections in the first year and 2.2 in the second , as opposed to the monthly jabs required on the label. At a minimum, the number of doses a patient should get is seven in the first year and four in the second.

As a result, the Aura study found, the mean gain in visual acuity after two years was 0.6 eyechart letters. For patients who did not receive a loading dose of three in the first 90 days, visual acuity actually fell below baseline after about a year.

The age of the population receiving treatment for wet AMD – the average age in Aura was 77 – means that illness, transportation and other aging-related barriers can make it difficult for patients to attend appointments. On top of that, the intravitreal injections themselves are burdensome, requiring anaesthesia, a sterile field and pre and post-treatment monitoring; if patients have AMD in both eyes the process must be done separately for each eye.

This is why Eylea, with its longer eight-week dosing interval, was considered a step forward in treatment, and why it represents the biggest drug budget line in the US Medicare programme’s part B at $2.2bn, or $10,500 a patient, in 2016. Regeneron has not given up on its ambitions to get a quarterly dosing schedule approved – if this does get the go-ahead it will make Eylea even more convenient.

Not a rarity

With gene therapies premiering with high six-figure price tags, investors might hope that Regenxbio will be able to do the same with RGX-314 – after all, the first gene therapy to be launched in the US, Spark’s Luxturna, for a rare inherited form of blindness, is going for about $700,000 a patient.

This is not a reasonable expectation for RGX-314, however.

For one, Luxturna is in a rare genetic disease, RPE65 mutation-associated retinal dystrophy, that affects an estimated 1,000-2,000 US patients in the US and often has onset in childhood. The Institute for Clinical and Economic Review suggested that a $755,633 price would meet a “value-based” benchmark if treatment is received at age 3, partly because it estimated that Luxturna would help patients gain 26 blindness-free years, eight more than the standard of care.

AMD, on the other hand, is a common disease, with nearly 317,000 Medicare beneficiaries having received treatment with either Eylea or Lucentis in 2016. Given the average age in the Aura study and a life expectancy of 10-12 years for patients of that age, neither the biologicals nor RGX-314 can hope to deliver the number of blindness-free years that Luxturna can.

The sweet spot

Moreover, payers will almost certainly want patients to try Eylea or Lucentis first before progressing to treatment with a gene therapy. The US government signalled last week that it would allow privately run Medicare Advantage plans to engage in “step therapy” – requiring patients to fail on cheaper drugs first – and with drug prices in the crosshairs the entire programme will likely embrace this (Biosimilars the beneficiary of new Medicare step therapy rule, August 9, 2018). In Europe this will also be the case.

Finally, pharma companies are looking beyond injections to make the biological agents work better. For example, Roche last month revealed results for a port delivery system that will allow patients to go six months between doses of Lucentis.

“That’s going to be the main competitor,” Professor Campochiaro said.

He reckons that Regenxbio has a good chance of reaching a price tag that is acceptable for payers, given that the production costs of this gene therapy are “not huge” – thought to be down to relatively low amounts of vector used. And should RGX-314 be able to demonstrate a durable benefit, for example for five years or more, a price in the hundreds of thousands of dollars might not look especially greedy.

“The fact that you can get potentially better outcomes and many fewer patient visits – those are advantages,” said Professor Campochiaro. “Hopefully they’re going to realise that there’s going to be a sweet spot.”

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