Johnson & Johnson dips a toe into gene therapy

A deal between J&J and Meiragtx in eye disease shows growing interest from big pharma as gene therapy's commercial issues come into focus.

Johnson & Johnson has joined Novartis and Pfizer as a big pharma gene therapy player, licensing three eye disease programmes from Meiragtx for $100m, and pledging to fund clinical development and commercialisation activities.

Meiragtx has several mid-stage assets, but so far its inherited retinal disease candidates have not drawn the same level of attention as projects from the likes of Spark, Ultragenyx or Nightstar. The J&J deal could change this. Eye disorders lie outside J&J's usual focus, but gene therapies targeting the eye could have biological advantages over those for muscular conditions or blood disorders, for example.

Expanding a partnership

Still, the commercial outlook for gene therapies is unclear at best. For J&J, this is a relatively small bet, but it looks like a good deal for Meiragtx, the gene therapy business spun out from the then privately held Kadmon in 2015. In addition to the up-front payment and development funding, $340m in milestones and a 20% royalty are on offer.

The deal builds on an existing research collaboration between the two companies, covering preclinical gene therapies that can be regulated using a small-molecule as an on/off switch. The main agreement signed yesterday involves three AAV gene therapies modulating expression in two disorders: achromatopsia and X-linked retinitis pigmentosa.

The two achromatopsia assets target CNGB3 and CNGA3 mutations, which have patient populations of about 5,000 and 2,000 respectively. Unlike trials of gene therapies in sickle cell disease and haemophilia, Meiragtx is enrolling all-comers rather than subgroups because of the severity of the disease (Tiny populations up the ante for gene therapy pricing, December 20, 2018).

“This is a severe disease where all patients are born legally blind,” Meiragtx's chief executive, Alexandria Forbes, told Vantage. “They have photoaversion. Rather than seeing daylight they feel pain.”

Meanwhile, the X-linked retinitis pigmentosa gene therapy seeks to modulate mutations in RPGR open reading frame 15, one of the less common causes of a condition that affects around 20,000 Americans. 

Reasons to make a deal

The fact that the very first gene therapy to earn approval in the US, Luxturna, treats an ophthalmological condition might prompt some optimism about Meiragtx’s projects. Ms Forbes said inherited eye disorders provided a good hunting ground for gene therapy developers, in part because there are around 300 such conditions, collectively affecting 200,000 Americans.

Selected gene therapies for eye diseases
Product Company Pharma class 2024 sales forecasts ($m) Status
NSR-REP1 Nightstar Therapeutics AAV encoding REP1 gene therapy 371 Phase III
SPK-7001 Spark Therapeutics Rab escort protein 1 gene therapy 353 Phase II
RGX-314 Regenxbio Retinitis pigmentosa GTPase regulator gene therapy 257 Phase I
Luxturna Spark/Novartis RPE65 gene therapy 325 Marketed
NSR-RPGR Nightstar Therapeutics RPGR gene therapy 125 Phase II
Allergan-Editas Medicine Eye Disease Program Editas Medicine Gene therapy 120 Research project
Source: EvaluatePharma.

“When you think about that population there’s a huge synergy in clinical development and commercial development,” she says. “These patients see the same physicians, go through the same assessments. To be a viable endeavour we wanted to approach this not as a single indication but as a group of indications.”

The eye has other advantages, she added. As an immune-privileged organ there is less concern over an inflammatory response; this is something that has troubled Spark’s haemophilia A project, which has led to the company amending a trial to include treatment with prophylactic steroids (To stem the bleeding Spark's pivotal trial needs to catch fire, August 18, 2018).

Finally, being a compartmentalised organ the eye needs fewer viral vectors to stimulate a therapeutic response. To this end, Ms Forbes says Meiragtx has already developed enough manufacturing capacity to meet commercial demand as well as clinical needs.

Yesterday's deal also includes a manufacturing component; in addition, J&J is collaborating on Meiragtx's preclinical candidates for inherited retinal diseases. Meanwhile, Meiragtx will retain rights to its candidates in other disorders, including mid-stage projects in xerostomia and Parkinson's disease. 

The advantages for ocular gene therapies do not seem to be lost on investors. Nightstar, which like Meiragtx is heavily focused on eye diseases, saw its shares rise 6% yesterday off the back of a 30% rise in Meiragtx’s.

Living up to the expectations now set for the gene therapy sector is going to be hard, as questions over matters like uptake, durability and payer acceptance have yet to be resolved. In Meiragtx’s eye-disease candidates, J&J is placing a very careful bet, and one that has a persuasive rationale supporting it.

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