To Ocugen CEO Shankar Musunuri, Ph.D., most gene therapy biotechs today lack vision. Rather than focusing on rare diseases with small patient populations, as Musunuri sees it, these companies should widen their aperture to conditions that affect much larger numbers of people.
Such is the strategy Ocugen is pursuing, with plans to file three products for approval over the next two years in inherited forms of vision loss, Musunuri explained to Fierce Biotech in an interview earlier this month.
“We cover the breadth and depth that takes care of the majority of the unmet medical needs in retinal diseases today,” the CEO said.
“Vision loss diseases are costing our economy $134 billion a year,” according to Musunuri, with the main contributors being retinitis pigmentosa (RP), Stargardt disease and age-related macular degeneration (AMD). “We're working on all three of them,” he said.
OCU400, Ocugen’s gene therapy candidate for RP, is the furthest along, with a phase 3 trial underway and plans for a rolling submission for FDA approval to begin this year, Musunuri said. With 140 patients enrolledm he described the study as the “largest orphan gene therapy trial in the world.”
Should OCU400 secure approval, it wouldn’t be the first gene therapy for RP, a disease marked by steady degradation of the retina in the back of the eye. That honor goes to Luxturna, which secured approval in 2017 under Spark Therapeutics before the company's $4.3 billion buyout by Roche two years later.
However, Luxturna only works for patients whose disease is caused by mutations in both copies of the RPE65 gene, which accounts for around 1% to 6% of all RP cases.
“Defects in over 100 genes can cause RP,” Musunuri said. “So if you take Spark’s approach, you need 100 products.”
With a goal of addressing all patients affected by RP, Ocugen is wisely not trying to develop and commercialize 100 different gene therapies. Instead, OCU400 is designed to deliver a gene called NR2E3, which is a master regulator that controls the expression of countless other genes. By bringing NR2E3 into the retina, Ocugen hopes to restore balance to the eye and save vision.
It’s the same approach the Philadelphia-area biotech is pursuing for Stargardt disease and geographic atrophy, an advanced form of dry AMD—one-time injections that can treat, if not outright cure, disease in as many patients as possible.
“FDA doesn't give a label ‘cure,’ they give a label of treatment,” Musunuri explained. “So, I call them one-time treatments. It's potentially for life.”
OCU400 is closely followed by OCU410ST in Stargardt disease and OCU410 in geographic atrophy. Ocugen recently posted a phase 2 win in geographic atrophy, and now plans to launch a phase 3 trial with as many as 300 patients later this year.
In Stargardt disease, which causes vision loss in children and young adults, Ocugen is running a phase 2/3 trial that should read out data later this year.
There are currently no approved gene therapies that treat Stargardt disease or dry AMD. Because all of Ocugen’s trials are running for one year, with the FDA’s blessing, Musunuri hopes to quickly commercialize the biotech’s gene therapies should the studies succeed.
“We have three BLAs we're targeting in the next two years,” Musunuri said. “That should take care of most of the vision loss diseases today with unmet medical needs.”
Because Ocugen’s therapies can be administered directly into the retina, doses can be relatively low compared to systemic gene therapies, which makes manufacturing cheaper. This, in turn, means the company plans to not charge the onerous prices that have long marked gene therapy.
“We don't have to charge $4 million or $3 million,” Musunuri said, “and then when we get to the market, we have [a] large patient population, so that will allow us to be commercially successful.”
Other gene therapy outfits have focused on technical success, the Ocugen leader told Fierce, targeting single genes that can maybe treat worthy, but small, rare disease patient populations. Here, even success can’t guarantee a company’s survival.
“I've been in the industry for over 35 years now, so I can tell you, if you don't have a billion-dollar product, the market doesn't pay attention to it,” Musunuri said. “They think you're a failure commercially.”
So what should all the biotechs pursuing gene therapies for rare diseases do? Band together, Musunuri thinks, pointing to Roivant’s approach as an example.
“If they're smart enough, they should all merge,” he said, to form a conglomerate focused on 20 or 30 products. “If they have one or two products, they won't survive.”
For Musunuri, another key to success is not getting too big for your britches. That’s why Ocugen is now dead set on ophthalmology. But should the company’s trio of products make it to market, he already has the next therapeutic area in mind for the master regulator approach.
“We believe our genes will work in neurodegenerative disorders,” he divulged, like autism and Alzheimer’s disease. “That's the next frontier for us. We as a company want to be disciplined, master ophthalmology, then go into different disease areas.”