NeoCart's Revival Continues as FDA Approves Ocugen's Phase III Trial Design (Updated)

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The FDA has approved the Phase III trial design for Ocugen's NeoCart, the company announced Friday. It's the next step in a possible redemption story for the regenerative cell therapy. 

NeoCart joined the company’s list of assets when Ocugen scooped up a struggling Histogenics in a 2019 reverse merger. The deal gained Ocugen publicly traded status and a regenerative cell therapy for the repair of full-thickness lesions in knee cartilage.

Histogenics completed a Phase III trial of the therapy, comparing efficacy to microfracture surgery, a common procedure to repair damaged knee cartilage. NeoCart failed to meet the trial’s primary endpoint to improve function and pain over a year versus patients treated with microfracture.

Histogenics went forward with its BLA submission - until the FDA demanded more data. With a limited cash runway, the company dropped the program while still believing the therapy had potential.

“They just very narrowly missed it,” Ocugen CEO Shankar Musunuri, Ph.D. told BioSpace in an interview.

He pointed to the use of microfracture as the comparison, when surgeons are “not big fans of microfracture” so recruitment is small. A posthoc analysis also revealed that using a slightly larger lesion size, the trial would’ve passed.

NeoCart found its revival in Ocugen, when the FDA granted the asset Regenerative Medicine Advanced Therapy designation this spring. The agency has now agreed to Ocugen’s proposed design for a new Phase III study.

Learning from the Histogenics trial, Ocugen will test NeoCart against the current standard of care, chondroplasty, for patients with articular cartilage defects.

“This is a great technology. Nobody has this technology platform,” Musunuri said. He pointed to a competitor on the market, Vericel Corp., which also engineers patient tissues on a scaffold. But, “They don’t grow it like we do – 3D.”

While a chondroplasty procedure goes into the knee to trim damaged cartilage and remove loose fragments to promote healing, NeoCart intends to rebuild patients' damaged knee cartilage.

A three-dimensional disc of new cartilage is grown from the patient’s own chondrocyte cells. By merging with the patient’s cells, the design hopes to accelerate healing and reduce pain better than standard of care.

“What takes your body one year [growing chondrocytes], we can do in less than two weeks," Musunuri said.

Ocugen will file an IND amendment to initiate the Phase III trial in late 2023/early 2024, according to Friday's press release. The biotech also announced it is building a GMP cell therapy manufacturing facility to support the manufacturing process for the cell therapy.

A Diverse Portfolio 

In addition to NeoCart, Ocugen's diverse pipeline includes two COVID-19 vaccines and three gene therapies targeting its original focus – eye disease.

Excitement over Covaxin, Bharat Biotech’s inactive COVID-19 vaccine for which Ocugen is a US partner, fizzled when the FDA declined to grant an EUA for the jab, asking for a BLA instead.

To date, Ocugen has only been able to get the shot authorized in Mexico. It is currently in a Phase II/III trial in the U.S.

Ocugen’s second vaccine candidate uses intranasal delivery to generate local mucosal immunity. The idea is to increase accessibility with non-invasive, needle-free administration, while also lowering transmission rates, an area where mRNA vaccines have fallen short. Mucosal vaccines against SARS-CoV-2 have been approved for use in India and China.

On Thursday, the FDA granted orphan drug designation Ocugen's gene agnostic modifier gene therapy, which can target multiple retinal diseases.

“What we have is that one gene, a modifier gene, that controls the entire functional network, and all underlying gene expressions. It resets homeostasis at the cellular level," Musunuri explained. "It has the potential to treat all these priorities with a single product." 

Musunuri, who came to Ocugen from Pfizer, compared the company’s diverse portfolio to that of big pharma.

“The technology is pretty similar, actually," he said, "There is a lot of knowledge your R&D team and manufacturing teams develop. We have that foundational platform. Now, all we're doing is integrating it into different disease areas."  

If NeoCart hits the mark in the clinic, it could be the company’s first substantial money-maker after years of research.