HONG KONG – South Korean biopharmaceutical company Kolon Tissuegene Inc. got a new lease on life as the U.S. FDA lifted the hold on the phase III trial for its lead candidate, Invossa-K (Invossa), for the treatment of osteoarthritis.

The company said it was informed by the FDA decision on April 11 in a letter in which the regulator said that Tissuegene had “satisfactorily addressed all clinical hold issues” and that the trials could resume. It also requested improvement plans in the production of culture containers reported as damaged in a Tissuegene annual report, as well as data from the stability test scheduled during the phase III trials.

A cell and gene therapy, Invossa treats osteoarthritis through a single intra-articular injection, which injects regenerative genes to cartilage cells, with pain relief potentially lasting up to two years.

It is the most advanced product in the Tissuegene pipeline and is touted as a novel therapy with blockbuster potential. Invossa was already available for sale in Hong Kong and Macau and was scheduled to be exported to Mongolia, Hainan, Saudi Arabia and the United Arab Emirates when the hold was issued.

Tissuegene had also inked an agreement totaling ₩500 billion (US$427.4 million) to develop and commercialize its therapy with Japan’s Mitsubishi Tanabe Pharma Corp. in November 2016. Under the contract, Tissuegene received an up-front payment of $24 million in addition to a $415 million milestone payment from the Japanese company.

The therapy then received marketing approval in South Korea from the country’s Ministry of Food and Drug Safety (MFDS) in July 2017.

Tissuegene got into trouble in March 2019 when it was revealed that one of the therapy’s ingredients was the potentially cancerous kidney-derived GP2-293 cells instead of the cartilage-derived cells that the company claimed to be using when it applied for the regulatory clearance.

The FDA implemented the hold on Invossa’s phase III trials on May 3, 2019, and South Korea’s MFDS revoked the marketing license the following month in the aftermath of the allegations.

A Tissuegene source said the FDA requested documents to address the issues with the drug in the letter announcing the clinical hold. The Korean company submitted the requested documents in August 2019, and the FDA later requested a second set of supplementary documents in September 2019.

A Sept. 23 Tissuegene press release listed three clinical hold-related issues and three non-clinical hold-related issues to be addressed in its documents. The FDA then removed the clinical hold once it examined the documents and determined that the issues were properly addressed.

The FDA declined to comment on Invossa’s case when contacted by BioWorld.

Tissuegene also delisted from the secondary KOSDAQ board in August as Invossa’s license was revoked. The company went public on the board in November 2017, with securities firm NH Investment and Securities acting as the lead manager while Korea Investment and Securities helped to arrange the deal.

Korea Exchange later slapped bans on the two firms in July 2019 from sponsoring foreign company IPOs until November 2020.

Tissuegene was also faced with lawsuits from disgruntled shareholders, partner companies and patients who had been injected with the drug. Trials for Kolon executives, including Kolon Life Sciences CEO Woo Sok Lee, are currently underway.

Mitsubishi terminated its agreement with Tissuegene after discovering the ingredient misnomer as it reviewed data from the drug. Subsequently, it filed a ₩26.2 billion complaint against the troubled Korean company with the International Chamber of Commerce in late 2017.

The Tissuegene source declined to comment on any legal actions.

“We’re now preparing to resume the phase III trials,” said the Tissuegene spokesperson, but also added that the COVID-19 pandemic and the necessary preparations involved made it difficult to predict when the trials could resume.

Founded in 1999, Maryland-based Tissuegene is the U.S. subsidiary of Seoul-based Kolon Life Sciences, which in turn is a subsidiary of the Kolon Group conglomerate. Kolon Life Sciences has also acted as Tissuegene’s Asian licensee since June 2000.

Kolon Life Science’s stock jumped almost 30% to ₩26,900 as markets opened on April 13 after the announcement. It was up 29.29% to ₩45,400 at market close April 16.

It remains to be seen whether the resumed trials, alongside the company’s mea culpa on its website, will help resurrect Tissuegene’s cash cow.

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