Pharmaceutical industry observers are closely following whether Kolon Life Science and its subsidiary Kolon TissueGene will pull off successful clinical trials on Invossa-K, gene therapy for osteoarthritis, in the United States.
After the Korean regulator nullified the license of Invossa due to a drug mislabeling last year, how Kolon will conduct the U.S. studies and regain trust in the medicine will be the key issue.
Kolon registered two phase-3 trials of Invossa on ClinicalTrials.gov, an online site providing U.S. clinical trial information. Both trials will test Invossa in 510 patients with moderate or severe knee osteoarthritis with Kellgren & Lawrence Grade 2 or 3.
The first phase-3 trial, which was suspended during patient recruiting, set the primary endpoint as changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analog Scale (VAS) at 12 months.
The secondary endpoint is related to cartilage regeneration measured by Joint Space Width (JSW) and MRI assessments at 12 months.
Regarding the issue, Kolon Life Science had said that it hoped to prove Invossa’s disease-modifying osteoarthritis drug (DMOAD) effect by showing structural improvement of joint tissues or inhibition of disease progression.
The second study targets the same number of participants and primary and secondary endpoints but sets the evaluation at 24 months. The study has yet to begin.
What is risk-to-benefit ratio in Invossa trials?
Aside from the safety issue of Invossa’s ingredient, the drug showed higher International Knee Documentation Committee (IKDC) scores in the primary endpoints, including joint pain and physical function.
Invossa’s IKDC scores were up 15.1 points from the baseline, significantly higher than the 5 points in the placebo group in a local trial. However, the local study tested the drug in a small pool of 163 patients, while the U.S. trials will administer the medication to 1,020 patients.
Kolon will have to prove that Invossa can demonstrate meaningful improvements in large-scale U.S. studies. Unlike the local trial, the U.S. trials will also include patients with moderate symptoms (Grade 2), which will affect the trial outcomes.
Another critical point is whether Invossa can prove efficacy as a DMOAD. In the local trial, the drug failed to show meaningful structural improvement in damaged cartilage in MRIs in the comparison between the treatment group and the control group. The company will have to demonstrate the drug’s cartilage regeneration effect in the U.S. trials.
Kolon will also have to prove a clear benefit that overrides a significant risk of gene therapy, which involves injecting transduced cells.
As much time has passed since the beginning of the trials, the company might revise the clinical designs of the studies partially.
"We want to resume the trials within this year. We will have to see whether to keep the clinical design or change it for the time being," an official at Kolon Life Science said.
Kolon TissueGene on verge of delisting becomes new risk
Kolon TissueGene, the developer of Invossa, has become a new risk for Kolon Life Science because Kolon TissueGene is facing the regulator’s delayed decision on delisting.
The Korea Exchange put the firm for a delisting review twice. Last year, the KRX said it would consider delisting the firm after finding that Kolon TissueGene falsely reported or missed important information about Invossa.
The regulator gave the company a one-year grace period, but the company received a disclaimer of opinion from an auditor in the 2019 business report. The unclean audit report put the company under a delisting review again.
Kolon TissueGene did not use the KRX’s "technology exception policy" to go public on the Kosdaq market. The policy makes listing easier for companies with exceptional technological power.
If a customarily listed company reports operating losses for four consecutive years, the company can face the designation of an administrative issue. If the company continues to report operating losses the next year, the regulator will review delisting the firm.
Listed in 2017, Kolon TissueGene has been recording operating losses for three consecutive years. It is highly likely that the company might face the risk of delisting in the middle of the U.S. trials of Invossa.
Last year, Kolon TissueGene sought to be exempted from the strict financial regulations using the exception policy for biotech firms designated as administrative issues. However, the Invossa recall and the revocation of the license made such efforts worthless.
As Kolon TissueGene is also undergoing criminal trials on charges of violating the Capital Markets Act involving the winning of the Invossa license, the company will have to search for other ways to conduct the U.S. trials as scheduled.