The U.S. Food and Drug Administration has recommended Kolon TissueGene to remanufacture the second fluid of Invossa-K if the company wishes to resume the phase-3 trial on the drug. Invossa-K, a genetic treatment for osteoarthritis, was suspended in Korea due to the mislabeling of the ingredient in the second fluid.
Kolon TissueGene said the remanufacturing was not a requirement for the trial resumption. Observers said, however, the company will find it difficult to ignore the FDA’s additional recommendation, observers said.
The Korean biotech firm publicly disclosed on Monday that it had received an official letter, “Continue Clinical Hold,” from the FDA, meaning that the company should hold the phase-3 trial on Invossa until the FDA approves the trial resumption. The FDA letter was a reply to Kolon TissueGene’s submission of data as previously required by the U.S. regulator on Aug. 23.
In the official letter, the FDA mentioned two lists – one with data that must be submitted for the resumption of the trial, and the other with an additional recommendation not specified as a reason for suspending the trial.
The required data is for the analysis on additional traits of the investigational drug ingredients, which includes chondrocytes traits data from Invosa’s first fluid, data analysis of gag/pol gene sequencing of the second fluid of Invossa, and confirmation of retrovirus generation after the introduction of env genes into the second fluid cells before and after irradiation.
Kolon TissueGene had submitted to the FDA the analysis on the characteristics of the first fluid of Invossa, but the FDA demanded more details in the data. The FDA did not request additional data on why the cell ingredient was different in the second fluid or any clinical data submission related to tumor risk.
The FDA recommended anew the remanufacturing of the second fluid (TC) from the first fluid (HC), for the most favorable benefit/risk product profile. In other words, as the second fluid contained kidney-derived (HEK-293) cells that should have been filtered out, it would be better to remanufacture the second fluid, according to the FDA.
The FDA also recommended Kolon TissueGene to have a long-term follow-up on every adverse reaction, instead of the company’s plan for long-term safety evaluation submitted on Aug. 23.
“The recommendation was not mentioned as a reason for holding the clinical trial. So, it is not a requirement for the trial resumption,” an official at Kolon TissueGene said.
However, the company will find it difficult to ignore the FDA’s recommendation just because it is not a requirement. In August, Kolon TissueGene submitted both required and recommended data to the FDA. It would be best for the company to reflect the FDA’s notes fully, observers said.
“The FDA cited the most favorable benefit/risk product profile as the reason for recommending the remaking of the second fluid. So, even if the remanufacturing is not a requirement, the FDA could take an issue with it during the approval process,” an expert in cell therapies at a biotech firm said. “If that’s the case, the company can resume the trial but may fail to win approval.”
The FDA’s request -- to check retrovirus generation after introduction of env genes into the second fluid cells before and after irradiation – is not an easy task, either.
“We can provide additional data requested by FDA fully through additional experiments in the future,” an official at Kolon TissueGene said.
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