Executive Summary

South Korea, which has recently delayed the political passage of a cutting-edge regenerative medicine and biologics act, should learn from the latest unprecedented incident involving Kolon Life Science’s cell and gene therapy Invossa, and pre-emptively make preparations and guidelines to better deal with such pioneering medicines, an industry expert tells Scrip. 

Trial and error is frequently, if not always, an accompaniment to the introduction of new technologies. As one example, in South Korea there was huge controversy a decade ago relating to a stem cell research scandal involving a local cloning scientist.

Gene therapies have also been controversial as the approach was seen by some as "playing god", and concerns over the safety and bioethics of such cutting-edge therapies have been raised worldwide as technology has yet to stabilize. 

However, it remains a fact that global pharma firms will continue to race towards the development of these and other pioneering approaches, and against this background, South Korea should actively pursue and even lead the development of these drugs to become a major player, according to one local observer.

New Technologies Come With Trial And Error

In this regard, Kolon Life Science Inc.'s gene therapy Invossa (TG-C) may be just another example of the trial and error involved in the development of novel medical treatments, Yun-Taek Jung, president of South Korea’s Pharmaceutical Strategy Institute (PSI), said in an interview with Scrip.

The first approved gene therapy in the country, Invossa was recently suspended from sale and distribution in South Korea, while recruitment in an ongoing US Phase III trial program has been temporarily halted, following findings that an active cell component may differ from the data submitted at the time of approval.

Korea Suspends First Approved Gene Therapy Pending Component Discrepancy Probe

South Korea’s first approved gene therapy has been suspended from sale in the country, while recruitment in an ongoing US Phase III program has been temporarily halted, after findings that an active cell component may differ from the data submitted at the time of approval. While both manufacturer and regulator see no safety risk, results from an official Korean probe ...

“The latest unprecedented incident could just be limited to this company’s issue. It could just be an issue of the difference in technology advancement between 2004 and present, or an error that is now unveiled, or could be another issue,” commented Jung. “In any case, there is definitely trial and error in such a new technology.”

South Korea’s drug authorities are slated to disclose the result of their ongoing probe into the product in mid-April, while the FDA in the US is to discuss the matter with the company.

Invossa, approved in South Korea in 2017, has been under the spotlight due to the advancement to commercialization of a gene therapy and its use of advanced technology, although it did not get the disease-modifying status Kolon had hoped for. The company is instead aiming to establish this in the Phase III US trials.

Cutting-Edge Biologics Law Delayed

A recent delay in the political passage by parliament of a new act to support and ensure the safety of cutting-edge regenerative medicines and biologics may also have been directly or indirectly affected by the Invossa incident, given that this is likely to have raised concerns over such innovative therapies.

The bill for the proposed act aims to give priority to the review of biologics for treating rare diseases, and to grant conditional approvals to such drugs once their efficacy is sufficiently proven. Such a system usually involves the postmarketing surveillance of safety and efficacy in actual use for a certain period before a full approval is given.

South Korea has also been trying to come up with detailed guidelines for a fast-track review and approval system to provide the industry with a clearer understanding of the process, as it has been unclear which medicines are eligible for the scheme and how this actually works in practice.  (Also see "Korea To Introduce Fast-Track Review For Cutting-Edge Biologics, Devices" - Pink Sheet, 25 Jan, 2018.) 

Need For Clearer Guidelines

Although gene therapies may require continued long-term monitoring to determine possible side-effects, so far Kolon’s clinical trial and real world data for Invossa in more than 3,400 patients over the past 11 years do not point to any major safety issues or risks.

“New therapies will continue to face various challenges and there will certainly be trial and error in the beginning. But based on this experience [with Invossa], new therapeutics should continue to be developed,” Jung stressed. “The parliament is saying that more discussions may be needed to pass the cutting-edge biologics act, but it is essential to act pre-emptively to prepare and establish these guidelines.”

If South Korea can have clearer guidelines on the development of pioneering drugs, this could help authorities better deal with these and lead to more stable results in granting their approvals, he said.

Jung pointed to the 21st Century Cures Act in the US and the Regenerative Medicine Act in Japan as examples of efforts to get in a better position to handle new technologies. “These laws were also introduced for the safety management of these drugs and such laws support both the industry and regulators in these countries, but not in South Korea,” he noted.

This may not mean that South Korea's ministry of food and drug safety handled the approval of Invossa inappropriately, Jung observed, but the incident will be further reviewed and investigated by the ministry and the US FDA to make more precise judgments and decisions. It appears that the discrepancies in cell type may not have been confirmed just by the approval documents submitted to the ministry, the PSI president said.

“What it [the Invossa affair] suggests is that this should be a good opportunity for South Korea to learn from this experience and better handle such issues going forward, as more and more cutting edge medicines are developed and launched in the country,” Jung said.

PSI, a pharma industry research and consulting institute in South Korea, provides solutions across the pharma value chain to support the advancement of the industry into the global market, and enhances new drug development capabilities by exploring innovative and sustainable business models. Jung is also an adjunct professor of the department of pharmaceutical industry at the country's Chung-Ang University.

From the editors of PharmAsia News.