[BioNOW] What is 'IDMC' that Helixmith is Waiting For...

Midterm Clinical Evaluation by 'Independent Monitoring Committee'
Recommendations on Clinical Continuation, Design Modification, and Discontinuation

[Asia Economy Reporter Chunhee Lee] There has been significant buzz in the bio industry since this Tuesday. The news is that the receipt of the interim evaluation by the Independent Data Monitoring Committee (IDMC) for Helixmith's gene therapy drug 'Engensis (VM202)' Phase 3-2 clinical trial has been delayed. At a press conference, CEO Sunyoung Kim mentioned 'submission of additional data' as the reason for the delay, which caused the stock price to plummet temporarily. However, CEO Kim later explained that as they reviewed the data, some inconsistencies naturally arose, and the additional data was requested for that reason, which helped reduce the stock price drop.

Although the IDMC is a U.S.-based organization, it has recently drawn much attention domestically as it has issued recommendations regarding clinical trials for Hanmi Pharmaceutical's non-alcoholic steatohepatitis (NASH) treatment new drug 'LAPSTriple Agonist' and Samchundang Pharmaceutical's 'Ailia' biosimilar 'SDC411'. So, what exactly is the IDMC, and what kind of recommendations does it make regarding clinical trials?

Clinical Trials Can Take Up to 10 Years... What If You Could Score Them Midway?

First, the name IDMC itself reflects its role. The full name is 'Independent Data Monitoring Committee.' It is a committee that independently monitors clinical trial data midway. But why is mid-trial monitoring necessary? This is because clinical trials consume enormous costs and time.

Once a drug moves beyond the non-clinical or preclinical stages, where it is administered to cells or animals, to human administration, clinical trials begin in earnest and become quite complex. Patient recruitment is necessary, and by the time it reaches Phase 3?the final stage before commercialization?large-scale trials involving 3,000 to 4,000 participants across multiple countries including Korea, the U.S., and Europe are required for global market entry. Naturally, this entails huge costs and time, and it is also necessary to monitor any adverse effects after the trial. Some Phase 3 trials can take over 10 years. From the perspective of the drug developer, this is a significant burden, and from the patient's perspective, there is also concern about receiving drugs whose safety and efficacy have not yet been fully verified.

Overview of IDMC's Interim Recommendation on Helixmith's 'Engensis (VM202)' Phase 3-2 Clinical Trial / Photo by Lee Chunhee

But what if it were possible to predict the success or failure of a clinical trial while it is ongoing? If the likelihood of failure is high, it could save additional costs and time and reduce patient risk. Also, the design of the ongoing trial could be adjusted to increase the chance of success. This is why the IDMC's interim recommendations are important.

However, such predictions cannot be made by just anyone. Clinical trials are basically conducted as double-blind studies. In cases where the experimental group receives the actual drug and the control group receives a placebo or comparator such as saline or vitamins, a 'blinded trial' is conducted to prevent the placebo effect (where patients believe they are receiving the drug and thus show effects). Moreover, if the doctors administering the drug know which patients are receiving the actual drug, it could bias the trial results, so the doctors are also blinded in a 'double-blind' setup. Therefore, neither the patients, doctors, nor the drug developers know who is receiving which treatment.

However, the IDMC has access to this blinded information. They can remove the masking on the data to see which patient received which drug and what effects occurred. For this reason, the IDMC is composed of independent members with no conflicts of interest.

The Three Paths Recommended by IDMC: Continue, Modify, or Stop

Based on the collected data, the IDMC usually issues one of three recommendations: 'continue the trial,' 'modify the trial design,' or 'stop the trial.' For example, the Engensis Phase 3-2 trial is currently underway with 152 participants. The IDMC's recommendation is expected to be one of the following: 'continue with 152 participants,' 'adjust the number of participants (up to 250),' or 'stop the trial.'

The recommendation is based on the 'conditional power' calculated from the data secured and analyzed by the IDMC. If the conditional power is 80% or higher, the trial continues as planned; if it is between 39.6% and 80%, the IDMC recalculates and notifies the required number of participants; if it is below 39.6%, the IDMC recommends stopping the trial.

Previously, Hanmi Pharmaceutical's 'LAPSTriple Agonist' received two consecutive 'continue trial' recommendations from the IDMC in October last year and May this year, and Samchundang Pharmaceutical's 'SCD411' also received a recommendation to continue. Sometimes, the IDMC recommends early termination of a trial if the drug shows outstanding efficacy. For instance, AstraZeneca's lung cancer drug 'Tagrisso' was recommended for 'early unblinding' by the IDMC during its global Phase 3 trial in 2020 due to its 'remarkable efficacy.'

On the other hand, the IDMC may recommend stopping a trial. In 2019, Transgene, the European partner of SillaJen developing Pexa-Vec for liver cancer treatment, halted the trial following an IDMC recommendation to stop.

However, the IDMC's interim recommendations are just that?recommendations. Since they are based on interim data, there are inherent limitations. Even if the IDMC recommends continuing the trial, the final data may fail to meet the set goals (endpoints), or serious adverse effects may suddenly appear after the interim data analysis. Conversely, even if the IDMC recommends stopping the trial, analysis and follow-up management of participants who have already been dosed continue, and unexpected successful outcomes may emerge during this process.