Whether Yuhan Corp.’s new lung cancer treatment Leclaza (lazertinib) succeeds will depend on how the company can verify its safety and address the ethical issue in an upcoming phase-3 local study, experts said.

The Ministry of Food and Drug Safety released minutes of the Central Pharmaceutical Affairs Advisory Committee (CPAC) meeting on granting conditional approval for Leclaza.

The virtual CPAC meeting took place on Dec. 28, gathering nine experts from the new drug sub-committee and smaller clinical trial policy sub-committee, and six ministry officials.

The minutes showed that all of the CPAC members agreed to grant a conditional nod for Leclaza.

The most discussed topic was the safety of the new drug.

Yuhan Corp.’s new lung cancer treatment Leclaza (lazertinib) still has to resolve the safety issue in a phase-3 clinical trial, experts said. (Yuhan)
Yuhan Corp.’s new lung cancer treatment Leclaza (lazertinib) still has to resolve the safety issue in a phase-3 clinical trial, experts said. (Yuhan)

During the meeting, one panelist asked whether the ministry made the right call that Yuhan did not have to suspend the trial even though suspected unexpected serious adverse reactions (SUSAR) included a death during the trial.

In response, a ministry official said, “We confirmed that one case was directly related to the treatment, and the other 3 cases were not directly related. We also confirmed that there were no additional issues in the meeting regarding the report of adverse reactions.”

Since the development stage, Leclaza has not been free from drug-induced QT prolongation or delayed heart recharging between beats. However, the ministry official said Leclaza was less toxic than the comparative drug Tagrisso (osimertinib) in terms of QT prolongation.

“Judging based on the submitted data, we cannot say that Leclaza has no toxicity related to QT prolongation. But, it appears to be less toxic than that of the comparative drug,” the official said.

Another panelist raised concerns over the safety management of Leclaza, citing its similarity to Olita (olmutinib), an EGFR(Epidermal Growth Factor Receptor)-TKI(Tyrosine kinase inhibitor) that Hanmi Pharmaceutical had given up developing. Hanmi had obtained conditional approval for Olita but dropped the development program due to serious adverse reactions.

The ministry official said the ministry was aware of Leclaza’s similarity to Olita. Still, it reviewed the issue during the evaluation of the company’s risk management plan (RMP) after the market launch.

“We agree that we need measures to prevent adverse drug reactions. We will include this issue in the safety-related matters,” the official added.

According to the minutes, Yuhan will conduct a confirmatory phase-3 study in Korea.

One CPAC member noted that giving chemotherapy to lung cancer patients in the control group in a phase-3 study could cause ethical issues because osimertinib, a better drug than chemotherapy, is already covered by health insurance in the second-line treatment. “We need to come up with a plan to address this issue,” the panelist said.

The ministry official said the ministry would reflect the opinion when approving a phase-3 study. As the company also plans to conduct a global trial, the ministry will analyze the worldwide trial results even if the data would be from other races for safety verification, the official said.

“After receiving consultation, we concluded that giving approval for Leclaza on the condition that the company submits phase-3 trial results later was a reasonable decision,” the official went on to say. “We will take into account the safety issue coming from a small number of trial participants when we set conditions for the submission of the phase-3 study plan.”

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