HONG KONG – China's Zai Lab Ltd. has returned the exclusive sales license of lung cancer drug Olita Tab (olmutinib) to its developer, South Korea's Hanmi Pharmaceutical Co. Ltd., a move Zai attributed to reprioritization, though Olita Tab has run into problems in clinical studies.

Shanghai-based Zai Lab previously held the sales right to Olita Tab in China, Hong Kong and Macau through a KRW90.52 billion (US$84.6 million) licensing deal. "We decided to return China development and commercial rights of olmutinib to Hanmi Pharmaceutical to prioritize our resources to other pipeline candidates. Zai Lab remains committed to advancing transformative drugs to treat oncology, autoimmune and infectious diseases," Jonathan Wang, vice president and head of business development at Zai Lab, told BioWorld. (See BioWorld Today, Nov. 25, 2015.)

"We will work closely with Hanmi to ensure a seamless transition of the responsibilities of the current olmutinib clinical development program back to Hanmi," he added.

Seoul-based Hanmi did not respond to BioWorld's queries regarding that development. However, industry observers have indicated the termination of the deal is most likely linked to problems Hanmi has faced over Olita Tab's clinical trials.

The Board of Audit and Inspection (BAI) of Korea recently revealed that Hanmi was found to have broken two medical laws, specifically regarding the monitoring and reporting of its clinical trials. However, no penalties were announced.

In March 2015, VHS Medical Center had signed a partnership to carry out clinical trials of Olita Tab in local lung cancer patients on behalf of Hanmi. Then in June 2015, a patient on the olmutinib trial showed symptoms of the life-threatening skin condition Stevens-Johnson syndrome (SJS).

The patient passed away from the complications the following month and the person in charge reported the incident to the authorities.

But Hanmi did not immediately report the SJS side effect to local health regulators until September 2016, something the company was supposed to do within 24 hours as per local regulations.

The BAI started an investigation after some lawmakers accused Hanmi of purposely delaying its reporting of the fatal side effect so it could gain approval for the drug during a parliamentary audit last year. But the board reported later that it did not find any evidence that Hanmi had attempted to delay the reporting.

Though Hanmi has since admitted to some "shortcomings" in its reporting protocols that led to the delay, it primarily blamed a misinterpretation of the side effect as the reason.

The pharmaceutical company explained that the patient who had shown symptoms of SJS was also taking two additional cancer medications, namely bromhexine and tiocra, both of which have known side effects that include SJS. Due to that, the staff involved had discerned and categorized the patient's SJS as a "serious event" that had been caused by the other two drugs.

Immediate reporting is only required when the case is categorized as "serious unexpected serious adverse reaction."

Hanmi claimed in a statement it had only become aware that the SJS incident in the patient was linked to olmutinib during the process of monitoring all of its clinical trial data a year after the event's occurrence. The company said it then immediately reported the findings to the South Korean Ministry of Food and Drug Safety (MFDS).

The fatal side effect had contributed to Boehringer Ingelheim GmbH's decision to terminate its $730 million licensing partnership with Hanmi over the lung cancer drug last year. Boehringer Ingelheim and Hanmi Pharmaceutical had signed an exclusive license agreement in 2015 to provide the German pharmaceutical company with worldwide exclusive rights, excluding South Korea, China and Hong Kong. (See BioWorld Today, Aug. 5, 2015, and Oct. 3, 2016.)

In May 2016, South Korea was the first country to approve olmutinib for the treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive non-small-cell lung cancer, who had been previously treated with an EGFR tyrosine kinase inhibitor.

The approval was based on the results of the phase I/II trial, which showed promising clinical activity for olmutinib. Among 69 patients evaluable for response, the objective response was observed by independent assessment in 62 percent of patients, including 32 (46 percent) whose tumor response had been confirmed at the time of data cut-off on June 30, 2015.

The MFDS had decided to uphold the drug's approval status in October 2016 after the complication was reported, with the caveat that patients are informed of the potential side effect when prescribed.