Hanmi Pharmaceutical's oral anticancer drug, Oraxol, faced a temporary setback in its approval process after the U.S. Food and Drug Administration sent a complete response letter (CRL) to Athenex, Hanmi’s U.S. partner.

Hanmi's U.S. partner, Athenex, has run into an obstacle in launching Oraxol, an oral anticancer treatment, in the U.S. by receiving a letter from the FDA to supplement its application. (Hanmi)
Hanmi's U.S. partner, Athenex, has run into an obstacle in launching Oraxol, an oral anticancer treatment, in the U.S. by receiving a letter from the FDA to supplement its application. (Hanmi)

The FDA issues a CRL to indicate that the review cycle for an application is complete and that the application is not ready for approval in its present form.

The news comes after Hanmi expressed high expectations on receiving product approval for the treatment this year at the JP Morgan Healthcare Conference in January. The drug received a priority review designation from the FDA in September last year.

According to Athenex, the FDA has issued a CRL for the company's new drug application (NDA) for oral paclitaxel plus encequidar to treat metastatic breast cancer. In the CRL, the FDA indicated its concern about patients' safety risk regarding an increase in neutropenia-related sequelae on the oral paclitaxel group compared with the IV paclitaxel group.

The U.S. regulator also expressed worries regarding the uncertainty over the results of the primary endpoint of objective response rate (ORR) at week 19 conducted by blinded independent central review (BICR).

The FDA stated that the BICR reconciliation and re-read process might have introduced unmeasured bias and influence on the BICR.

Accordingly, the FDA advised Athenex to conduct appropriate new clinical trials in patients with metastatic breast cancer in the U.S. to evaluate additional safety data and the need for additional strategies to improve safety, such as optimizing dosage.

Athenex plans to request a meeting with the FDA to discuss the agency's response, engage in a dialogue on the design and scope of a clinical trial to address the FDA's requirements and align the next steps required to obtain approval.

Despite Athenex’s efforts, Hanmi admits the drug is unlikely to receive sales approval this year as expected.

"While it is not decided yet whether Athenex will have to run additional clinical trials or submit supplementary data, the company's expectation on receiving U.S. approval for Oraxol in the first half of this year is unlikely to become a reality with the FDA's CRL," a Hanmi official said to Korea Biomedical Review. "If Athenex has to conduct additional clinical trials, it may become difficult for Oraxol to receive an approval even within this year."

Athenex Chief Medical Officer Dr. Rudolf Kwan also said, "Our clinical and regulatory teams are disappointed by the CRL."

However, the company plans to work with the FDA to resolve the CRL issues and obtain approval for oral paclitaxel plus encequidar in metastatic breast cancer, he said.

With the FDA's CRL putting a hold on the approval of Oraxol in the U.S., it has also become unlikely that Hanmi will receive the milestone payment for product approval from Athenex this year.

If Oraxol receives approval, Hanmi will receive a $24 million milestone payment and royalties based on net sales from Athenex.

Oraxol is an oral dosage form of the widely used intravenous administered tubulin-stabilizing chemotherapeutic agent paclitaxel. The company licensed-out the drug to Athenex in 2011.

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