The government has accepted Bayer’s request to reduce the number of review cases of Stivarga (ingredient: regorafenib), a gastrointestinal stromal tumor (GIST) treatment, from 3,000 to 300 for the drug reevaluation.

Bayer’s gastrointestinal stromal tumor (GIST) treatment Stivarga

The Ministry of Food and Drug Safety held a meeting of the central pharmaceutical affairs advisory committee on Jan. 10 to decide whether to cut the number.

Bayer won the nod for Stivarga as a novel drug in Korea in 2013. Under the local regulation, a novel medicine’s supplier is required to conduct post-marketing surveillance (PMS) study on 3,000 patients during the six years of the reevaluation period and collect information on the safety of the drug.

However, Bayer failed to meet the required number and recently requested the food and drug Safety ministry to reduce the number from 3,000 to 300, on the condition that it will submit additional clinical trial data.

The company said it could not achieve the goal because GIST was a rare disease. Also, the company obtained an indication for liver cancer in 2017, and a university hospital refused to participate in the PMS study citing risks of being involved in an illegal rebate issue, the company said.

Initially, the ministry’s panelists were skeptical about lowering the number of review cases for Bayer.

“The PMS period for patients with recently added indication was too short. I think it is not enough to complete the study with 300 cases by adding some to the currently registered 275 cases,” one member of the review panel said.

Another member said it seemed too late for Bayer to request the reduction because it submitted the request at the last stage of the reevaluation period. Initially, the company set the number at 3,000 for the PMS study.

A third committee member questioned if Bayer did its best to secure as many review cases as possible.

"I think it is unrealistic to set the target patient number at 3,000 for approval of a new drug, considering the number of patients and the timing of the insurance coverage,” a member said. “However, I doubt whether the company did its best to collect the cases. Even though I am a specialist treating GIST patients at a hospital, I did not receive any request from Bayer to participate in its PMS study.”

Another panelist said it was true that a university hospital would find it hard to participate in Bayer’s PMS study due to risks of being involved in an illegal rebate issue and the shortage of workforce.

A majority of the committee members were negative about lowering the number of review cases. However, they mostly agreed that the drug did not have a significant risk in safety.

The members of the central pharmaceutical affairs advisory committee decided to lower the number of review cases of Stivarga to 300.

If a new drug’s manufacturer under the reevaluation period does not meet the requirements, it faces sales suspension for three months in the first stage, six months in the second, and license cancellation in the last. The panelists made a quick decision apparently to prevent a drug supply panic.

“Considering the reality of conducting clinical trials, we order (Bayer) to collect at least 300 cases, as requested by the company. The company must submit all clinical trial data as of January 2019 by Aug. 21, 2019, the completion date of the reevaluation. It should include all patients enrolled by March 2019, considering the entire reporting period,” the chairman of the central pharmaceutical affairs advisory committee said.

At the meeting, an advisor said the government should revise requirements for drug reevaluation.

For reevaluation of a new drug, a company has to collect 3,000 cases if the drug is the world’s first medicine developed in Korea; if the drug is under development in foreign countries; if the new drug obtained approval overseas and three years have not passed since the approval date; or if the drug developed in a foreign country is not in use in any other country. Those other than the mentioned above should collect 600 cases.

The Korean system allows a company to set the number of PMS subjects if it submits objective and reasonable data for calculating the number. However, most of the time, pharmaceuticals do not submit such data and set the PMS study target at 3,000 or 600 cases.

If a PMS study aims to collect the early safety data of a new drug, it would be most desirable to obtain all the PMS cases, one of the committee members said.

“Considering the problem of the PMS system, the government should order companies to collect the safety data from all the patients to secure the adverse event examples in the early use of the drug. That way, we can collect real-world data including special side effects,” the committee member said. “There should be a rule for patients and doctors to participate in the PMS study mandatorily if they want to use a new drug.”

lhs@docdocdoc.co.kr

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