Central Committee conflicted over Rekirona limits use

Some opposed of conditional approval, “Need to revisit after Phase III”

Celltrion “Meaningful to have shortened the time to recovery in mild condition patients”

Apparently, the Central Pharmaceutical Affairs Deliberation Committee has reached a conclusion after an intense discussion in approving of Celltrion’s COVID-19 monoclonal antibody treatment Rekirona, conditionally authorized for use on Feb.

 

5.

 

The Central Pharmaceutical Affairs Deliberation Committee was convened for a meeting on Jan.

 

27 and advised Rekirona to be conditionally used on high-risk patients with mild COVID-19 symptoms and patients with moderate symptoms.

 

The indication was actually narrowed from the COVID-19 Treatment Advisory Panel’s previously opinion that the treatment can be used without a limitation in patients with mild to moderate symptoms.

 

In the Central Committee meeting minute disclosed on Feb.

 

18, many have raised concerns of using the drug for patients with mild symptoms and the opinions were vastly split.

 

Total 18 of experts and five Ministry of Food and Drug Safety (MFDS) officials participated in the meeting held on the day.

 

A committee member proposed a conditional approval, as “the clinical recovery as of Feb.

 

14 confirmed the meaningful efficacy.

 

The applicant targets patients with mild to moderate symptom, but the submitted evidence showed statistical improvement of the symptoms only in patients with moderate symptoms (40 mg/ kg) among overall patients with mild and moderate symptoms and age 50 and over patients with moderate level of symptoms.” Another committee member recommended, “As an advisor, I can see the data confirming the improvement in patients with mild symptoms, but considering it would be an expensive drug, shortening the time to recover by a few days in the mild condition patient would not be meaningful, clinically speaking.” However, Celltrion refuted shortening the time to recover in mild condition patient is a meaningful outcome.

 

The company official was connected via video conference call during the meeting and said, “As far as the symptom improvement goes, the efficacy in patients with mild symptoms is comparatively lower than in patients with moderate symptoms, but still the time to recover was reduced.

 

It would be beneficial to the patients with mild condition to lessen the number of recovery days, too.” The official also told the company aims to complete registering 1,172 participating COVID-19 patients in April through May for the Phase III clinical trial.

 

Some also urged the agenda should be revisited when more data is collected from the Phase III trial.

 

A committee member advised, “Rather, it would be more appropriate to grant a limited approval for patients with underlying condition of pneumonia, who could develop the symptoms worse.

 

The definite decision should be made after re-discussing about the drug, when it comes back with sufficient Phase III trial data.” Rekirona injection, in fact, has caused a conflict already, when the company presented the Phase II trial outcome.

 

Among the primary efficacy endpoints, the drug demonstrated statistically meaningful improvement in clinical recovery only, while the drug did not achieve another satisfactory endpoint, the virus shedding time.

 

A MFDS official participating at the meeting commented, “Some Phase III trials designed with multiple primary endpoints confirm the efficacy when two endpoints are achieved.

 

But this Phase II trial was not designed as a multiple testing.” “Comparing the two endpoints, the clinical recovery seems to be more valuable endpoint, which was met.

 

The virus shedding endpoint was not met as expected, but the drug could have shown the mechanism of shedding the virus as patients’ level of virus demonstrated the descending tendency with the drug administration,” the official added.

 

However, some even urged they can hardly support the idea of conditional approval as the secondary endpoints, such as hospitalization, oxygen therapy, and decrease in death rate, were not able to verify properly, let alone the primary endpoints.

 

One of the members also noted, “The current data is only sufficient for an emergency use authorization than a conditional approval,” and some others agreed.

 

Rekirona injection earned the authorization on Feb.

 

5 with a condition to provide Phase III clinical trial data.

 

In accordance to the Central Committee’s recommendation, the drug is indicated to be used on high-risk COVID-19 patients with mild symptoms, or patients with moderate symptoms (age over 18) to improve their clinical symptoms.

 

The high-risk patients with mild symptoms are limited to patients aged over 60 or having one of underlying conditions (cardiovascular disease, chronic respiratory disease, diabetes or hypertension).

 

On Feb.

 

17, Rekirona injection started supplying to healthcare institutes in South Korea.