FDA raises standards Agenus withdraws PD-1 listing application

On October 22, Agenus announced the withdrawal of its PD-1 monoclonal antibody balstilimab single-drug application for recurrent or metastatic cervical cancer patients who have progressed after chemotherapy
.
The application was accepted by the FDA on June 17, 2021 and was also eligible for priority review.

Agenus conducted the largest single-arm study to date in patients with cervical cancer who recurred or metastasized after chemotherapy.
Among 140 patients with evaluable efficacy, the ORR of balstilimab for PD-L1 positive and negative patients was 20.
% And 8%
.
In contrast, the ORR of Keytruda single agent for these two groups of people was 14.

Although 3 on-site inspections have been completed on the marketing application of balstilimab and no problems have been pointed out (Form 483s is issued), the FDA still believes that it is no longer suitable for accelerated approval of the same indication for balstilimab based on the results of a single-arm study.
And recommended that Agenus withdraw the listing application
.
Because Keytruda is also a single-agent second-line treatment for cervical cancer, the indications have just been transferred to full approval

On October 13, the FDA not only approved pembrolizumab + chemotherapy ± bevacizumab for the first-line treatment of PD-L1 (comprehensive positive score [CPS]≥1) based on the results of the confirmatory phase III KEYNOTE-826 study.
For patients with persistent, recurrent or metastatic cervical cancer, at the same time, the indications of Keytruda as a single-agent second-line treatment of cervical cancer were transferred to full approval
.

According to Endpoints, Agenus had already protested with the FDA before officially announcing the withdrawal of the listing application, including writing to Richard Pazdur, director of the FDA's Cancer Review Center
.
Agenus believes that the FDA is biased towards Merck, and its CEO Garo Armen even claimed that Merck did not submit any additional clinical data to the FDA for the indication of Keytruda's second-line treatment for cervical cancer.

Armen said: "There is no law expressly stipulating that the FDA cannot do this, but for a second-line indication, it is unusual for the FDA to make a decision 4 months in advance without additional supplementary data as a basis.
"
.
According to the information disclosed by Armen, the FDA insists that the efficacy data of balstilimab cannot prove to be better than existing therapies and does not meet the conditions for accelerated approval

With the withdrawal of the listing application, Agenus will also terminate its ongoing confirmatory clinical trial code-named BRAVA, which is expected to save Agenus US$100 million in research and development expenditures
.
However, in view of the benefits observed in clinical trials, Agenus plans to launch an "improved access" project in multiple countries so that patients and doctors can use balstilimab

The development rights of balstilimab in China belong to Betta Pharmaceuticals
.
On June 22, 2020, Betta Pharmaceuticals and Agenus reached a partnership to pay Agenus US$15 million as a down payment, and at the same time subscribe for Agenus’s additional shares with US$20 million in cash, to obtain balstilimab and zalifrelimab (CTLA-4 antibody) in China (Including Hong Kong, Macau and Taiwan) Exclusive development and commercialization rights for single use or in combination with other drugs for the treatment of indications other than bladder cancer

So far, Pembrolizumab is the only PD-1 antibody approved for the treatment of cervical cancer indications, covering second-line and first-line drugs
.
However, the development competition for cervical cancer is also escalating