Five new drugs are planned to be breakthrough therapies from Junshi, Microchip, Novo Nordisk...

On March 16, the CDE official website announced that 4 new drugs will be included in the breakthrough therapy program.

Junshi Biologics' PD-1 Teriprizumab is used in the first-line treatment of mucosal melanoma;

Novo Nordisk's long-acting GLP-1 inhibitor Semaglutide (Semaglutide) is used in the treatment of NASH;

The first class of Microchip's new drug Cioroni is used in the treatment of ovarian cancer;

Yuheng Bio/WuXi Biologics PD-1 monoclonal antibody Sepalizumab (GLS-010) is used in the treatment of cervical cancer;

Shanghai Ruixing's oxynidone capsule is used for chronic hepatitis B fibrosis.

From the CDE official website

Teriprizumab, first-line treatment for mucosal melanoma

Just now, CDE announced that it intends to include teriprizumab as a breakthrough therapy.

In August 2019, the phase Ib clinical study data of teriprizumab combined with axitinib in the first-line treatment of advanced mucosal melanoma was published in the JCO journal.

Based on the breakthrough results of this research, the anti-PD-1 monoclonal antibody combined with axitinib for the treatment of mucosal melanoma obtained the "Chinese Society of Clinical Oncology (CSCO) Guidelines for Melanoma Diagnosis and Treatment" and "Chinese Society of Clinical Oncology (CSCO) Immunological Examinations" It is recommended by Level II experts in the "Recommended Guidelines for Clinical Application of Point Inhibitors".

Sioroni, the second breakthrough therapy designation

This time, the indications for Cioroni's breakthrough therapy are: combined with paclitaxel weekly therapy to treat platinum-refractory or platinum-resistant recurrent ovarian cancer.

From the CDE official website

Sioroni is a new chemical structure with global patent protection independently designed and developed by Microchip.

In previous clinical trials of Sioroni, compared with historical control data, for SCLC patients who failed multi-line therapy, his single-agent therapy achieved very positive results.

At present, according to the Insight database, Sioroni has carried out 7 clinical trials, 4 of which have been completed.

Theoroni has initiated a clinical trial (Insight)

The proposed breakthrough therapy this time is expected to accelerate the drug's listing process.

Semaglutide, type 2 diabetes has been reported for the market

This time, the indication for semaglutide's proposed breakthrough therapy is non-alcoholic fatty liver (NASH).

Semaglutide injection (Semaglutide, English trade name: Ozempic) is a long-acting GLP-1 receptor agonist developed by Novo Nordisk.

At present, 6 types of GLP-1 receptor agonists have been approved for marketing in China, which are imported exenatide (normal + long-acting), liraglutide, risnatide, and dulaglutide; domestically produced benaru Peptide, polyethylene glycol loxenatide.

On December 5, 2017, the FDA approved Ozempic (Semaglutide Injection) to aid diet control and exercise to improve blood sugar control in patients with type 2 diabetes.

In China, the marketing application for semaglutide injection was accepted by the CDE in April 2020, and it is expected to be approved in China in 2021.

PD-1 Sepalizumab, which has been reported for production in early 2020

Sepalizumab (GLS-010) was developed by WuXi Biologics under the entrustment of Yuheng Biotech.

The indications for the proposed breakthrough therapy this time are: recurrence or metastasis that has progressed after receiving first-line or above platinum-containing standard chemotherapy, and PD-L1 positive expression (CPS≥1) cervical cancer.

On February 18, 2020, the new drug application (NDA) for the treatment of relapsed or refractory classic Hodgkin's lymphoma (r/r cHL) above the second line has been accepted by the NMPA.

In the 2020 CSCO meeting, the Phase II clinical data of the drug for cervical cancer was disclosed.
As of April 2, 2020, a total of 45 patients have been included in the study and received treatment.
Forty-one evaluable patients underwent post-treatment tumor evaluation, 11 (26.
83%) patients achieved partial remission (PR), 11 (26.
83%) patients had stable disease (SD), and 19 (46.
34%) patients developed disease Progress (PD), ORR reached 26.
83%, DCR reached 53.
66%.

In terms of safety, as of April 2, 2020, among 45 patients, 36 patients (80%) had observed treatment-related adverse events (TRAE) of any grade, most of which were grade 1 or 2; the most common TRAE was anemia (26.
67%, 12/45); there were 17 patients (37.
78%) with TRAE ≥3.

Hydroxynidone capsules, chronic hepatitis B liver fibrosis

Hydroxynidone capsule (R&D code: F351) is a new chemical entity derived from Etuary® (pirfenidone) developed by GNI in Japan, which can inhibit the proliferation of hepatic stellate cells and the TGF-β signaling pathway.
Two pathways play a key role in visceral fibrosis.
F351 is mainly developed to treat liver fibrosis caused by alcohol, drugs, obesity or virus and kidney fibrosis caused by chronic kidney disease (especially diabetes).

The indication for this breakthrough therapy is chronic hepatitis B liver fibrosis.
Previously in August 2020, GNI Group released Phase II clinical data for this indication.

In this randomized, double-blind, placebo-controlled, multicenter, dose-escalation phase II clinical study, 168 patients were randomly divided into 4 dose-escalation groups: placebo, 60 mg/TID (3 times a day), 90 mg/TID, 120 mg/TID.
The main endpoint of the study is: according to the pathological analysis of liver biopsy, the liver fibrosis score (using the Ishak scoring system) before and after F351 treatment was reduced by one level.
Secondary endpoints include reduction in HBV DNA titer, reduction in liver fiber scan kpa score, reduction in liver inflammation score, and improvement in ALT levels.

The results showed that the study reached the primary endpoint: during the 52-week treatment period, the 90 mg/TID (270 mg/day) treatment group had the best improvement in Ishak scores compared to placebo.

In the study, F351 was generally well tolerated.
The incidence of adverse events of particular concern in patients in the placebo group, F351 60 mg/TID group, 90 mg/TID group, and 120 mg/TID group were: the incidence of skin events was 11.
63%, 4.
76%, 7.
14%, and 7.
32%, respectively The incidence of gastrointestinal events were 23.
26%, 21.
43%, 16.
67%, and 19.
51%; the incidence of serious adverse events were 4.
65%, 2.
38%, 2.
38%, and 7.
32%, respectively.