Breakthrough treatment varieties refer to innovative drugs or improved new drugs used to prevent and treat diseases that seriously endanger life or seriously affect quality of life, and for which there are no effective prevention and treatment methods or sufficient evidence to show significant clinical advantages compared to existing treatment methods. After obtaining this recognition, it can accelerate the review process, accelerate the drug development process, and solve the unmet clinical needs of patients.

In the past October, the CDE official website plans to include 5 breakthrough therapy varieties, including 1 therapeutic vaccine, 3 ADC drugs, and 1 monoclonal antibody drug. The following are introductions to 5 innovative drugs for reference only.

1. TVAX-008: Hepatitis B
On October 14th, Nanjing Yuanda Weixin Biopharmaceutical Co., Ltd. TVAX-008 applied to be included in the breakthrough treatment category, suitable for the treatment of chronic hepatitis B virus (HBV) infection.
TVAX-008 is a therapeutic hepatitis B vaccine under research independently developed by Nanjing Yuansai Weixin Biomedical Co., Ltd. TVAX-008 utilizes multi-target HBsAg and HBcAg combined with CpG adjuvant, where HBsAg/HBcAg promotes humoral immunity and restores Th1/Th2 balance; CpG activates TLR9 of B cells and pDC to induce cellular immunity against hepatitis B virus. TVAX-008 presents hepatitis B antigen through different ways, breaks through the body's immune tolerance, effectively induces the body's immune response, and then makes it possible to cure HBV clinically.
The preclinical animal model data previously published in the Vaccine journal showed that TVAX-008 injection did not have any effects on transgenic mice, such as tissue organs and body weight indicators, and there was no mouse death, indicating overall high safety. TVAX-008 can induce strong humoral and cellular immune responses in C57BL/6 mice; In different serotypes of HBV transgenic mice and immune tolerant mice, they can also produce strong humoral and cellular immune responses, and break through immune tolerance. The clearance rate of hepatitis B surface antigen (HBsAg) level reaches more than 98%.
In addition, completed Phase I clinical studies have shown good efficacy and safety data for TVAX-008. According to the official website of the China Drug Clinical Trial Registration and Information Disclosure Platform, TVAX-008 has entered the phase II clinical trial stage; This trial is a multicenter, randomized, double-blind, placebo-controlled phase II clinical study aimed at evaluating the therapeutic efficacy and safety of TVAX-008 injection in patients with chronic hepatitis B after treatment, with the main efficacy endpoint being the HBsAg seroconversion rate at week 73.

2. HMI-115: Moderate to severe pain in endometriosis
On October 15th, HMI-115 from Qirui Pharmaceutical (Nanjing) Co., Ltd. applied for inclusion in a breakthrough treatment variety, suitable for treating moderate to severe pain related to endometriosis.
HMI-115 is a monoclonal antibody targeting the prolactin receptor (PRLR), developed for the treatment of endometriosis and androgenic alopecia. It has demonstrated excellent properties in animal models, including non-human primate (NHP) models, and in terms of human safety. The drug was initially developed by Bayer as a treatment for endometriosis. In April 2019, Sinopharm and Bayer signed a global exclusive licensing agreement, obtaining the authorization to develop and industrialize HMI-115 for multiple indications worldwide.
In October 2024, Heqirui Pharmaceutical announced the positive results of a mid-term analysis of a phase 2 study conducted on HMI-115 in female patients with moderate to severe endometriosis related pain. This Phase 2 study is an international multicenter, randomized, double-blind, placebo-controlled trial used to evaluate the safety and efficacy of HMI-115 in women with moderate to severe endometriosis related pain during a 12 week treatment period. The study was conducted among 142 female patients including those from the United States, Poland, and China. The mid-term study showed that compared to baseline, the average dysmenorrhea pain score in the 240 mg q2w group decreased by 42%; The average non menstrual pelvic pain score decreased by 50%; Most patients report normal menstruation; No typical symptoms of perimenopause were reported; There were no significant changes in bone mineral density and sex hormone levels (including estradiol, LH, FSH, and progesterone).

3. HS-20093: Widespread small cell lung cancer
On October 24th, Shanghai Hanson Biopharmaceutical Technology Co., Ltd. applied to include HS-20093 for injection as a breakthrough treatment for extensive stage small cell lung cancer after standard first-line treatment (including platinum dual drug chemotherapy combined with immunotherapy). It is worth noting that HS-20093 also obtained breakthrough therapy (BTD) certification from the US FDA before being included in the CDE breakthrough therapy variety this time.
HS-20093 is a novel antibody conjugated drug (ADC) developed by Hanson Pharmaceuticals targeting B7-H3. It consists of a fully humanized anti-B7-H3 monoclonal antibody and a topoisomerase I inhibitor, linked by a cleavable maleimide tetrapeptide chain. Public information shows that HS-20093 has over ten clinical studies underway, including two phase III clinical studies targeting recurrent small cell lung cancer and localized small cell lung cancer, as well as multiple phase I and II clinical studies for the treatment of lung cancer, sarcoma, head and neck cancer, and other solid tumors.
In a multicenter, open label Phase I ARTEMIS-001 clinical trial, the safety and efficacy of HS-20093 in the treatment of advanced solid tumor patients (including small cell lung cancer) were evaluated. The research results showed that the ORR of the 8.0mg/kg dose group was 61.3%, DCR was 80.6%, median DOR was 6.4 months, median PFS was 5.9 months, and median OS was 9.8 months; The ORR of the 10.0mg/kg dose group was 50.0%, DCR was 95.5%, median DOR was 8.9 months, median PFS was 7.3 months, and median OS had not yet been reached; Among patients who have previously received IO+platinum based drugs but have not received TOPO1i treatment, the ORR of the 8.0 and 10.0mg/kg dose groups were 75.0% and 66.7%, respectively; There is no significant correlation between the expression level of B7-H3 and ORR; However, patients with positive expression of B7-H3 immunohistochemistry (IHC) (≥ 1%) showed a trend towards prolonged median progression free survival (PFS). In terms of security, its security features are consistent with previous reports.
In December 2023, Hanson Pharmaceuticals entered into an exclusive licensing agreement with GlaxoSmithKline (GSK) worth over $1.7 billion, granting GSK a global exclusive license to develop, produce, and commercialize HS-20093 (excluding Greater China). In August of this year, GSK announced that HS-20093 had received breakthrough therapy recognition from the FDA for the treatment of recurrent or refractory ES-SCLC patients who progressed during or after platinum based chemotherapy.

4. YL201: Recurrent small cell lung cancer
On October 24th, Suzhou Yilian Biopharmaceutical Co., Ltd. applied for inclusion of YL201 for injection as a breakthrough treatment variety, suitable for the treatment of recurrent small cell lung cancer that had failed initial platinum therapy.
YL201 is an antibody conjugated drug (ADC) developed by Yilian Biotech that targets B7-H3. The B7-H3 target is highly expressed in esophageal cancer, and combined with the tumor microenvironment and traditional lysosomal extracellular and intracellular dual lysis mechanism of the TMALAN technology platform of Yilian Biotech, it can effectively kill tumor cells.
In September 2024, Yilian Biotechnology announced that the clinical data of YL201 would be presented orally at the European Society of Oncology (ESMO) in 2024. As of August 9, 2024, the Phase 1 study included a total of 312 patients with advanced solid tumors, including extensive stage small cell lung cancer (ES-SCLC), nasopharyngeal cancer, and driver gene negative non-small cell lung cancer. In terms of effectiveness, as of August 9, 2024, among 276 patients who underwent at least one baseline tumor assessment, the objective response rate (ORR) was 44.6% and the disease control rate (DCR) was 83.7%. Among them, there are a total of 72 patients in the ES-SCLC cohort who can be evaluated for efficacy. All of them have received platinum based chemotherapy in the past, and 95% have received anti-PD-1/L1 treatment. The ORR of YL201 in ES-SCLC patients is 68.1% (≥ 2.0mg/kg ORR is 70.0%), and the mPFS is 6.2 months (≥ 2.0mg/kg mPFS is 6.2 months). It is worth mentioning that the efficacy of YL201 in patients with brain metastases is comparable to the overall population, with an ORR of 52.2% and an mPFS of 5.3 months. YL201 has shown significant improvement compared to existing standard treatments, while also having good safety and tolerability.

5. Trop2 monoclonal antibody SN38 conjugate: triple negative breast cancer
On October 25, Shanghai Shijian Biotechnology Co., Ltd. and Dongyao Pharmaceutical Co., Ltd. applied to incorporate the humanized anti-Trop2 monoclonal antibody SN38 conjugate into the breakthrough treatment category, which is applicable to inoperable local advanced, recurrent or metastatic PD-L1 negative triple negative breast cancer without systematic treatment in the past.
This innovative ADC drug was developed by Shijian Biotechnology. Its structural feature is the coupling of topoisomerase I inhibitor SN-38 with human Trop2 IgG1 monoclonal antibody through a stable cleavable linker, resulting in a drug to antibody ratio (DAR) of 8. Clinical trial data shows that the tolerated dose of ESG401 is significantly higher than other ADC drugs with similar targets. Its incidence of off target and on target toxicity is low and mild, demonstrating significant safety advantages. At present, ESG401 has entered the key registered phase 3 clinical trial stage for the indication of "HR+/HER2 metastatic breast cancer that has received at least first-line systematic chemotherapy in the past".
In a phase 1b study of a first-line treatment cohort of metastatic triple negative breast cancer (mTNBC), 28 patients with metastatic triple negative breast cancer who received first-line treatment received ESG401 at least once, and the longest treatment time reached 12.5 months. Among the 22 patients with assessable efficacy, the objective remission rate reached 86%, including 1 patient achieving complete remission, and the disease control rate reached 100%. A phase Ia dose escalation study published in Cell Reports Medicine showed that in patients with advanced metastatic solid tumors, the objective response rate (ORR) was 34.2%, the clinical benefit rate (CBR) was 50.0%, the disease control rate (DCR) was 65.8%, the median progression free survival (PFS) was 5.1 months, and the median duration of response (DOR) was 6.3 months. Among HR+/HER2 breast cancer patients who received treatment related dose (TRD) and whose efficacy could be evaluated, ORR was 47.0% and DCR was 70.6%. In patients with advanced triple negative breast cancer, ORR was 29.4% and DCR was 52.9%.

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