**: Pharmaceutical Intelligence Headlines***
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In 2023, the FDA approved a total of 15 innovative oncology drugs, including 4 new bispecific antibody drugs, 5 monoclonal antibody and peptide drugs, and 6 small molecule drugs. A number of novel targets and novel mechanisms have been approved for marketing, such as the first AKT inhibitor, the first oral SERD inhibitor and the first reversible BTK inhibitor.
Among them, a number of domestic innovative oncology drugs have successfully landed in the US market, such as Chi-Med's fruquintinib, Junshi Biosciences' toripalimab, and Yifan Pharma's ibergostim injection, marking the steady improvement of the strength of domestic innovative drugs to go overseas.
Table: Innovative anti-tumor drugs approved by the FDA for marketing in 2023
Data**: Collation of pharmaceutical intelligence data and public information.
Bispecific antibodies
2023 can be described as a big year for bispecific antibodies, with the FDA approving a total of 4 bispecific antibody drugs, including CD3 CD20 bispecific antibodies Epcoritamab and Glofitamab, CD3 GPRC5D bispecific antibody talquetamab and CD3 BCMA bispecific antibody elranatamab.
1) Epcoritamab (epkinly) is a CD3 CD20 bispecific antibody under AbbVie, which was approved by the FDA in May 2023 for the treatment of diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic** or refractory (R R). Epcoritamab-BYSP binds both CD3 on T cells and CD20 on B cells and induces T cell-mediated CD20+ cell killing.
The launch of epcoritamab is based on the results of the Phase I II EPCore NHL-1 trial. The trial results showed an objective response rate (ORR) of 61 percent, a complete response rate (CR) of 38 percent, and a partial response rate (PR) of 23 percent in all DLBCL patients receiving epcoritamab**. The median duration of response (DOR) was 15The 6-month, 9-month DOR rate was 63%.
2) Glofitamab is a novel LGG1-like humanized CD20xCD3 bispecific antibody from Roche, which was approved by the FDA for marketing on June 15, 2023, for adult patients with refractory (R R) non-specified diffuse large B-cell lymphoma (DLBCL, NOS) or follicular lymphoma caused by **2 or more lines of systemic **.
The U.S. FDA's approval of Glofitamab is based on positive results from the Phase I II NP30179 study. The results showed durable response in DLBCL patients receiving grofituzumab**, with an overall response rate (ORR) of 56% (74 132) and a complete response rate (CR) of 43%. In addition, more than 2 in 3 people who responded to ** showed remission that lasted at least 9 months. The median duration of response (MDOR) was 184 months.
3) Talquetamab is a CD3 GPRC5D bispecific antibody of Janssen Company, which was approved by the FDA for marketing in August 2023 for the indication of adult patients with or refractory multiple myeloma who have received at least four prior treatments.
The launch of talquetamab is based on the results of the Phase II Monumental-1 study. The trial included 187 patients who had received at least 4 prior lines** and had not previously received T-cell redirection**. When the frequency of administration is 0At 8 mg kg, 73Six percent of patients achieved ORR, 58 percent achieved a very good partial response (VGPR) or above, and about 30 percent achieved a complete response (CR) or better.
4) Elranatama, a CD3 BCMA bispecific antibody from Pfizer, was approved by the FDA in August 2023 for patients with refractory multiple myeloma (R r mm) who have received at least four prior lines of treatment, including proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies.
Elranatamab was approved based on data from a Phase 2 trial called MagnetisMM-3. The study included a total of 187 patients with multiple myeloma who were resistant to at least one PI, one IMID, and one anti-CD38 monoclonal antibody. A total of 123 patients in key cohort A have not received BCMA-directed **, and the overall response rate (ORR) is as high as 577%, with a complete response rate of 258%；Cohort B consisted of 64 patients who had previously received BCMA-targeted antibody drug conjugates or CAR-T cells** and had an overall response rate (ORR) of 333%, and the 9-month DOR rate was 843%。
Monoclonal antibodies and peptide drugs
In 2023, the FDA will approve a total of five monoclonal antibody and peptide drugs for marketing, two of which are domestic drugs, including Toripalimab from Junshi Biosciences and Ibergostim Injection from Yifan Pharmaceutical.
1) Toripalimab is a PD-1 monoclonal antibody under Junshi Biosciences, which was approved by the FDA on October 29, 2023 for first-line nasopharyngeal carcinoma and ** disease-progressing, unresectable or metastatic nasopharyngeal carcinoma that has progressed during or after previous platinum-containing disease.
On February 2, 2021, Junshi Biosciences signed a licensing and commercialization agreement with Coherus. Under the terms of the agreement, Junshi Biosciences will license Coherus toripalimab and two optional programs for up to a total of up to 11$100 million down payment, optional project execution fees, and milestone payments. One of the down payments is 1US$500 million, after reaching the corresponding milestone event, Junshi Biosciences will receive no more than 3$800 million milestone plus a 20% share of toripalimab's annual net sales revenue in the licensed territory.
2) Retifanlimab is a PD-1 monoclonal antibody under Incyte, which was approved by the FDA in March 2023 for the treatment of patients with **metastatic or **locally advanced Merkel cell carcinoma (MCC)**.
The approval of retifanlimab was based on data from an open-label, single-arm Phase II clinical study (POD1UM-201).
The results showed an objective response rate (ORR) of 52% for retifanlimab monotherapy in patients who had not received prior chemotherapy (n=65). Of these, 12 patients (18%) achieved a complete response and 22 patients (34%) achieved a partial response. In patients who achieved remission, the duration of response (DOR) was 11-24.9 months. Seventy-six percent (26 to 34) had a dorm of more than 6 months, and 62% (21 to 34) had a dorm of more than 12 months.
3) Ibergostim Injection (F-627) is the third-generation long-acting whitening drug of Yiyi Biologics, a subsidiary of Yifan Pharmaceutical, and the world's first bimolecular G-CSF-FC fusion protein, which has the significant advantages of high stability and low immunogenicity. In November 2023, ibersomistim injection was approved by the FDA for the treatment of adult patients with non-myeloid malignant tumors to reduce the incidence of infection manifested by febrile agranulocytopenia when receiving myelosuppressive anticancer drugs** that are prone to cause febrile agranulocytopenia.
4) Motixafortide is a synthetic cyclic peptide of Biolinerx, targeting CXCR4, which was approved by the FDA for marketing in September 2023 for the indication of mobilizing hematopoietic stem cells into peripheral blood in combination with Filgrastim (granulocyte colony-stimulating factor G-CSF) as a stem cell mobilization (SCM) to promote autologous transplantation in patients with multiple myeloma at the time of transplantation. Aphexda, which is administered by subcutaneous injection, is the first innovative drug in a decade to receive FDA approval for multiple myeloma stem cell mobilization.
The launch of Motixafortide is based on the results of a two-part Phase Trial of Genesis, a randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of Motixafortide plus G-CSF versus placebo plus G-CSF to mobilize hematopoietic stem cells for autologous transplantation in patients with multiple myeloma. According to laboratory measurements, the Motixafortide plus G-CSF combination regimen resulted in 675% of patients achieved their goal of 6 million CD34-positive cells per kilogram of stem cells in two apheresis** sessions, compared to 9 in the placebo plus G-CSF group5%。
5) Flotufolastat F18 is an optimized PSMA-targeting molecule that binds to and is internalized by PSMA-expressing cells, including prostate cancer cells that are typically overexpressed PSMA. It is labeled as the radioisotope fluorine-18 (18F) in order to perform PET imaging of the prostate and other areas of the body where prostate cancer may have spread. Flotufolastat F 18 was approved by the FDA in May 2023 and is the first and only PSMA-targeted imaging agent to be approved by the U.S. Food and Drug Administration.
Small molecule drugs
In 2023, the FDA approved a total of 6 small molecule drugs for marketing, including the first oral SERD inhibitor elastrant, the first non-covalent reversible BTK inhibitor pitobrutinib, and the first AKT inhibitor capivasertib. Chi-Med's fruquintinib was approved by the FDA in November, marking a milestone for a Chinese small molecule drug to go global.
1) Fruquintinib, a highly selective and potent inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2 and -3 of Chi-Med, was approved by the FDA in November 2023 for the treatment of prior fluorouracil, oxaliplatin and irinotecan-based chemotherapy and anti-vascular endothelial growth factor (EGF)."vegf"and patients with metastatic colorectal cancer who are anti-epidermal growth factor receptor (EGFR).
In January 2023, HUTCHMED entered into a partnership with Takeda, whereby Takeda made an upfront payment of US$400 million and up to US$7.02 to HUTCHMEDThe US$300 million potential milestone fee will be awarded to fruquintinib, making it one of the largest down payments in a domestic innovative drug licensing transaction to an overseas pharmaceutical company. Fruquintinib's FDA approval triggers a $35 million milestone payment.
2) Elacestrant is the world's first approved oral SERD inhibitor, which was approved by the FDA in January 2023 for the indication of postmenopausal women or adult men with advanced or metastatic breast cancer who have received at least one line of endocrine** disease progression after disease progression.
In a phase III clinical trial called emerald, elastrant included 478 female and male patients with ER+, HER2- advanced or metastatic postmenopausal disease, including 228 patients with ESR1 mutations. Median PFS was 3 in the Elacestrant group and fulvestrant or aromatase inhibitor groups, respectively8 months and 19 months (hr=0.)55, p-value = 00005)。Elastran defeated fulvestrant head-to-head.
The approval of alasterant will fill the current vacancy in the posterior line of ER+ HER2- and ESR1-mutated advanced breast cancer, and also provide a safe and effective way for patients resistant to CDK4 6 inhibitors, further enriching the diagnosis and treatment pattern of endocrine-resistant breast cancer patients.
On November 7, 2023, SciClone Pharmaceuticals and Menarini Group entered into an exclusive license and cooperation agreement for the development and commercialization of iralastran in China.
3) Pirtobrutinib (LOXO-305) is a new generation of BTK inhibitors under Eli Lilly, which is the first and only non-covalent reversible BTK inhibitor approved by the FDA, which can solve the problem of drug resistance of the first generation of irreversible BTK inhibitors. Pitobrutinib was approved for two indications in 2023, first in patients with refractory MCL** who have received at least second-line system** (including BTK inhibitors) prior on January 27, 2023. It was later approved on December 1, 2023 for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL SLL)** who have received at least two prior lines**, including BTK inhibitors and BCL-2 inhibitors.
The launch of pitobrutinib was based on a phase trial called Bruin, which showed an overall response rate of 79% and a median progression-free survival of 16 in 100 patients with CLL SLL who had previously received BTK and BCL-2At 8 months, there was a good response to patients with CLL SLL who were resistant to BTK and BCL-2 inhibitors.
4) Quizartinib is a potent and selective second-generation type 2 FLT3 inhibitor that was approved by the FDA on July 20, 2023 for the first-line** and adjuvant diagnosis of rare FLT3-ITD-positive acute myeloid leukemia (AML), which is one of the most common genetic mutations in AML patients and is associated with a high risk of AML** and a poor prognosis, approximately 30% of treatment-naïve AML patients develop FLT3 mutations.
The launch of quezatinib was based on a Phase 3 study called Quantum-First, in which 539 patients with newly diagnosed FLT3-ITD-positive AML were randomized (1:1) to receive quizartinib (n=268) or placebo (n=271) in combination with standard induction and consolidation**, followed by continued single-agent maintenance**. The results showed a statistically significant improvement in overall survival (OS) with a MOS of 31 in patients who received quizartinib in combination with standard induction and consolidation chemotherapy** and then continued to receive quizartinib alone** compared to the placebo group9m and 151m (hr is 0.)78）。But quizartinib has a black box warning of torsade de pointes and cardiac arrest.
5) Repotrectinib is a next-generation kinase inhibitor targeting ROS1 and NTRK oncogenic factors jointly developed by BMS and Zai Lab, which was approved by the FDA in November 2023 for patients with RoS1-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).
The launch of repretinib was based on the results of the Phase I and II Trident-1 trial, which showed that repretinib had an objective response rate (ORR) of 79%, including a complete response rate (CR) of 6% and a partial response rate (PR) of 73% in ROS1-TKI-naïve patients (N=71). In patients (n=56) who had received one prior ROS1-TKI and had not received chemotherapy, the ORR was 38 percent, the CR was 5 percent, and the PR was 32 percent.
In July 2020, Zai Lab entered into a partnership with Turning Point to acquire exclusive rights to develop and commercialize repretinib in Greater China, including Chinese mainland, Hong Kong, Macau and Taiwan. On June 28, 2023, Zai Lab announced that the National Medical Products Administration (NMPA) has accepted an NDA for repotrectinib in patients with Ro1-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).
6) Capivasertib is an AKT inhibitor under AstraZeneca, which was approved by the FDA for marketing in November 2023 for the indication of adult patients with advanced or metastatic breast cancer who are hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative in combination with fulvestrant (fulvestrant). Capivasertib is the world's first marketed AKT inhibitor.
The marketing of capivasertib is based on a phase III study called Capitello-291 in which 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer were randomized (1:1) to receive either capivasertib 400 mg or placebo orally administered 500 mg intramuscularly on days 1 and 15 of cycle 1 and every 28 days thereafter. The results showed a median PFS of 7 in the Capivasertib-fulvestib groupAt 3 months, the placebo-fulvest group was 31 month (hr=0.)50, p-value < 00001)。
Source**: FDA website.
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