Avutometinib/Defactinib

In May 2025, the global pharmaceutical landscape witnessed a wave of innovation. From treating rare diseases such as KRAS‑mutant low‑grade serous ovarian cancer, pheochromocytoma, and paraganglioma to addressing widespread public health conditions like chronic obstructive pulmonary disease (COPD), postoperative pain, and influenza A virus infection, this series of drug approvals not only highlights the tireless efforts of medical researchers to overcome challenging diseases, but also reflects pharmaceutical companies’ ongoing commitment to advancing personalized and precision medicine. Notably, many of this month’s approved drugs are based on cutting‑edge biotechnologies and molecularly targeted therapies, offering new hope for patients with resistant or hard‑to‑treat conditions. 1. Avutometinib/Defactinib Avutometinib/Defactinib (AVMAPKI FAKZYNJA CO-PACK), developed by Verastem, is a combination of small-molecule drugs approved in the United States on May 8, 2025 for the treatment of KRAS‑mutant low‑grade serous ovarian cancer. Avutometinib is a RAF/MEK inhibitor that blocks the RAS‑RAF‑MEK‑ERK signaling pathway. It selectively inhibits MEK kinase activity, preventing downstream ERK activation and suppressing tumor cell proliferation and survival—a critical action in tumors harboring KRAS mutations that drive pathway hyperactivation. Defactinib is a focal adhesion kinase (FAK) inhibitor that disrupts tumor–stroma interactions, thereby reducing cancer cell migration, invasion, and metastatic potential. FAK is essential for cytoskeletal remodeling, adhesion, and motility; its overexpression is associated with numerous cancers. The combination yields synergistic effects: juntos they inhibit cell proliferation and prevent metastasis, offering a comprehensive therapeutic option for KRAS-mutant low-grade serous ovarian cancer. Clinical data demonstrate significant tumor growth inhibition and extended progression-free survival, improved patient quality of life, and a favorable safety and drug interaction profile. Verastem employed advanced formulation and pharmacokinetic design to ensure stability and bioavailability, showing comparable or superior efficacy compared with single agents. Post-approval, the company plans further pharmacovigilance, Phase IV trials to optimize dosing, expand indications, and evaluate long-term outcomes. Among current targeted therapies, several RAF/MEK and FAK inhibitors exist—Amgen’s Lumakras (sotorasib) and Mirati’s Adagrasib target KRAS G12C mutation directly—yet are mutation-specific. In contrast, Avutometinib/Defactinib offers broad-spectrum pathway inhibition, addressing complex KRAS-mutant cases. AstraZeneca’s Selumetinib (a MEK inhibitor) is another competitor, used in certain neurofibromatosis subtypes. 2. Velaglucerase Beta Velaglucerase beta (CAN‑103), developed by CANbridge Life Sciences, received approval in China on May 13, 2025 for the treatment of Gaucher disease types I and III. It is a humanized recombinant β‑glucocerebrosidase enzyme replacement therapy. Gaucher disease, caused by GBA gene mutations, results in deficient glucocerebrosidase activity, leading to intracellular lipid accumulation—especially in macrophages (so-called Gaucher cells)—and manifestations such as hepatosplenomegaly, bone disease, and systemic involvement. Velaglucerase beta provides functional enzyme to degrade stored glucocerebroside into glucose and ceramide, preventing lipid accumulation, restoring metabolic balance, and improving clinical outcomes. This enzyme demonstrates high stability and bioavailability, rapidly distributing to target tissues post-infusion and sustaining therapeutic effect. Clinical trials confirmed it significantly reduced liver and spleen volume, alleviated bone pain, increased hemoglobin, improved platelet counts, and enhanced quality of life—without serious adverse events. CANbridge utilized advanced bioprocessing and pharmacokinetic optimization to achieve equivalent or superior efficacy compared to existing enzyme replacement therapies. Following market approval, CANbridge will continue pharmacovigilance and Phase IV studies to expand indications and assess long-term efficacy. Existing Gaucher enzyme therapies include Sanofi’s Cerezyme and Pfizer’s Vpriv, both delivering exogenous enzyme effective for symptom improvement but subject to immune reaction-related variability. Velaglucerase beta, as a new humanized recombinant enzyme, offers improved affinity, lower immunogenicity, and high purity and stability—making it a favorable alternative in enzyme replacement therapy. 3. Anrikefon Anrikefon (HSK-21542), developed by Haisco Pharmaceutical Co., Ltd., was approved in China on May 13, 2025, for the treatment of postoperative pain. Anrikefon is a selective κ-opioid receptor agonist that exerts analgesic effects primarily by specifically binding to and activating κ-opioid receptors in the central and peripheral nervous systems. Compared to traditional μ-opioid receptor agonists, κ-opioid receptor agonists offer lower risks of addiction and respiratory depression while effectively relieving pain. By activating downstream signaling pathways through κ-receptor binding, Anrikefon suppresses nociceptive neuron activity and reduces the transmission of pain signals. Additionally, κ-opioid receptors play a role in emotional and stress regulation, making Anrikefon not only effective in relieving acute pain but also beneficial in improving mood and alleviating anxiety and depressive symptoms. Studies have shown that Anrikefon has high affinity and selectivity in vivo, delivering significant analgesic effects at lower doses and avoiding common side effects of traditional opioids, such as constipation, nausea, and vomiting. This unique mechanism of action positions Anrikefon as a highly promising novel analgesic. Clinical data demonstrate that Anrikefon provides excellent postoperative pain relief, significantly lowering pain scores and reducing the need for additional analgesics without causing severe adverse events or drug interactions. Currently, the postoperative pain management market includes widely used analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and traditional opioids like morphine and oxycodone. While these drugs are effective in pain relief, they often come with adverse effects such as addiction, respiratory depression, and gastrointestinal disturbances. In contrast, Anrikefon, as a selective κ-opioid receptor agonist, provides superior safety and tolerability, reducing the risk of adverse effects while maintaining effective analgesia. Other competing products include Pfizer’s Remoxy (an extended-release opioid) and Egalet’s Arymo ER (an abuse-deterrent formulation of morphine), both designed to minimize misuse and side effects through enhanced drug delivery technologies. 4. Birociclib Birociclib, developed by Xuanzhu Pharmaceutical Technology Co., Ltd., was approved in China on May 13, 2025, for the treatment of HR-positive/HER2-negative breast cancer. Birociclib is a selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. It works by specifically inhibiting the CDK4/6–cyclin D complex, thereby preventing phosphorylation of the retinoblastoma (Rb) protein. When Rb is unphosphorylated, it halts cell cycle progression from the G1 to S phase, effectively suppressing tumor cell proliferation. In HR-positive/HER2-negative breast cancer, the estrogen receptor (ER) signaling pathway is frequently activated, leading to increased cyclin D expression and promoting Rb phosphorylation via CDK4/6. Birociclib blocks this pathway, thereby halting tumor cell growth and division. Moreover, CDK4/6 inhibitors have also been shown to enhance immune system recognition and elimination of tumor cells, potentially producing synergistic effects when used with immunotherapies. Studies demonstrate that Birociclib has high selectivity and affinity, achieving potent antitumor effects at lower doses with minimal impact on normal tissues. Clinical trial results show that Birociclib significantly prolongs progression-free survival (PFS) and increases objective response rates (ORR), improving overall clinical outcomes without serious adverse events or notable drug interactions. The HR-positive/HER2-negative breast cancer treatment landscape already includes several widely used CDK4/6 inhibitors such as Pfizer’s Ibrance, Novartis’ Kisqali, and Eli Lilly’s Verzenio. These agents block tumor cell proliferation by targeting CDK4/6 and have proven effective in extending PFS and improving quality of life. However, variations in side effect profiles and tolerability among patients can limit their use. In comparison, Birociclib offers higher selectivity and a more favorable safety profile, providing a safer and more effective treatment option for patients. 5. Telisotuzumab Vedotin Telisotuzumab vedotin (ABBV-399, ABT-399), developed by AbbVie with support from Pierre Fabre SA, received its first approval in the United States on May 14, 2025, for the treatment of c-Met–positive non-squamous non-small cell lung cancer (NSCLC). Telisotuzumab vedotin is an antibody-drug conjugate (ADC) that exerts potent and selective anti-tumor activity by specifically binding to c-Met receptors on the surface of tumor cells and delivering the cytotoxic payload vedotin directly into the cancer cells. The antibody portion of the ADC is a humanized monoclonal antibody that selectively targets c-Met, a receptor that is overexpressed in various types of cancer, particularly in c-Met–positive non-squamous NSCLC. Upon binding to c-Met, the ADC is internalized into the tumor cell, where it releases the cytotoxin monomethyl auristatin E (MMAE), a microtubule inhibitor. MMAE disrupts microtubule polymerization, resulting in cell cycle arrest and apoptosis. Thanks to this targeted delivery mechanism, Telisotuzumab vedotin can efficiently kill tumor cells while sparing normal tissues, enhancing efficacy and minimizing systemic toxicity. Studies have shown that this targeted system improves antitumor activity and reduces adverse effects, offering a safer and more effective treatment option. Clinical results demonstrated that Telisotuzumab vedotin significantly prolonged progression-free survival (PFS) and improved objective response rates (ORR), with no serious adverse events or significant drug interactions observed. Currently, several targeted therapies and immune checkpoint inhibitors are widely used in the treatment of c-Met–positive non-squamous NSCLC, such as Merck’s Keytruda and Roche’s Tecentriq. However, these treatments primarily rely on stimulating the immune system to attack tumors and may have limited efficacy in tumors driven by specific mutations or overexpression, such as c-Met–positive NSCLC. In contrast, Telisotuzumab vedotin, as a novel ADC, offers precise and potent targeting of c-Met, presenting a new and effective therapeutic option. Other competing products include Capmatinib and Crizotinib, both of which are small-molecule c-Met inhibitors. However, these agents are often associated with higher toxicity and resistance issues, making Telisotuzumab vedotin a promising alternative. 6. Boryung Flu Vaccine V Boryung Flu Vaccine V (보령플루백신V주), developed by Boryung Biopharma, is a vaccine designed to prevent influenza A and B virus infections. It was first approved in South Korea on May 19, 2025, for the prevention of influenza A and B. Boryung Flu Vaccine V is an inactivated influenza vaccine prepared using killed strains of influenza A and B viruses. It works by introducing inactivated viral antigens into the body to stimulate the immune system to generate specific antibodies. The inactivated virus particles retain key surface antigens—hemagglutinin (HA) and neuraminidase (NA)—which are recognized and remembered by the immune system. Following vaccination, antigen-presenting cells capture and present these antigens to helper T cells and B cells, activating an adaptive immune response. B cells produce large quantities of antibodies, especially neutralizing antibodies that bind to the HA proteins on the virus surface, thereby blocking viral entry into host cells and preventing infection. In addition, memory B and T cells are generated, providing long-term immunity and enabling a rapid immune response upon re-exposure to the same or similar influenza viruses. Given the annual antigenic changes in circulating influenza strains, the formulation of Boryung Flu Vaccine V is updated annually based on recommendations from the World Health Organization (WHO) to ensure optimal protective efficacy. Currently, several influenza vaccines are widely available on the market, including Sanofi Pasteur’s Fluzone, GSK’s Fluarix, and AstraZeneca’s FluMist. These vaccines come in various forms, such as inactivated vaccines, live attenuated vaccines, and recombinant subunit vaccines. Each type has unique advantages and target populations. For instance, inactivated vaccines are suitable for most individuals, including the elderly and children; live attenuated vaccines are typically administered intranasally and are suitable for healthy individuals in specific age groups; recombinant vaccines are preferred for those with egg allergies or contraindications to traditional formulations. Compared to existing options, Boryung Flu Vaccine V, as a new-generation inactivated vaccine, demonstrates high immunogenicity and a strong safety profile, offering effective protection for a broad population. 7. Onradivir Onradivir (ZSP-1273), developed by Zhongsheng Pharmaceutical, was first approved in China on May 20, 2025, for the treatment of influenza A virus infections. Onradivir is a small-molecule antiviral agent specifically designed to inhibit RNA-dependent RNA polymerase (RdRp) of the influenza A virus, thereby blocking the viral replication process. RdRp is essential for synthesizing the viral genomic RNA, a key step in the propagation and transmission of the virus. Onradivir binds to RdRp, disrupting its normal function and preventing the synthesis of viral RNA, thus inhibiting replication within host cells. Studies show that Onradivir exhibits high selectivity and affinity, achieving potent antiviral effects at low concentrations while minimizing cytotoxicity to host cells. Moreover, because its mechanism of action targets a central step in the viral life cycle, Onradivir has a lower tendency to induce resistance mutations, giving it a potential advantage in long-term treatment. Compared to existing anti-influenza drugs such as Oseltamivir, which primarily inhibit viral neuraminidase, Onradivir directly targets a critical enzyme in viral replication, offering a more precise and effective therapeutic strategy. Clinical studies have demonstrated that Onradivir significantly shortens the duration of illness, reduces viral load, and improves clinical symptoms, accelerating patient recovery without causing severe adverse events or drug interactions. Zhongsheng Pharmaceutical has also utilized advanced drug design and manufacturing technologies to ensure high stability and bioavailability, with detailed pharmacokinetic studies indicating efficacy comparable to or better than existing influenza therapies. Post-marketing, the company continues to monitor the drug’s performance and plans to conduct Phase IV clinical trials to explore additional indications and long-term benefits. Currently, several antiviral drugs are available for treating influenza A virus infections, such as Tamiflu (Oseltamivir) by Roche and Relenza by GSK. These drugs function by inhibiting neuraminidase, preventing the release of newly formed viral particles from infected cells and slowing viral spread. However, the emergence of resistant viral strains has made the development of novel therapeutic strategies increasingly important. In this context, Onradivir, as a new RdRp inhibitor, provides a fundamentally different and more direct approach to suppressing viral replication. Other alternatives, such as Laninamivir by Merck, are long-acting neuraminidase inhibitors administered via a single inhalation dose, but their availability and use remain limited in certain regions. 8. Glecirasib Glecirasib Citrate, developed by Jacobio Pharmaceuticals Group Co., Ltd., was first approved in China on May 20, 2025, for the treatment of non-small cell lung cancer (NSCLC) with KRAS G12C mutation. Glecirasib is a selective small-molecule inhibitor that targets the KRAS G12C mutation, a known driver of oncogenesis in various cancers. It works by covalently binding to the cysteine residue at the G12C mutation site of the KRAS protein, thereby locking it in its inactive GDP-bound state and preventing downstream signaling activation. Under normal physiological conditions, KRAS functions as a molecular switch that toggles between an active (GTP-bound) and inactive (GDP-bound) state to regulate cell proliferation, differentiation, and survival. However, in tumors harboring the KRAS G12C mutation, the protein remains constitutively active, leading to continuous signal transduction and uncontrolled cell growth. Glecirasib’s covalent binding to the mutant site inhibits the RAS-RAF-MEK-ERK signaling cascade, effectively suppressing tumor cell growth and metastasis. Preclinical and clinical data demonstrate that Glecirasib offers high selectivity and potency, exerting strong antitumor effects at low doses while minimizing toxicity to normal tissues. Its unique mechanism of action also reduces the likelihood of resistance mutations, suggesting potential advantages for long-term therapy. Currently, other approved therapies for KRAS G12C-mutant NSCLC include Lumakras (Sotorasib) by Amgen and Adagrasib by Mirati Therapeutics. These drugs also inhibit KRAS G12C and have been shown to significantly extend progression-free survival and improve quality of life. However, some patients develop resistance or are unable to tolerate their side effects. In contrast, Glecirasib, as a next-generation KRAS G12C inhibitor, offers greater selectivity and a more favorable safety profile, providing a promising alternative for patients with this difficult-to-treat mutation. Other related therapeutic agents include Selumetinib by AstraZeneca, a MEK inhibitor used in the treatment of certain types of neurofibromatosis, which acts downstream of KRAS in the same signaling pathway. 9. Jaktinib Hydrochloride Jaktinib Hydrochloride, developed by Zelgen Biopharma Co., Ltd., was first approved in China on May 27, 2025, for the treatment of adult patients with intermediate- or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), and post-essential thrombocythemia myelofibrosis (PET-MF). It is indicated for the reduction of disease-related splenomegaly and symptoms. Jaktinib is the first domestically developed JAK inhibitor approved in China for myelofibrosis. It is a novel drug that inhibits JAK1, JAK2, JAK3, and TYK2, thereby blocking the JAK-STAT signaling pathway, which plays a central role in the pathogenesis of myelofibrosis. Additionally, it targets ACVR1, a receptor involved in iron metabolism, helping to correct iron dysregulation and improve anemia. In a Phase III clinical trial, 72.3% of patients achieved a ≥35% reduction in spleen volume (SVR35) at 24 weeks, significantly outperforming hydroxyurea (50%). Among patients who were refractory or intolerant to ruxolitinib, SVR35 was 43.2% in a Phase IIB trial and 32.4% in a Phase II trial. Jaktinib also showed notable efficacy in improving anemia and relieving symptoms (with 62% of patients experiencing a ≥50% reduction in total symptom score). Importantly, no Grade 3 or higher hematologic toxicities were reported, and gastrointestinal adverse events occurred at significantly lower rates than with similar agents. 10. Fovinaciclib Fovinaciclib Citrate (FCN-437), developed by Jinzhou Ahon Pharmaceutical, was first approved in China on May 27, 2025, for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer. Fovinaciclib is a selective CDK4/6 inhibitor that works by inhibiting the formation of CDK4/6–cyclin D complexes, thereby preventing the phosphorylation of the retinoblastoma (Rb) protein. The unphosphorylated Rb protein halts the cell cycle at the G1 phase, blocking progression into the S phase and inhibiting tumor cell proliferation. In HR+/HER2− breast cancer, the estrogen receptor (ER) signaling pathway is often activated, leading to upregulation of cyclin D and CDK4/6 activity, which promotes Rb phosphorylation and cell cycle progression. Fovinaciclib interrupts this process, thereby suppressing tumor growth and cell division. CDK4/6 inhibitors may also enhance immune recognition and cytotoxicity toward tumor cells, potentially synergizing with other immunotherapies. 11. Luvometinib Luvometinib (FCN-159), developed by Fochon Pharmaceuticals, was first approved in China on May 27, 2025. As a highly selective MEK1/2 inhibitor, Luvometinib was approved for the treatment of adult patients with Langerhans cell histiocytosis (LCH) or histiocytic tumors, as well as for children and adolescents aged 2 years and older with inoperable, symptomatic plexiform neurofibromas (PN) associated with neurofibromatosis type 1 (NF1). Luvometinib works by precisely inhibiting MEK1/2, key proteins in the MAPK signaling pathway, thereby blocking aberrant pathway activation. This inhibition suppresses tumor cell proliferation and induces apoptosis, delivering rapid clinical efficacy and a manageable safety profile. Compared to existing treatment options, Luvometinib offers a faster onset of action, providing new possibilities for clinical management. In addition to the approved indications, Luvometinib is also being investigated in other clinical trials, including a Phase III trial for NF1 in adults, and Phase II trials for conditions such as low-grade glioma and extracranial arteriovenous malformations. Several of these indications have been granted Breakthrough Therapy designation. 12. Trastuzumab Rezetecan Trastuzumab Rezetecan (SHR-A1811), developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd., is an antibody-drug conjugate (ADC) that was first approved in China on May 27, 2025, for the treatment of adult patients with locally advanced or metastatic HER2-mutant non-small cell lung cancer (NSCLC) who have received at least one prior systemic therapy. This approval was based on the results of the multicenter Phase 1/2 clinical study HORIZON-Lung, which demonstrated a remarkable objective response rate (ORR) of 74.5% and a median progression-free survival (mPFS) of 11.5 months. The incidence of interstitial lung disease (ILD) was only 8.5%, which is significantly lower than similar ADCs, offering a new "high-efficacy, low-toxicity" option for Chinese patients with HER2-mutant NSCLC. Trastuzumab Rezetecan consists of the trastuzumab backbone (SHR-1805), a GGFG linker, and a novel payload Rezivertinib, and incorporates three key proprietary innovations: ·Rezivertinib exhibits enhanced membrane permeability and cytotoxicity, increasing the bystander killing effect. ·It demonstrates a lower payload release rate in plasma compared to similar agents, enhancing safety. ·The DAR (drug-to-antibody ratio) of 6 is optimized to balance efficacy and toxicity. These features contribute to its superior antitumor activity and lower risk of adverse events. In the HORIZON-Lung trial, consistent efficacy and tolerability were observed regardless of brain metastasis status or prior TKI treatment. Subgroup analysis showed an ORR of 87.5% in patients with brain metastases and 81.8% in those previously treated with TKIs. Additionally, the 12-month overall survival rate was 88.2%, with a treatment discontinuation rate of only 2.1% due to adverse events and an ILD incidence of 8.5%. These results represent a significant milestone in HER2-mutant lung cancer treatment in China and set a new benchmark in global ADC development. 13. Human Papillomavirus Recombinant Vaccine (Cecolin 9) Cecolin 9 (Human papillomavirus recombinant vaccine nonavalent), developed by Innovax Biotech, was first approved in China on May 27, 2025. It covers seven high-risk HPV types (16, 18, 31, 33, 45, 52, and 58) and two low-risk types (6 and 11) and is indicated for females aged 9 to 45 years. This approval marks China as the second country in the world, after the United States, to independently supply a nonavalent HPV vaccine, enhancing vaccine accessibility and public health protection for women. 14. Albipagrastim Alfa Albipagrastim alfa (8MW0511, GW-003), developed by Mabwell (Shanghai) Bioscience Co., Ltd., was first approved in China on May 27, 2025. It is Mabwell’s first Class 1 innovative drug to be approved and the first granulocyte colony-stimulating factor (G-CSF) product in China developed using albumin-fusion long-acting technology. It is indicated for reducing the risk of infection in adult patients with non-myeloid malignancies undergoing myelosuppressive chemotherapy associated with febrile neutropenia (FN). Albipagrastim alfa fuses a highly active engineered G-CSF with human serum albumin (HSA), significantly prolonging its half-life and thus reducing dosing frequency and improving patient compliance. Compared to traditional chemically modified long-acting G-CSFs, it is produced via a Pichia pastoris expression system, offering a simpler manufacturing process and better product homogeneity. The use of natural human protein as a carrier further enhances safety. In a Phase III clinical trial involving 496 breast cancer patients, 8MW0511 outperformed the positive control drug Pegleukin in reducing the incidence of Grade 4 neutropenia and febrile neutropenia, with a favorable safety and tolerability profile. The approved indication targets chemotherapy-induced neutropenia, one of the most common hematologic toxicities in clinical oncology, especially with regimens containing paclitaxel, doxorubicin, or cyclophosphamide. According to statistics, the number of new global cancer cases is projected to reach 5.03 million in 2025, with a sharp rise in chemotherapy patients by 2040, indicating a promising market outlook for neutropenia prevention and treatment drugs. 15. Deuterated Enzalutamide Deuterated Enzalutamide (HC-1119), developed by Hinova Pharmaceuticals, was first approved in China on May 27, 2025, for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) who have disease progression after treatment with abiraterone acetate and chemotherapy, and have not previously received next-generation androgen receptor inhibitors. Deuterated enzalutamide is a second-generation androgen receptor (AR) inhibitor. Results from a Phase III clinical trial demonstrated that it significantly prolonged progression-free survival and reduced the risk of disease progression or death by 42% compared to the control group. Moreover, compared to other novel endocrine therapies, deuterated enzalutamide exhibited a favorable safety profile, with a lower incidence of central nervous system adverse events, reduced risk of rash-related side effects, and fewer common complications in elderly patients. 16. Lerociclib Lerociclib, jointly developed by Genor Biopharma and G1 Therapeutics (U.S.), was first approved in China on May 27, 2025. Lerociclib is a novel, potent, and highly selective oral CDK4/6 inhibitor designed for use in combination with endocrine therapy for the treatment of advanced breast cancer. The drug features a unique molecular structure and optimized pharmacokinetics, allowing continuous oral dosing without treatment breaks, thereby ensuring sustained target inhibition and robust antitumor activity. It also demonstrates a differentiated safety advantage. Clinical trials have shown that lerociclib delivers excellent efficacy in patients with endocrine-resistant and visceral metastatic advanced breast cancer, while also reducing common adverse events such as severe myelosuppression and diarrhea. It is indicated for adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, to be used either in combination with aromatase inhibitors as initial endocrine therapy or with fulvestrant in patients whose disease has progressed following prior endocrine therapy. 17. Famitinib Malate Famitinib Malate (SHR-1020), developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd., was first approved in China on May 27, 2025, for the treatment of patients with recurrent or metastatic cervical cancer who have failed prior platinum-based chemotherapy and have not been previously treated with bevacizumab. Famitinib is a small-molecule tyrosine kinase inhibitor (TKI) that targets PDGFR-β, VEGFR, and c-Kit, among others. By competitively binding to the intracellular tyrosine kinase domains, famitinib inhibits their phosphorylation, thereby blocking downstream signaling pathways and inhibiting tumor angiogenesis. Camrelizumab, a humanized PD-1 monoclonal antibody also developed by Hengrui, can be used in combination with famitinib to restructure the tumor vasculature and immune microenvironment, resulting in synergistic anti-tumor effects. Based on results from a randomized, open-label, controlled, multicenter Phase II clinical trial, the combination of famitinib and camrelizumab significantly improved objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Among patients who had not previously received bevacizumab, the combination therapy achieved an ORR of 44.6% compared to 22.6% with camrelizumab monotherapy. The median PFS reached 6.4 months, and median OS extended to 20.2 months. In terms of safety, the combination therapy did not introduce any new adverse event profiles, confirming its tolerability. 18. Acoltremon Acoltremon (AR-15512, TRYPTYR), developed by Alcon, was first approved in the United States on May 28, 2025, for the treatment of signs and symptoms of dry eye disease (DED). It is the first approved TRPM8 receptor agonist for DED, introducing a novel mechanism of action by stimulating corneal sensory nerves to rapidly promote natural tear secretion. The approval was based on results from two randomized, double-blind, controlled clinical trials—COMET-2 and COMET-3—involving a total of 931 patients with dry eye disease. The results showed that Tryptyr demonstrated significant efficacy early in treatment. On Day 14, the percentage of patients with an increase of ≥10 mm in tear secretion score from baseline was 42.6% and 53.2% in the two trials, respectively, significantly higher than the placebo groups. The improvement in tear production was sustained through Day 90, demonstrating long-lasting effects. The most common adverse event reported was instillation site pain. Tryptyr will be available in single-dose vials, administered as one drop in each eye twice daily. Alcon plans to launch the product in the U.S. in Q3 2025, followed by expansion into other markets. This innovative therapy offers a new treatment option for millions of dry eye patients worldwide. 19. mNEXSPIKE mNEXSPIKE (mRNA-1283), developed by ModernaTX, Inc., is an mRNA-based COVID-19 vaccine that was approved on May 31, 2025, for the prevention of COVID-19 caused by SARS-CoV-2. The approval specifically applies to two population groups: ·Individuals aged 65 and older who have previously received any COVID-19 vaccine ·Individuals aged 12 to 64 who have at least one underlying medical condition placing them at high risk of serious outcomes from COVID-19 infection mNEXSPIKE utilizes messenger RNA (mRNA) technology. It delivers an mRNA sequence encoding the spike (S) protein of SARS-CoV-2 into human cells, prompting temporary intracellular production of the antigen, which triggers both humoral and cellular immune responses. The mRNA is encapsulated in lipid nanoparticles (LNPs) to ensure stability and efficient cellular uptake. Once inside the host cell cytoplasm, the mRNA is translated into the S protein, which is then presented on the cell surface or secreted, activating antigen-presenting cells (such as dendritic cells), and stimulating B cells to generate neutralizing antibodies, while also promoting the formation of memory T cells. This dual immune activation mechanism allows mNEXSPIKE to not only neutralize the original SARS-CoV-2 strain, but also to offer broad protection against multiple variants. Compared to inactivated or recombinant protein-based vaccines, mNEXSPIKE provides higher immunogenicity, greater flexibility in sequence design, and faster manufacturing response times, making it particularly suited to address the evolving virus landscape. mNEXSPIKE has also been optimized in terms of dosage and storage compared to its predecessor, Spikevax. It uses one-fifth the dose and features improved shelf-life across various temperatures, owing to a shorter and more stable mRNA strand that encodes only the receptor-binding domain (RBD) and N-terminal domain (NTD) of the spike protein.   The month of May 2025 marked the approval of several milestone therapies that not only expanded the landscape of existing treatment options but also laid the foundation for transformative shifts in future medical practices. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!

ChenFJMU团队编辑（原创）思语湖畔QuoteLearning gives creativity. Creativity leads to thinking. Thinking provides knowledge. Knowledge makes you great.—Abdul KalamFDA新药速递【25年5月】看点FDA于2025年5月批准3款新药，分别为：治疗既往接受过系统治疗的KRAS突变复发性低级别浆液性卵巢癌（LGSOC）成年患者的Avmapki Fakzynja Co-Pack组合疗法；治疗局部晚期或转移性非鳞状非小细胞肺癌（NSCLC）的ADC药物Emrelis；治疗干眼症的Tryptyr眼药水。01首款联合疗法！Avmapki Fakzynja Co-Pack获FDA批准，专治KRAS突变的浆液性卵巢癌。02ADC药物突破性疗法！Emrelis: c-Met蛋白靶向的抗体药物偶联物治疗非鳞状非小细胞肺癌！03催泪神器，一天见效！TRPM8受体激动剂——Tryptyr获批上市用于治疗干眼症！细说FDA新药【25年5月】（ChenFJMU）Avmapki Fakzynja Co-Pack，01Avmapki Fakzynja Co-Pack（Avutometinib and defactinib，阿维替尼&地法替尼）是一种联合疗法，由Verastem Oncology公司研发，于2025年5月8日FDA加速批准上市，用于治疗既往接受过系统治疗的KRAS基因突变的复发性低级别浆液性卵巢癌（LGSOC）成年患者。该联合疗法是首个且唯一获得FDA批准的针对该疾病的药物。Avutometinib是一种新型口服RAF/MEK双重抑制剂，它不仅抑制MEK激酶活性，同时还防止上游RAF对MEK的代偿性再激活。Defactinib是黏着斑激酶（FAK，又称PTK2蛋白酪氨酸激酶2，PTK2）和富含脯氨酸的酪氨酸激酶-2（Pyk2）的抑制剂，它们是黏着斑激酶家族中非受体酪氨酸激酶的两个成员。FAK和Pyk2能够整合整合素和生长因子受体的信号，从而调节细胞的增殖、存活、迁移和侵袭。【结构与剂型处方】Avmapki Fakzynja Co-Pack是包含Avmapki（Avutometinib，阿维替尼）胶囊和阿维替尼（Defactinib，地法替尼）片剂的联用。Avmapki胶囊含有Avutometinib，这是一种激酶抑制剂。Avutometinib的化学名称是N-（3-氟-4-{[4-甲基-7-（2-嘧啶氧基）-2H-色原烯-2-酮-3-基]甲基}-2-吡啶基）-N’-甲磺酰胺钾盐。Avutometinib的分子式为C21H17FN5O5S（作为钾盐），其分子量为509.55。Avutometinib的化学结构如下图所示。阿维替尼钾是一种白色至淡黄色粉末。在水介质中，它在pH值1至7范围内几乎不溶。pKa为7.02。口服AVMAPKI胶囊含有0.8 mg阿维替尼（相当于0.864 mg阿维替尼钾盐），含有以下非活性成分：硬脂酸镁和甘露醇在羟丙甲纤维素胶囊外壳（角叉菜胶、羟丙甲纤维素、氯化钾、纯净水和氧化钛）中，印有黑色墨水（黑色氧化铁、丁醇、脱水酒精、异丙醇、氢氧化钾、丙二醇、纯净水、虫胶和强氨溶液）。Fakzynja片剂含有激酶抑制剂Defactinib，Defactinib的化学名称为N甲基-4-({4-[({3-甲基(甲磺酰基)氨基吡嗪-2-yl}甲基)氨基]-5-(三氟甲基)嘧啶-2-基}氨基)苯甲酰胺盐酸盐。Defactinib的分子式为C20ClH22F3N8O3S（作为盐酸盐），分子量为546.96。Defactinib的化学结构如下所示。盐酸地法替尼是一种白色至淡黄色粉末。它在pH值为1时极微溶，在pH值为4.5至6.8的水介质中几乎不溶。pKa为3.81。Fakzynja片剂可口服，每个Fakzynja片剂含有200 mg Defactinib（相当于214.36 mg的Defactinib盐酸盐）和以下非活性成分：一水合乳糖、硬脂酸镁、微晶纤维素和淀粉乙醇酸钠。【作用机制】RAS-RAF-MEK-ERK（MAPK）信号通路是细胞内重要的信号转导通路，可将细胞外刺激信号传递至细胞内，调控细胞多种生理功能。其过程为：细胞外生长因子与细胞膜上的受体酪氨酸激酶（RTKs）结合，引发RTKs二聚化和自身磷酸化，为含SH2结构域的鸟苷酸交换因子（GEFS）提供结合位点。GEFS与RTKs结合后，促使RAS蛋白结合GTP激活，激活的RAS蛋白招募并激活RAF蛋白，RAF蛋白磷酸化MEK蛋白使其激活，激活的MEK蛋白磷酸化ERK蛋白，激活后的ERK蛋白进入细胞核，磷酸化转录因子，调节细胞增殖、分化相关基因表达。即：细胞外生长因子→RTKs→RAS→RAF→MEK→ERK→核内转录调控。Avutometinib是一种RAF/MEK1抑制剂。Avutometinib诱导无活性RAF/MEK复合物的形成，并阻止RAF对MEK1/2的磷酸化。Avutometinib抑制MEK1/2和ERK1/2磷酸化和KRAS突变肿瘤细胞系的增殖。用Avutometinib治疗增加了磷酸化的黏着斑激酶（FAK）的水平。FAK和富含脯氨酸的酪氨酸激酶-2（Pyk2）是两种重要的非受体型酪氨酸激酶，它们在细胞信号转导中发挥关键作用。FAK和Pyk2可以通过多种机制激活RAS-RAF-MEK-ERK信号通路。Defactinib是FAK和Pyk2的抑制剂，抑制FAK自磷酸化。Avutometinib联合Defactinib可增强抗肿瘤作用。【药效学及药代动力学】药效学：Avutometinib和Defactinib的暴露-效应关系和药效反应时间过程尚未完全表征。在Avmapki Fakzynja Co-Pack的推荐剂量下（Avutometinib推荐剂量为3.2 mg，Defactinib推荐剂量为200 mg），没有观察到QTc间期>20 ms的平均增加。对于在RAMP-201（NCT04625270）中测量的88名PR间期患者，从基线到第1周期第15 d给药后4 h，平均PR间期增加了16 ms。药代动力学：Avutometinib在单次剂量范围为0.1~5 mg（批准推荐剂量的0.03~1.6倍）时表现出剂量比例增加的峰值血浆浓度（Cmax）和浓度时间曲线下面积（AUC）。在推荐剂量下没有观察到Avutometinib的显著积累。Defactinib在Cmax和AUC中表现出剂量比例增加，每日两次给药范围为12.5 mg至450 mg（批准推荐剂量的0.06至2.25倍）。Defactinib在大约15 d内达到稳态血浆浓度。在批准推荐剂量下，Defactinib积累为1.5倍。吸收：在禁食条件下，Avutometinib峰值血浆浓度（Tmax）的中位时间约为2 h。在进食条件下使用Defactinib的Tmax的中位时间约为4 h。高脂餐后Avutometinib的AUC无临床显著差异。高脂餐后Avutometinib Cmax降低了29%。使用高脂肪膳食后，Defactinib的AUC增加了2.7倍，Cmax增加了1.9倍。分布：Avutometinib稳态表观分布体积（Vd）为25 L（19%）。Avutometinib人血浆蛋白结合率为99%。Defactinib稳态表观Vd为1560 L（59%）。Defactinib人血浆蛋白体外结合率为90%。消除：Avutometinib消除半衰期为51 h（28%），表观口服清除率（CL/F）为0.3 L/h（30%）。Defactinib消除半衰期为9 h（171%），CL/F为69 L/h（173%）。代谢：Avutometinib主要通过CYP3A4和非酶降解代谢。Defactinib主要由CYP3A4和CYP2C9代谢。在血浆中鉴定出两种主要代谢物，N-去甲基磺胺（M2）和N-去甲基酰胺（M4）。M2和M4的AUC分别占Defactinib暴露的92%和28%。与Defactinib相比，M2是无活性的，M4是等效的。排泄：单剂量放射性标记的Avutometinib 2.4 mg（批准推荐剂量的0.8倍）后，粪便中恢复了39%（9.5%不变）的剂量，尿液中恢复了52%（3.2%不变）。单次剂量放射性标记的Defactinib 400 mg（批准推荐剂量的2倍）后，粪便中恢复了87%（52%不变）的剂量，尿液中恢复了7.6%（0.8%不变）。特定人群：轻度和中度肾损伤或轻度肝损伤，Avutometinib和Defactinib的药代动力学均没有观察到临床显著差异。重度肾损伤或中度至重度肝损伤对Avutometinib和Defactinib药代动力学的影响均尚不清楚。药物相互作用：强CYP3A4抑制剂：与伊曲康唑（强CYP3A4抑制剂）同时使用时，未观察到Avutometinib药代动力学的临床显著差异。与伊曲康唑（强力CYP3A4抑制剂）每天200 mg同时使用10 d后，Defactinib的Cmax增加了2.2倍，AUC增加了3.9倍。M4的AUC增加了2.2倍，Cmax减少了6.8%。强CYP3A4诱导剂：在与苯妥英（强CYP3A4诱导剂）联合给药23 d，3次/d，第17 d单次给药阿维替尼2.4 mg（批准推荐剂量的0.8倍）后，Avutometinib的AUC下降了34%，Cmax没有临床显着变化。与苯妥英（强CYP3A4诱导剂）联合给药23 d，3次/d，第14 d单次给药Defactinib 200 mg（批准推荐剂量的1.0倍）后，Defactinib的Cmax下降了83%，AUC下降了87%。M4的AUC下降了79%，Cmax下降了70%。质子泵抑制剂（PPIs）：Defactinib表现出pH依赖性的水溶解度。每天同时使用多剂量奥美拉唑（PPI）40 mg后，Defactinib的AUC下降了79%，Cmax下降了85%。M4的AUC下降了83%，Cmax下降了88%。。CYP450酶：Avutometinib是CYP3A4底物，但不是CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19和CYP2D6的底物。Avutometinib不是CYP3A4、CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19和CYP2D6的抑制剂。Avutometinib不是CYP3A4、CYP2B6和CYP1A2的诱导剂。Defactinib是CYP3A4和CYP2C9底物，但不是CYP1A2、CYP2B6、CYP2C8、CYP2C19和CYP2D6的底物。Defactinib是CYP3A4和CYP2C9的可逆抑制剂，但不是CYP1A2、CYP2B6、CYP2C8、CYP2C19和CYP2D6。Defactinib是CYP3A4的时间依赖性抑制剂。Defactinib是CYP2B6和CYP1A2的诱导剂，但不是CYP3A4的。UGT酶：Defactinib可能在临床相关浓度下抑制UGT1A1。     转运系统：Avutometinib是P-gp和BCRP的底物，但不是MATE1、MATE2-K、OAT1、OAT3、OATP1B1、OATP1B3、OCT1和OCT2的底物。Avutometinib不是P-gp、BCRP、MATE1、MATE2-K、OAT1、OAT3、OATP1B1、OATP1B3、OCT1和OCT2的抑制剂。Defactinib是BCRP和P-gp底物，但不是MATE1、MATE2-K、OAT1、OAT3、OATP1B1、OATP1B3、OCT1和OCT2的底物。Defactinib是P-gp、BCRP、OATP1B1、OATP1B3和MATE2-K的抑制剂，但不是MATE1、OAT1、OAT3、OCT1和OCT2的抑制剂。【非临床毒理学】目前还没有研究评估Avutometinib的致癌潜力。Avutometinib在细菌反向诱变（Ames）试验中没有诱变作用，在体外中国仓鼠肺染色体畸变试验或体内大鼠骨髓微核试验中没有致裂作用。尚未对Avutometinib进行专门的生育研究。尚未使用defactinib进行致癌性研究。Defactinib在细菌反向诱变（Ames）试验中无致突变性，在体外中国仓鼠肺细胞染色体畸变试验中无致裂性。Defactinib在体外微核试验中通过非基因机制和在体内大鼠骨髓微核试验中呈阳性。尚未使用Defactinib进行专门的生育研究。【动物毒理学和药理学】在大鼠和猴子长达13 w的重复剂量毒性研究中，观察到多个器官的组织矿化，剂量分别为≥0.01 mg /kg/d和0.03 mg /kg/d（分别为基于AUC的推荐剂量下人类暴露的≥0.06倍和1.4倍），以及大鼠无机磷的增加。在猴子的心电遥测监护研究中，单次口服Avutometinib使收缩压、舒张压和平均血压升高1 mg/kg（大约是推荐剂量下人类Cmax的15倍）。在长达13 w的大鼠重复剂量毒理学研究中，观察到心肌变性和坏死剂量≥0.01 mg/kg/d（低于基于AUC的推荐剂量下的人类暴露）。在一项狗的心电遥测监护研究中，单次口服Defactinib在剂量≥5 mg/kg时（大约是基于AUC的推荐剂量下的人类暴露）降低心肌收缩力，在剂量≥25 mg/kg/d时（≥2.7倍于基于AUC的推荐剂量下的人类暴露）增加心室收缩压、舒张压和平均血压。在狗的13 w重复剂量毒理学研究中，在剂量≥1 mg/kg/d时（低于基于AUC的推荐剂量下的人类暴露），在剂量和恢复期结束时观察到心肌肥大。【临床研究】Avmapki Fakzynja Co-Pack的疗效在一项开放标签、多中心研究RAMP-201（NCT04625270）中进行了评估，有57名可测量的KRAS突变复发性LGSOC成年患者。患者至少接受过一次全身治疗，包括基于铂的治疗。KRAS突变状态通过使用肿瘤组织标本的下一代测序（NGS）或聚合酶链反应的前瞻性局部测试来确定。如果患者准备接受是去角质手术、正在接受华法林治疗、在过去一年中有需要全身治疗的活动性皮肤病或有眼部疾病（包括视网膜病理学史、活动性或慢性视觉显着性角膜疾病或青光眼），则被排除在外。通过局部测试确定的KRAS突变是G12V（53%）、G12D（35%）、Q61H（3.5%）、G12C（1.8%）、G12R（1.8%）、A146V（1.8%）以及G12x（1.8%）和密码子12/13（1.8%）处明确指定的突变。14%的患者接受过1次全身治疗，25%的患者接受过2次全身治疗，18%接受过3次全身治疗，40%接受过3次以上全身治疗。所有患者都接受过铂类化疗，84%接受过激素治疗（作为维持或治疗），40%接受过贝伐单抗，21%接受过MEK抑制剂。    患者在4周周期的前3周每周两次口服Avutometinib 3.2 mg，在4周周期的前3周每天两次口服Defactinib 200 mg，直到疾病进展或不可接受的毒性。主要疗效结果测量是由盲法独立审查委员会（BIRC）根据实体肿瘤反应评估标准（RECIST）1.1版评估的总体反应率（ORR）。次要疗效结果测量是反应持续时间（DoR）。前72周每8周进行一次肿瘤反应评估，此后每12周进行一次。疗效结果如表5所示，主要疗效结果DRR占比44%，次要疗效结果DoR范围为3.3个月至31.1个月。40%。在25名应答者中观察到的肿瘤KRAS突变为A146V、G12D、G12R、G12V和Q61H。【用药指南】Emrelis，02Emrelis（Telisotuzumab vedotin-tllv，维汀-特立妥珠单抗ADC药物），由艾伯维公司研发，于2025年5月14日获FDA批准上市。Emrelis 是一种靶向 c-Met 蛋白受体的抗体-药物偶联物，治疗既往已接受过全身治疗且高度 c-Met 蛋白过表达的局部晚期或转移性非鳞状非小细胞肺癌（NSCLC）成年患者。该疗法2022年1月被FDA授予突破性疗法认定。此外，获得FDA批准的治疗既往已接受过全身治疗且高度 c-Met 蛋白过表达的局部晚期或转移性非鳞状非小细胞肺癌的药物还有2020年获批的Tabrecta（Capmatinib，卡马替尼）、2021年获批的Tepmetko（tepotinib，特泊替尼）和Orpathys（Savolitinib，赛沃替尼）。【结构与剂型处方】Emrelis是一种由人源化免疫球蛋白G1k（IgG1k）单抗与小分子微管破坏剂单甲基奥瑞斯汀E（MMAE）通过蛋白酶可切割的缬氨酸-瓜氨酸（vc）连接臂连接而成的c-Met靶向抗体药物偶联物（ADC）。每个单克隆抗体分子平均携带3个MMAE分子。其分子量约为152 kDa。Emrelis注射液是一种无菌、白色至灰白色的冻干粉，不含防腐剂，每瓶装有单剂量，需在静脉输注前进行复溶和稀释。Emrelis提供20 mg或100 mg的剂量，使用无菌注射用水复溶后，每毫升溶液含有20 mg的Telisotuzumab，以及组氨酸（2.33 mg）、聚山梨酯80（0.10 mg）、蔗糖（70.0 mg）和注射用水。最后加入盐酸调节pH值至6.0。【作用机制】c-Met 是一个关键的受体酪氨酸激酶，其正常生理功能对发育和修复至关重要。然而，其信号通路的异常激活是驱动多种癌症恶性进展的核心机制。因此，c-Met已成为抗癌药物研发的重要靶点。Telisotuzumab是一种针对c-Met的抗体药物偶联物（ADC）。该抗体是一种人源化的IgG1k抗体，靶向肝细胞生长因子的细胞表面受体c-Met。小分子MMAE是一种微管破坏剂，通过一个蛋白酶可切割的连接子与抗体相连。当Telisotuzumab与过表达c-Met的细胞结合后，会进入细胞内部并裂解释放MMAE。MMAE破坏活跃分裂细胞的微管网络，导致细胞周期停滞和细胞凋亡。在NSCLC异种移植模型中，能够精准地向表达c-Met的肿瘤细胞输送细胞毒性有效载荷，为非小细胞肺癌患者提供了一种新的治疗策略。【药效学及药代动力学】药效学：疗效和药效学反应时程的暴露-效应关系尚未得到充分表征。Telisotuzumab暴露量增加与3级周围神经病变、2级和3级眼表疾病的发生率增加相关。非结合MMAE暴露量增加与≥3级不良反应和致死性不良反应的发生率增加相关。药代动力学：吸收：Telisotuzumab达到最大血浆浓度的时间（Tmax）发生在静脉输注结束时，而MMAE的Tmax发生在给药后约5 d。分布：Telisotuzumab的分布容积为3.4 L。体外MMAE血浆蛋白结合率的范围为68%至82%。消除：Telisotuzumab的消除半衰期约为3 d，MMAE约为4 d。Telisotuzumab的清除率为1.3 L/d，MMAE为76 L/d。代谢：Telisotuzumab会分解代谢为小肽、氨基酸、未缀合的MMAE和未缀合的MMAE相关催化剂。特殊人群用药：孕妇：Telisotuzumab可能对胎儿造成伤害，并且损害生育能力。儿科：Telisotuzumab在儿科患者中的安全性和有效性尚未得到证实。肝损害患者：中度或重度肝功能损害患者避免使用Telisotuzumab。药物相互作用：Telisotuzumab与其他药物共同使用时的药代动力学效应尚未研究。免疫原性：对269位接受Telisotuzumab治疗的患者进行抗药物抗体（ADA）研究，有 22%（60/269）的患者出现Telisotuzumab抗体。38%（23/60）的患者检测到中和抗体，17%（23/60）的患者出现抗药物抗体和中和抗体，没有足够的数据来评估所观察到的抗Telisotuzumab抗体相关的药代动力学变化是否影响Telisotuzumab的安全性和有效性。【非临床毒理学】Telisotuzumab可能存在生殖毒性和遗传毒性；无致突变性；尚未进行致癌性研究。【临床研究】Telisotuzumab在一项多中心、随机、单组，多队列临床试验（NCT03539536）中进行疗效评估。符合条件的患者需要患有局部晚期或转移性NSCLC伴c-Met蛋白过表达，并接受过既往全身治疗。患者每2周接受1次1.9 mg/kg的Telisotuzumab静脉给药，直至疾病进展或出现不可接受的毒性。主要疗效指标是由设盲的独立审查委员会（BIRC）使用RECIST v1.1评估的总缓解率（ORR）和反应持续时间（DOR）。结果如表所示，受试者的ORR为35%，DOR为7.2个月。【用药指南】Tryptyr，03Tryptyr(Acoltremon，阿科特雷蒙），由爱尔康公司所研发，于2025年5月28日获FDA批准上市。Acoltremon是首款获批用于治疗干眼症的“First-in-Class”瞬时受体电位8型（TRPM8）受体局部激动剂。目前，使用人工泪液是治疗干眼症的常用方法，但大多数患者未能获得满意的治疗结果。Acoltremon的获批为治疗干眼症提供了一种全新的作用机制，有望很快惠及更多干眼症患者。【结构与剂型处方】Tryptyr (Acoltremon眼药水）0.003%含有TRPM8离子通道激动剂。Acoltremon的化学名称为(1R,2S,5R)-2-异丙基-n-（4-甲氧基苯基）-5-甲基环己烷-1-羧酰胺。Acoltremon的分子式为C18H27NO2，分子量为289.42 g/mol。Acoltremon是一种白色到淡黄色的结晶固体，不溶于水。Tryptyr滴眼剂是一种无菌、透明至微乳白色、无色等渗溶液，用于眼科外用，pH值约为7，渗透压为280至330 mOsm/kg。每mL的Tryptyr含有活性：0.003%的Acoltremon；非活性物质：聚氧35蓖麻油，磷酸二氢钠，氯化钠，羟丙纤维素和纯净水。Tryptyr不含抗微生物防腐剂。【作用机制】干眼症是最常见的眼部慢性疾病之一，由自然泪液分泌不足等复杂多因素引起，造成持续的刺痛、烧灼感、对光敏感、视力模糊和眼疲劳。Acoltremon是一款瞬时受体电位8型(TRPM8)受体激动剂，与TRPMB受体结合后，刺激TRPM8热感受器，将信号传递至角膜感觉神经，有效激活三叉神经信号，快速增加自然泪液的分泌，直接解决干眼症泪液缺乏的问题。【药效学及药代动力学】药代动力学：在第1、14和90天对25例干眼病患者进行PK评估，这些患者接受了Acoltremon（1滴，每天两次）治疗。共有3例（12.0%）血药浓度高于20 pg/mL（定量下限），最高血药浓度为213 pg/mL。特殊人群用药：1、儿科患者：Acoltremon在儿科患者中的安全性和有效性尚未得到证实。2、孕妇：Acoltremon未观察到母体或胎儿的毒性。3、老年：Acoltremon在老年和年轻患者之间没有观察到临床相关的安全性差异。【非临床毒理学】Acoltremon尚未进行致癌性和生育能力研究；Acoltremon无致突变性。【临床研究】两项随机、多中心、双盲、载体对照研究（COMET-2 [NCT-05285644]和COMET-3 [NCT-05360966]）支持了Acoltremon治疗干眼症的疗效。患者按1:1的比例随机分配到Acoltremon或对照剂（安慰剂），每天两次，持续90天。研究期间不允许使用人工泪液。结果如图所示，在第14天（主要终点）使用Acoltremon治疗的患者中，COMET-2研究中42.6%的患者的Schirmer评分较基线增加≥10 mm， COMET-3研究中53.2%的患者在第14天的Schirmer评分较基线增加≥10 mm，而在COMET-2研究和COMET-3研究中，分别有8.2%和14.4%的患者接受了载体治疗。两项研究均观察到Acoltremon组与安慰剂相比泪液生成具有统计学差异。【用药指南】编辑：蔡栅愉排版：周纯情补充和审核：陈昌买推送：ChenFJMU（欢迎个人转发分享，企业及其他公众号需授权后转载，并注明出处！）