What Is Penpulimab-kcqx (Anike)? FDA Approval, Licensing in Turkey, and Reimbursement

• FDA Approval: Yes (Initial Approval Date: April 23, 2025)
• Brand Name: Anike
• Active Ingredient: Penpulimab-kcqx
• Route of Administration: Intravenous infusion (IV)
• Class: Immune checkpoint inhibitor (anti-PD-1 monoclonal antibody)
• Category: Antineoplastic agent (immunotherapy)
• Manufacturer: Akeso Biopharma Co.Ltd.
• Availability in Turkey: It is not currently licensed in Turkey. However, access may be possible through overseas medicine supply programs.
• Approved Cancer Indications: As a single agent, treatment of metastatic nonkeratinizing nasopharyngeal carcinoma in adults whose disease has progressed after platinum-based chemotherapy and at least one prior systemic treatment.

What Is Penpulimab-kcqx (Anike)? How Does It Work?

Penpulimab-kcqx is an immunotherapy agent that helps the immune system recognize and destroy cancer cells. It was developed for use alone or with chemotherapy in certain head and neck cancers, particularly nonkeratinizing nasopharyngeal carcinoma, when disease is advanced or metastatic. Its active ingredient is a modified anti-PD-1 monoclonal antibody derived from the human IgG1 isotype.

How Does It Work?

Penpulimab binds with high specificity to PD-1 (programmed cell death protein 1) on T lymphocytes, a type of immune cell. Cancer cells express proteins called PD-L1/PD-L2 on their surfaces, activating PD-1 and "silencing" T cells. By binding to PD-1, penpulimab disrupts this inhibitory interaction. T cells are thereby reactivated and can recognize and attack tumor cells. Despite its gG1 antibody framework, its Fc region is modified, helping prevent unwanted destructive immune responses such as ADCC and CDC. This provides more controlled, selective immune activation. The antibody's structural stability has been increased with the aim of prolonging its time in circulation.

FDA (US Food and Drug Administration) Approval History

• May 24, 2021: Akeso submitted a Biologics License Application (BLA) in the US for its monoclonal antibody penpulimab.
• April 24, 2025: The FDA approved penpulimab-kcqx for treating advanced nasopharyngeal carcinoma.

Licensing in Turkey

It has not yet been officially licensed in Turkey. It may be obtained from abroad under the Ministry of Health's special authorization procedures. It is not included in the TİCK overseas medicines list.

Mechanisms of Resistance

• Low or Heterogeneous PD-L1 Expression: Penpulimab blocks the PD-1/PD-L1 interaction. If tumor cells express low levels of PD-L1, or expression is heterogeneous, treatment cannot provide adequate immune activation. This is particularly important in primary resistance.
• Tumor Microsatellite Instability and Low Mutational Burden:  Low tumor mutational burden (TMB) and microsatellite stability result in fewer neoantigens for the immune system to recognize. Consequently, T cells fail to "see" the tumor.
• Impaired Antigen Presentation: Cancer cells may reduce or lose expression of MHC class I molecules, preventing T cells from recognizing them. B2M (beta-2 microglobulin) mutations can also completely disable antigen presentation.
•  Immunosuppressive Tumor Microenvironment (TME): Suppressive cells may surround the tumor, including regulatory T cells (Treg), M2 macrophages, and MDS (Myeloid-derived suppressor cells). These cells secrete cytokines such as IL-10 and TGF-β, suppressing T-cell activity.
• Activation of Alternative Immune Checkpoints: Despite PD-1 blockade, the tumor may activate other pathways. Checkpoints such as TIM-3, LAG-3, and TIGIT may take on an inhibitory role, enabling immune escape. This generally occurs in secondary resistance.
• Changes in Inflammatory Signaling Pathways: Mutations in the IFN-γ signaling pathway weaken T-cell-mediated immune responses. JAK1/JAK2 mutations are known genetic causes of this process.

Absorption

• Penpulimab is administered by intravenous infusion, so gastrointestinal absorption, as occurs with conventional medicines, is not involved.
• Bioavailability is 100% because it is delivered directly into the systemic circulation.
• Maximum plasma concentration (Cmax) is generally reached at the end of the infusion.
• The absorption rate is directly related to infusion duration and dose.

Distribution

• Penpulimab is a large IgG1 monoclonal antibody. Its distribution is therefore confined to extracellular fluid compartments.
• The volume of distribution is low, approximately 4–6 L, indicating that the medicine is found mainly in plasma and lymphatic fluid.
• It does not enter cells directly; it acts by binding to PD-1 receptors on the cell surface.
• Tissue selectivity depends on PD-1 expression, so localization may be greater in tissues rich in immune cells.

Metabolism

• Unlike conventional small-molecule drugs, penpulimab is not metabolized by hepatic CYP450 enzymes.
• Monoclonal antibodies are broken down by intracellular lysosomal enzymes in the body.
• The resulting peptides and amino acids enter the body's natural protein pool or are recycled.
• Dose adjustment is therefore generally unnecessary in patients with hepatic impairment, although careful monitoring is recommended.

Elimination

• Penpulimab is eliminated through cellular breakdown in the reticuloendothelial system rather than through conventional renal or biliary routes.
• Plasma clearance is slow. Half-life (t½): Approximately 17–22 days, varying with the patient, dose, and immune activity.
• Elimination products are broken down into small peptides and amino acids, which are generally incorporated into metabolic processes before urinary or biliary excretion.

Dosing Schedule

• Monotherapy (Use Alone): 200 mg by intravenous infusion every 2 weeks, for a maximum of 24 months or until disease progression.
• Combination Treatment (With Chemotherapy): 200 mg by intravenous infusion every 3 weeks, usually with gemcitabine + platinum-based chemotherapy (cisplatin or carboplatin). It may continue throughout chemotherapy and then as maintenance for up to 24 months.
• The first infusion generally takes 30–60 minutes; subsequent infusions may be administered more quickly if well tolerated.
• Premedication before infusion is generally unnecessary because infusion reactions are rare owing to the Fc modification.

Drug Interactions

• Interactions With Cytochrome P450 (CYP) Enzymes: Penpulimab is not metabolized by the liver's CYP450 enzyme system. Direct interactions with CYP3A4 inducers or inhibitors are therefore not expected. No special precautions are required when it is used with CYP-affecting agents such as antiepileptics, antifungals, or macrolide antibiotics.
• Combination With Other Anticancer Agents: No significant pharmacokinetic interaction has been observed when penpulimab is used with chemotherapy, such as gemcitabine + platinum agents. However, caution is needed regarding combined toxicity. Myelosuppression, gastrointestinal toxicity, and immune-related adverse effects may be increased.
• Interactions With Immunosuppressive Medicines: Corticosteroids and other immunosuppressive agents may weaken the mechanism by which penpulimab activates the immune system. However, short-term, controlled steroid treatment used to manage immune-related adverse effects does not completely preclude treatment. High-dose or prolonged steroid use may reduce penpulimab's effect.
• Vaccine Interactions: Live vaccines, such as MMR and yellow fever vaccines, are not recommended during penpulimab treatment. Inactivated vaccines, such as influenza and inactivated COVID-19 vaccines, may be given, although the immune response may be weak.

Precautions

Immune-Related Adverse Effects: Immunotherapies such as PD-1 inhibitors may cause the immune system to attack normal tissues as well as the tumor. The most common effects include:

• Pneumonitis (lung inflammation): Cough and shortness of breath
• Colitis: Diarrhea and abdominal pain
• Hepatitis: Elevated transaminases
• Thyroiditis / hypothyroidism: Weakness, weight gain, and elevated TSH
• Skin rashes and itching

These effects can range from mild to life-threatening. Early recognition and steroid treatment, such as prednisone, when needed are important.

Patients With a History of Autoimmune Disease: Patients with active or uncontrolled autoimmune disease, such as lupus or rheumatoid arthritis, may have an increased risk of a disease flare. Penpulimab should be used in these patients only after careful assessment of benefits and harms.

Infections and Immunosuppression: Penpulimab should not be started in the presence of an active serious infection, particularly tuberculosis or hepatitis B/C. Concomitant immunosuppressive medicines may reduce treatment effectiveness and increase infection risk.

Monitoring Liver and Thyroid Function: Parameters such as ALT/AST, bilirubin, TSH, and FT4 should be monitored before treatment and periodically thereafter. Subclinical thyroiditis or hepatotoxicity is easier to manage when identified early.

Vaccination: Live vaccines, such as measles and yellow fever vaccines, are strongly discouraged during treatment. Inactivated vaccines may be administered, although the immune response may be weak. COVID-19 and influenza vaccines are included in this group.

Pregnancy and Breastfeeding: Adequate data on penpulimab use during pregnancy are lacking. However, PD-1 inhibitors may theoretically cross the placenta and cause immune effects in the fetus. Use during pregnancy and breastfeeding is not recommended. Effective contraception should be used throughout treatment and for at least 5 months afterward.

Infusion Reactions: Although rare, allergic reactions, chills, fever, and hypotension may occur. Patients should be monitored closely during initial administrations. Premedication, such as an antihistamine, may be given if needed.

Adverse Effects

• Fatigue 31%
• Loss of appetite 27%
• Nausea 26%
• Hypothyroidism 25%
• Weight loss 24%
• Constipation 23%
• Vomiting 22%
• Cough 21%
• Rash 20%
• Fever 20%
• Anemia 19%
• Headache 17%
• Abdominal pain 15%
• Diarrhea 14%
• Arthralgia (joint pain) 13%
• Itching (pruritus) 12%
• Dizziness 11%
• Shortness of breath 10%
• Upper respiratory tract infection 9%
• Pneumonitis (immune-related lung inflammation) 7%
• Elevated transaminases (ALT/AST) 6%
• Thyroiditis 5%
• Hyperglycemia 4%
• Immune-related colitis 3%
• Infusion reaction 2%

These rates were compiled from phase 2–3 clinical trials involving patients receiving single-agent treatment or combination treatment with chemotherapy. Adverse effects were generally grade 1 or 2 (mild to moderate). More serious toxicities may require clinical intervention and immunosuppressive treatment.