Cemiplimab API Manufacturers

General Description:

Cemiplimab, identified by CAS number 1801342-60-8, is a notable compound with significant therapeutic applications. Cemiplimab is a fully human monoclonal antibody that works against programmed death receptor-1 (PD-1), which is a negative regulator of T cell function. By blocking PD-1, cemiplimab works to enhance T cell-mediated antitumour responses. Cemiplimab was first approved by the FDA on September 28, 2018, as the first FDA-approved treatment for advanced cutaneous squamous cell carcinoma (CSCC). It was later approved to be used in basal cell carcinoma and non-small non-small cell lung cancer. Cemiplimab was also approved by the European Commission on June 28, 2019. In October 2022, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended cemiplimab be granted marketing authorization for the treatment of cervical cancer.

Indications:

This drug is primarily indicated for: Cemiplimab is indicated to treat: - Locally advanced or metastatic cutaneous squamous cell carcinoma (mCSCC) in patients who are not candidates for curative surgery or curative radiation. - Locally advanced basal cell carcinoma (laBCC) in previously treated patients with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. - Metastatic basal cell carcinoma (mBCC) in patients who were previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. This indication is approved under accelerated approval based on tumour response rate and durability of response. Continued approval for mBCC may be contingent upon verification and description of clinical benefit. - Locally advanced non-small cell lung cancer (NSCLC) in combination with platinum‐based chemotherapy for the first‐line treatment of adults with no EGFR, ALK or ROS1 aberrations, who are not candidates for surgical resection or definitive chemoradiation. It is also indicated to treat metastatic NSCLC in combination with platinum‐based chemotherapy as first-line treatment in adults. - Locally advanced or metastatic NSCLC as monotherapy for the first-line treatment of adults whose tumours have high PD-L1 expression as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations. Patients with locally advanced NSCLC must not be candidates for surgical resection or definitive chemoradiation. - Recurrent or metastatic cervical cancer in adults with disease progression on or after platinum-based chemotherapy. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Cemiplimab undergoes metabolic processing primarily in: As with other monoclonal antibodies, cemiplimab is expected to undergo nonspecific degradation into small peptides and individual amino acids. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Cemiplimab are crucial for its therapeutic efficacy: In a pharmacokinetic study involving patients with various solid tumours, the pharmacokinetics of cemiplimab was linear and dose-proportional in the dose range of 1 mg/kg to 10 mg/kg cemiplimab administered intravenously every two weeks. When cemiplimab was administered at a dose of 350 mg every three weeks, the median steady-state concentrations (coefficient of variation, CV%) of cemiplimab ranged between 61 mg/L (45%) and 171 mg/L (28%). Steady-state exposure is achieved after four months of treatment. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Cemiplimab is an important consideration for its dosing schedule: The elimination half-life (CV%) at steady state is 20.3 days (29%). This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Cemiplimab exhibits a strong affinity for binding with plasma proteins: No information is available. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Cemiplimab from the body primarily occurs through: No information is available. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Cemiplimab is distributed throughout the body with a volume of distribution of: The volume of distribution (coefficient of variation, CV%) of cemiplimab at steady-state is 5.3 L (26%). This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Cemiplimab is a critical factor in determining its safe and effective dosage: Cemiplimab clearance (CV%) after the first dose is 0.29 L/day (33%) and decreases over time by 29%, resulting in a steady-state clearance (CL_ss) (CV%) of 0.2 L/day (40%). It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Cemiplimab exerts its therapeutic effects through: Cemiplimab inhibits tumour growth via an immune-mediated mechanism. Cemiplimab works to promote T cell-mediated immune response against tumours by blocking programmed death-1 (PD-1), a negative regulator of T cells. Cemiplimab targets PD-1 with high affinity and potency. In syngeneic mouse tumour models, blocking PD-1 activity by cemiplimab resulted in decreased tumour growth. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Cemiplimab functions by: T cells mediate antitumour activity following activation by antigen receptor signalling and CD28 costimulatory signalling. T cell proliferation and activation are regulated by a number of T cell immune regulatory checkpoints, including programmed death-1 (PD-1). PD-1 is an inhibitory co-receptor that is predominantly expressed on the surface of T cells to block T cell activation. Its ligands, PD-L1 and PD-L2, bind to PD-1 to activate downstream signalling cascades that ultimately result in the inhibition of T cell function such as T cell proliferation, cytokine production, and cytotoxicity. PD-1 receptor signalling pathway serves to maintain tolerance and regulate any ineffective or harmful immune responses; however, PD-1 signalling can also attenuate immune responses in cases where such protection is needed, such as autoimmune disorders and malignancy. PD-L1 and PD-L2 are expressed on antigen-presenting cells (APCs) as well as on some types of tumour cells as part of an adaptive immune response by tumours. PD-1 is also upregulated in some cancers, impeding T cell-mediated antitumour activity. Cemiplimab is a human PD-1-blocking antibody that binds to PD-1 and blocks its interaction with its ligands. By disinhibiting PD-1 mediated suppression of T cell activity, cemiplimab works to potentiate T cell cytotoxicity against tumours. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Cemiplimab belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Cemiplimab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antineoplastic Agents, Antineoplastic Agents, Immunological, Antineoplastic and Immunomodulating Agents, Blood Proteins, Cancer immunotherapy, Globulins, Immune Checkpoint Inhibitors, Immunoglobulins, Immunoproteins, Immunotherapy, MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES, Narrow Therapeutic Index Drugs, PD-1/PDL-1 (Programmed cell death protein 1/death ligand 1) inhibitors, Programmed Death Receptor-1 Blocking Antibody, Proteins, Serum Globulins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Cemiplimab include:

• Molecular Weight: 146000.0
• Molecular Formula: C6380H9808N1688O2000S44