Tezepelumab

Tezepelumab is a human monoclonal antibody of the type IgG2λ (immunoglobulin G2λ), which is produced in Chinese hamster ovary cells (CHO cells) using recombinant DNA technology. It has a molar mass of around 148 kDa. The monoclonal antibody neutralizes the cytokine TSLP(thymic stromal lymphopoietin), which is produced in skin and mucosal epithelia.

Tezepelumab intervenes very early in the inflammatory cascade. TSLP activates antigen-presenting cells and is thus intended to initiate an immunological response. In asthma, both allergic and non-allergic triggers induce TSLP production.

TSLP is mainly released from epithelial cells and plays a role at an early stage in the inflammatory cascade, for example in bronchial asthma, atopic dermatitis and other inflammatory diseases. Blocking TSLP with tezepelumab reduces a broad spectrum of biomarkers and cytokines associated with airway inflammation (e.g. eosinophils in the blood or airway mucosa, IgE, FeNO, IL-5 and IL-13).

Tezepelumab is a human monoclonal antibody (IgG2λ) that is degraded by proteolytic enzymes widely present in the body. Tezepelumab is not metabolized by liver enzymes. As a human monoclonal antibody, tezepelumab is eliminated by intracellular catabolism. The elimination half-life is approximately 26 days.

After a single subcutaneous administration, the maximum serum concentration was reached within approx. 3 to 10 days. The estimated absolute bioavailability is approx. 77%. There was no clinically relevant difference in bioavailability when administered at different injection sites (abdomen, thigh or upper arm).

To date, there is no or only very limited experience (less than 300 pregnancies) with the use of tezepelumab in pregnant women. Animal studies have shown no evidence of direct or indirect adverse health effects related to reproductive toxicity. Human IgG antibodies, such as tezepelumab, are transported across the placental barrier; for this reason, tezepelumab can pass from the mother to the developing fetus. As a precaution, use of Tezspire during pregnancy should be avoided unless the anticipated benefit to the pregnant mother outweighs any potential risk to the unborn child.

Lactation: Human IgG antibodies are known to pass into breast milk within the first few days after birth, reducing to low levels shortly thereafter.

Tezepelumab is administered as a subcutaneous injection and should be injected into the thigh or abdominal skin. After training in the subcutaneous injection technique, patients can inject themselves or have their caregivers inject them.

The recommended dose is 210 mg tezepelumab as a subcutaneous injection every 4 weeks.

The most commonly reported side effects that occurred in the clinical trials with tezepelumab were:

• Pharyngitis
• exanthema
• arthralgias
• Reactions at the injection site

No studies have been conducted to detect interactions. The use of live attenuated vaccines should be avoided in patients receiving tezepelumab. Tezepelumab is not expected to have a clinically relevant effect on the pharmacokinetics of concomitant asthma medications.

Tezepelumab must not be used in case of hypersensitivity to the active substance or any of the other ingredients of the medicinal product.

Tezspire (AstraZeneca / Amgen)

Under the name Tezspire (AstraZeneca / Amgen), it was approved in the USA in December 2021 and in the EU in September 2022 for the adjunctive maintenance treatment of severe, uncontrolled bronchial asthma in patients aged 12 and over.

1. Corren J et al. (2021) Tezepelumab improves patient-reported outcomes in patients with severe, uncontrolled asthma in PATHWAY. Annals of Allergy, Asthma & Immunology 126: 187-193.
2. Marone G et al. (2019) Tezepelumab: a novel biological therapy for the treatment of severe uncontrolled asthma. Expert Opinion on Investigational Drugs 28: 931-940.
3. Menzies-Gow A et al. (2021) Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. In: The New England Journal of Medicine 384: 1800-1809.
4. Nolasco S et al. (2022) Tezepelumab for asthma. Drugs Today (Barc) 58:591-603.