Libtayo (cemiplimab-rwlc) is an advanced fully human monoclonal antibody indicated for the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) in patients ineligible to undergo curative surgery or radiation therapy.

Developed by Regeneron using its proprietary VelocImmune® technology, Libtayo is approved in the US and is being jointly marketed by Regeneron and Sanofi Genzyme as part of a collaboration agreement between the two companies.

The US Food and Drug Administration (FDA) granted breakthrough therapy designation for Libtayo in September 2017. The biologics license application (BLA) for Libtayo was accepted for priority review in April 2018. The drug was approved by the FDA for the treatment metastatic or locally advanced CSCC in September 2018.

Regeneron and Sanofi Genzyme submitted a marketing authorisation application (MAA) to the European Medical Agency (EMA) for Libtayo, which was accepted for review in April 2018. The review process was completed in the first half of 2019.

In July 2019, Libtayo received approval from the European Commission (EC) for use in adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma.

Cutaneous squamous cell Carcinoma causes and symptoms

CSCC is a type of skin cancer arising from the uncontrolled growth of cells in the upper layers of the skin, often characterised by a presence of persistent scaly patches, open sores, warts and elevated growths with a central depression, which may crust and bleed.

The most common causes of CSCC are long-term exposure to ultraviolet (UV) radiation from sunlight and the use of indoor tanning. However, it can also be caused by skin injuries such as scars, long-standing sores, burns, ulcers, chronic infections, skin inflammation and X-ray exposure.

CSCC is the second most common cancer in the US, with approximately 700,000 cases reported a year. It is also responsible for causing 7,000 deaths annually in the US.

Libtayo’s mechanism of action

Libtayo is a recombinant human immunoglobulin G4 (IgG4) monoclonal antibody that binds to programmed death receptor-1 (PD-1), responsible for regulating T-cell response.

The drug blocks PD-1 interaction with PD-L1 and PD-L2 ligands and clears PD-1 pathway-mediated immune suppression, including the anti-tumour immune response, resulting in increased tumour surveillance and decreased tumour size.

Libtayo is available for intravenous use in the form of a sterile and opalescent solution.

Clinical trials on Libtayo

FDA approval for Libtayo comes from data of Phase II trial, EMPOWER-CSCC-1 (Study 1540) and a Phase I trial (Study 1423). A total of 108 patients enrolled in the studies, with 82 in Study 1540 and 26 in Study 1423.

Both trials were open-label, multi-centre, non-randomised, multi-cohort studies that excluded patients with autoimmune diseases and those that underwent prior treatment with anti–PD-1 / PD-L1-blocking antibodies or other immune checkpoint inhibitor therapy.

Patients were administered with 3mg/kg of Libtayo every two weeks for up to 48 weeks in Study 1423 or up to 96 weeks in Study 1540. The primary endpoint of the study was objective response rate (ORR), or the percentage of patients that experienced either partial shrinkage or complete disappearance of tumours post-treatment.

Patients administered with Libtayo showed an ORR of 47.2% with a significant reduction in tumours. The most common adverse events reported in trials were fatigue, rash and diarrhoea.

The EC’s conditional marketing authorization for Libtayo comes from results of EMPOWER-CSCC-1 study. The pivotal, open-label, multi-centre, non-randomised Phase 2 trial was complemented by two advanced CSCC expansion associates from a multi-centre, open-label, non-randomised Phase 1 trial.

Libtayo (cemiplimab) is currently under phase 3 development programme evaluation for patients with advanced non-small cell lung cancer (NSCLC).