OSIMETRINIB AND NECITUMUMAB NEAR APPROVAL FROM EMA

Two novel products for the treatment of non-small-cell lung cancer (NSCLC) have been recommended for approval in Europe: osimertinib (Tagrisso, AstraZeneca) and necitumumab (Portrazza, Eli Lilly).

Osimertinib Was Fast-Tracked

Osimertinib has been fast-tracked through the bureaucratic process. The European Medicines Agency's (EMA) recommendation to grant a conditional marketing authorization comes after the Committee for Medicinal Products for Human Use (CHMP) reviewed the product under the EMA's accelerated assessment program. Conditional approval allows EMA to recommend a medicine for marketing authorization before the availability of confirmatory clinical trial data, if the benefits outweigh any risks related to the lack of comprehensive data.

In this case, the conditional approval is based on response-rate data from single-group studies. Thus, the manufacturer must eventually provide further data from an ongoing phase 3 study.

Osimertinib is intended for a particular group of NSCLC patients — those with a specific mutation (T790M) of the epidermal growth-factor receptor (EGFR). Once patients develop this mutation, they no longer respond to treatment with EGFR inhibitors, such as erlotinib (Tarceva), and related agents. The EMA says that safety and efficacy of osimertinib were demonstrated in two single-group phase 2 trials involving a total of 411 patients with advanced EGFR T790M mutation-positive NSCLC whose disease progressed after treatment with an EGFR inhibitor.

Osimertinib was approved in the United States in November on the strength of these same data. Results from these two trials showed that a high proportion of patients (around 66%) responded and their tumors shrank. This response appeared to be long-lasting. Data on progression-free survival and/or overall survival have not yet been determined.

The most common adverse effects of osimertinib are diarrhea and skin and nail conditions, such as dry skin, rash, and acne.

Necitumumab Also for EGFR-Positive NSCLC

The other product, necitumumab, has been recommended for a full marketing approval after a positive opinion from the CHMP. This product has shown a modest survival benefit and is approved in the United States.

Necitumumab is also intended for use in patients with EGFR-positive NSCLC, specifically in patients who have not received prior chemotherapy. It is used with gemcitabine and cisplatin, and has shown an "ability to improve survival compared with chemotherapy alone," the EMA notes.

The most common adverse effects are skin reactions, venous thromboembolic events, and the laboratory abnormalities of hypomagnesaemia and albumin-corrected hypocalcaemia.

Necitumumab is a recombinant human IgG1 monoclonal antibody that binds with high affinity and specificity to the human EGFR and blocks the ligand binding site, the agency explains.