CHMP issues positive recommendations for nine new medicines, including Tagrisso in treatment of NSCLC

The European Medicine Agency's (EMA) Committee for Medicinal Product for Human Use (CHMP) published recommendation for the approval of nine new medicinal products on 18 December. The CHMP also issued six recommendations for indication extensions. The full text is available here.

The most significant recommendation was AstraZeneca's Tagrisso (formerly AZD9291), which received a fast-tracked conditional market-authorisation recommendation as a treatment option for locally advanced or metastatic EGFR T790M mutation-positive NSCLC. Conditional market-authorisation recommendations are granted to products for unmet medical needs where the benefit to public health of immediate availability is deemed to outweigh the requirement of gathering additional clinical-trial data. AstraZeneca will be obliged to provide comprehensive clinical data post-market authorisation. In the meantime, the EMA will reassess the safety and efficacy of Tagrisso on an annual basis.

The approval was based on two Phase II trials (AURA extension and AURA2) investigating the safety and efficacy of Tagrisso in 474 patients with EGFR T790M mutation-positive NSCLC, whose disease had progressed after treatment with EGFR-blocking therapies. These trials demonstrated that the objective response rate was 66% and 61% respectively, and that the response was long-lasting. Data for progression-free survival and overall survival rates have not yet been determined. An open label, randomised Phase III study (AURA3) is currently being conducted to assess the efficacy and safety of Tagrisso versus platinum-based doublet chemotherapy in patients with EGFR T790M positive, locally advanced, or metastatic NSCLC, who have progressed following prior therapy with an EGFR-TK.

Assuming the third-generation EGFR inhibitor is eventually granted final market-authorisation approval by the European Commission – probably in the first quarter of 2016 – Tagrisso would be the sole European-approved medicine indicated for patients with metastatic EGFR T790M mutation-positive NSCLC. The EMA's recommendation to approve the 80mg once-daily tablets was based on tumour-response rates and duration of response. Tagrisso's principal commercial rival is likely to be Clovis Oncology (US)'s experimental NSCLC treatment, rociletinib, which has been accepted for review by the EMA but remains several months away from potential commercialisation (see Europe - United States: 2 October 2015: Clovis NSCLC candidate to benefit from expedited reviews in US and Europe). The EMA could potentially issue a decision on rociletinib's market-authorisation application by mid-2016. Similarly, European market authorisation for Tagrisso would give AstraZeneca a significant commercial advantage, allowing the company to consolidate its market position ahead of another rival third-generation EGFR inhibitor – BI 1482694 (Boehringer Ingelheim, Germany) – which recently achieved a US FDA breakthrough-therapy designation, based on Phase I/II clinical trials (HM-EMSI-101). AstraZeneca has not disclosed its planned pricing strategy for Tagrisso in Europe. However, the company previously signalled that the treatment would be priced comparably to "other oral-cancer therapies". In November, AstraZeneca also announced that the cost per patient, per year in the US market for Tagrisso would be about USD150,000 (equivalent to USD12,750 per month, per patient); this price is likely to be reduced significantly for the European region.

Outlook and implications

The conditional approval for Tagrisso is considered a significant development, as it will facilitate early access to the innovative medicine for those European patients with limited treatment options and decreased life expectancy, prior to the availability of confirmatory clinical-trial results. The agency's decision to recommend conditional market-authorisation access – based on the principle that the benefits of the promising medication were greater than the risk – will be broadly welcomed by the pharmaceutical sector. Elsewhere, the latest recommendations bring the number of positive opinions for new-medicine approvals by the EMA to 93 in 2015, compared with 82 approvals for 2014 as a whole. Another significant EMA recommendation was for Portrazza (necitumumab; Eli Lilly, US), in combination with gemcitabine and cisplatin, to treat chemotherapy-naive adult patients with locally advanced or metastatic EGFR squamous NSCLC. The recommended approval was based on Phase III clinical data (SQUIRE), which compared treatment with Portrazza in combination with gemcitabine and cisplatin to treatment with gemcitabine and cisplatin alone. The Portrazza arm of the study reached its primary endpoint by demonstrating a statistically significant improvement in median overall survival (11.5 months compared to 9.9 months for those treated with gemcitabine and cisplatin alone). No information on the price of Portrazza in Europe has been released; however, the US price of the treatment is approximately USD11,430 for a 30-day regimen. The European Commission is expected to announce a decision on granting final market-authorisation approval within two months of the publication of the CHMP opinion. The commission's decision will be applicable across the 28 countries of the European Union, in addition to Norway, Iceland, and Liechtenstein.