AstraZeneca upbeat on positive developments for Imfinzi and Lynparza

AstraZeneca and its global biologics research and development arm MedImmune announced on Monday that the Japanese Ministry of Health, Labour and Welfare has approved Imfinzi (durvalumab) as maintenance therapy after definitive chemoradiation therapy (CRT) in locally-advanced, unresectable non-small cell lung cancer (NSCLC).

The FTSE 100 drugmaker said the approval of Imfinzi was based on positive progression-free survival (PFS) data from the Phase III PACIFIC trial in unresectable Stage III NSCLC.

In the trial, Imfinzi demonstrated an improvement in median PFS of 11.2 months compared to placebo.

Imfinzi improved other meaningful outcomes such as time to distant metastasis or death and overall response rates, it added.

The incidence and severity of adverse events was said to be “comparable” for patients receiving Imfinzi, compared to patients receiving placebo.

AstraZeneca said the most frequent adverse reactions were rash which occurred in 73 subjects, hypothyroidism which occurred in 50 subjects, diarrhoea which occurred in 46 subjects, and interstitial lung disease which occurred in 46 subjects.

In May, AstraZeneca announced that the PACIFIC trial had met its second primary endpoint, showing “statistically-significant and clinically-meaningful” overall survival in patients receiving Imfinzi compared to placebo.

Full results would be presented at a forthcoming medical meeting, the company confirmed.

Imfinzi was also approved in the US, Canada, Switzerland and India based on the Phase III PACIFIC trial.

Regulatory reviews in the EU and other jurisdictions were ongoing, with an EU decision expected in the second half of 2018.

“Non-small cell lung cancer is a leading cause of death in Japan, and we are dedicated to bringing new treatment options to patients as quickly as possible,” said AstraZeneca’s executive vice-president and head of the oncology business Dave Fredrickson.

“As the only immunotherapy approved in the curative-intent, Stage III lung cancer setting, Imfinzi has the potential to change the treatment paradigm for patients diagnosed with this disease.”

In a separate announcement, AstraZeneca and its partner Merck announced that Japan's Pharmaceuticals and Medical Devices Agency (PMDA) has approved Lynparza (olaparib) tablets for use in patients with unresectable or recurrent BRCA-mutated (BRCAm), human epidermal growth factor receptor 2 (HER2) negative breast cancer who have received prior chemotherapy.

The firm said patients were selected for therapy based on an approved companion diagnostic.

“Earlier this year, Lynparza became the first PARP inhibitor available in Japan for advanced ovarian cancer,” Dave Fredrickson said of that development.

“Now patients in Japan with BRCA-mutated, metastatic breast cancer will also have the opportunity to benefit from Lynparza.

“This latest approval underlines our ongoing efforts to make Lynparza available across multiple cancers as quickly as possible to patients around the world.”

The approval was based on data from the randomised, open-label, Phase III OlympiAD trial, which tested Lynparza against chemotherapy.

Patients were selected for therapy based upon a confirmed BRCA mutation.

In the trial, Lynparza reportedly significantly prolonged progression-free survival compared with chemotherapy, reducing the risk of disease progression or death by 42%.

Lynparza was “generally well tolerated”, with the majority of adverse events reported as mild to moderate with a lower rate of Grade 3 or higher AEs compared with chemotherapy.

AstraZeneca said the most common adverse effects were nausea at 50.2%, anaemia at 32.2%, and fatigue at 22.4%.

Lynparza was also approved in Japan as maintenance treatment for women with platinum-sensitive relapsed ovarian cancer, regardless of BRCA mutation status.

In Japan, the co-promotion of Lynparza by both companies was beginning on 1 July

“Metastatic breast cancer is a complex disease with remaining unmet medical need,” said Roy Baynes, senior vice-president and head of global clinical development, and chief medical officer at Merck’s MSD Research Laboratories.

“This approval is significant for breast cancer patients as the evaluation of BRCA mutations, in addition to hormone receptor and HER2 status, now becomes an important step in the management of the disease.”