Astex and AstraZeneca deliver ‘landmark’ breast cancer drug

A remarkable new drug hailed as a “landmark moment” in the treatment of advanced breast cancer was discovered by AstraZeneca following initial research conducted by Cambridge-based Astex Pharmaceuticals in collaboration with the Institute of Cancer Research (ICR).

The new targeted drug, capivasertib, blocks activity of the cancer-driving protein molecule AKT and has shown “fantastic” results, shrinking tumours and doubling the amount of time people have before their disease progresses.

A Phase 3 clinical trial of capivasertib alongside hormone therapy suggests the combination could become the new treatment for patients with advanced forms of the most common type of breast cancer.

The findings, presented at the San Antonio Breast Cancer Symposium on Thursday last week, relate to oestrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER-2) negative breast cancer, which accounts for around 70 per cent of all new breast cancer cases.

Capivasertib is a first-in-class inhibitor targeting AKT – important in a pathway that mediates cell division, apoptosis, and glucose and fatty acid metabolism. The new drug was discovered by pharmaceutical giant AstraZeneca following a programme of drug discovery research at the Institute of Cancer Research (ICR) in London.

The successful journey to patient use began with a programme of drug discovery research between Astex, based on Cambridge Science Park, and the ICR in London. The programme was key to understanding the potential for AKT inhibition in cancer. Subsequent to this, AstraZeneca began its own research programme which led to the discovery and development of capivasertib.

The Phase 3 trials found that capivasertib shrank tumours in 23 per cent of patients, compared with 12 per cent of patients who received fulvestrant plus a placebo.

The new drug regime was also more effective for the four in 10 patients whose cancers had mutations to the AKT signalling pathway, with 29 per cent seeing their tumours shrink compared to 10 per cent on the placebo combination.

Susan Galbraith, executive VP, oncology R&D, AstraZeneca, said: “Capivasertib brings important progress to an area with persistent treatment gaps as the first therapy of its kind shown to be effective in a Phase III trial in patients with advanced HR-positive, HER2-low or negative breast cancer. We believe these results which showed benefit in all-comers and biomarker positive populations can reshape HR-positive breast cancer treatment, and that capivasertib can become an important new option for patients.”

Astex’s work on the initial search for AKT inhibitors was based on its Pyramid discovery platform which had led to the discovery of Novartis’s Kisqali (in 2017) and Janssen’s BALVERSA (in 2019).

Pyramid, Astex’s proprietary fragment-based drug discovery platform, affords a detailed understanding of the binding environment at an atomic level, and supports a very efficient chemistry optimisation process. Drug candidates are designed to have lower molecular weight, reduced metabolic liability, improved target selectivity and ease of chemical synthesis.

Harren Jhoti, CEO of Astex, said: “We are very excited at the prospect of another drug approval from one of our academia and pharma collaborations.

“This is really good news for breast cancer patients as it potentially provides another treatment option.”

AstraZeneca is also investigating capivasertib in several other breast cancer settings as well as prostate cancer clinical studies.