Novartis' Kisqali Achieves Second Phase III Success, Becomes First CDK4/6 Inhibitor to Demonstrate Survival Benefit in Two Distinct Trials

Compiled by: Fan Dongdong

In June, Novartis presented the phase III clinical trial results of MONALEESA-7 on Kisqali for the treatment of advanced breast cancer at the ASCO 2019 annual meeting, making it the first CDK4/6 inhibitor in its class to successfully extend the survival of breast cancer patients, which has drawn widespread attention.

This study evaluated the efficacy of Kisqali combined with endocrine therapy for the treatment of advanced breast cancer in premenopausal women with hormone receptor (HR)-positive, HER2-negative disease. The results showed that the overall survival (OS) rate at 42 months was 70.2% in the Kisqali treatment group, compared to only 46.0% in the group receiving endocrine therapy plus placebo.

On July 31, Kisqali once again announced the success of its second Phase III clinical trial, known as the MONALEESA-3 study. Novartis stated that in this study, Kisqali again demonstrated a significant extension of survival time for postmenopausal patients with HR+/HER2- advanced breast cancer. The participants in this trial included women who had not previously received treatment, as well as those whose prior treatments had failed.

Kisqali is a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor that has been granted Breakthrough Therapy designation and Priority Review by the FDA.The specific details of this trial have not yet been publicly disclosed and are expected to be presented at an upcoming medical conference. Meanwhile, Novartis will also submit the trial results to global health regulatory authorities for consideration of a potential update to the indication label for Kisqali.

In 2017, the U.S. FDA approved Kisqali in combination with an aromatase inhibitor as initial endocrine therapy for the first-line treatment of postmenopausal patients with HR-positive, HER2-negative advanced or metastatic breast cancer.

The approval and market launch of Kisqali also mark the collapse of Pfizer’s monopoly in the field of CDK4/6 inhibitors. Prior to this, Pfizer’s Ibrance was the only CDK4/6 inhibitor available on the market. The drug received accelerated FDA approval in February 2015 for first-line treatment of female patients with HR+/HER2- advanced or metastatic breast cancer. In February 2016, the FDA further approved Ibrance for second-line treatment of HR+/HER2- advanced or metastatic breast cancer in patients whose disease had progressed after endocrine therapy. In July 2018, based on early progression-free survival (PFS) data from the MONALEESA-7 study, the FDA expanded this indication to include premenopausal and perimenopausal women. The median PFS was 27.5 months in the group receiving Ibrance combined with endocrine therapy, compared with 13.8 months in the placebo group. This indicates that the addition of a CDK4/6 inhibitor to endocrine therapy reduced the risk of death by 29% and the risk of disease progression by 31%.

Currently, three CDK4/6 inhibitors have been approved for marketing worldwide. The market size reached $4.608 billion in 2018, with Ibrance accounting for nearly 90% of the market share. Although Eli Lilly's Verzenio was launched six months later than Kisqali, it has demonstrated stronger market performance and its sales are now approaching those of Kisqali.

Last month, the UK’s National Institute for Health and Care Excellence (NICE) announced its recommendation supporting the use of Kisqali in combination with AstraZeneca’s Faslodex for the treatment of patients with HR+/HER2- breast cancer who have previously received other therapies. This is undoubtedly good news for Novartis, which is engaged in fierce competition with Eli Lilly and Pfizer.

The success of two Phase III clinical trials may help Kisqali gain a competitive edge over similar products, as Ibrance and Verzenio have not yet successfully completed comparable trials.

References:

1、Novartis' Kisqali sharpens survival edge with second ph3 win2、Novartis Kisqali significantly prolongs life in women with HR+/HER2- advanced breast cancer now in two distinct Phase III trials