Novartis Kisqali® (ribociclib) receives MHRA authorisation for the adjuvant treatment of HR+/HER2- early breast cancer at high risk of recurrence in a broad population of patients

• The Medicines and Healthcare products Regulatory Agency (MHRA) have authorised a new indication for ribociclib as an adjuvant treatment option to be used in combination with an aromatase inhibitor (AI) for patients with HR+/HER2- early breast cancer at high risk of recurrence. Previously this treatment option was only licenced for women diagnosed with advanced breast cancer¹.
• Despite current treatment options, people with HR+/HER2- early breast cancer remain at risk of experiencing a return of their cancer in the long term, often as incurable advanced disease^2,3.
• The MHRA decision is based on the Phase III NATALEE trial, which demonstrated that adding ribociclib to AI reduced the risk of invasive disease, recurrence, or death compared to AI alone in patients with HR+/HER2- early breast cancer^4,5.
• Broad indication secured for ribociclib increases the number of patients eligible for a CDK4/6 inhibitor⁶ in the adjuvant setting, including patient populations, who until now have had limited treatment options to reduce their risk of recurrence.

London, February 4, 2025 – Novartis UK announced today that the Medicines and Healthcare products Regulatory Agency (MHRA) have authorised a new indication for ribociclib as an adjuvant treatment option to be used in combination with an AI for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer at high risk of recurrence (see section 5.1 of the summary of product characteristics for selection criteria). In pre- or perimenopausal women, or in men, the AI should be combined with a luteinising hormone-releasing hormone (LHRH) agonist¹.

Breast cancer is the most common cancer in the UK, accounting for nearly 15% of all new cancer cases⁷, and HR+/HER2- is the most common subtype found in 70% of all breast cancers in Europe⁸. Despite current treatment options, people with HR+/HER2- eBC remain at risk of experiencing a return of their cancer in the long term, often as incurable advanced disease^2,3.

"The possibility of breast cancer returning can be a continuous concern for people who have been diagnosed with the disease. Therefore, providing an additional layer of protection to a broad population of patients at high risk of recurrence is always reassuring." said Stephen Johnston, Professor of Breast Cancer Medicine, Consultant Medical Oncologist, and Head of the Breast Unit at the Royal Marsden NHS Foundation Trust. "The introduction of ribociclib as a treatment option for early-stage breast cancer to reduce the risk of recurrence is a promising development for both clinicians and patients, including those with node-negative disease and additional risk factors." 

The approval is based on results from the Phase III NATALEE trial, which included pre-/postmenopausal women and men with HR+/HER2- with any lymph node involvement (excluding microscopic nodal involvement), or if no nodal involvement either tumour size >5 cm, or tumour size 2-5 cm with either grade 2 (and high genomic risk or Ki67 ≥20%) or grade 3. The trial showed a significant and clinically meaningful 25.1% (HR 0.749, 95% CI 0.628-0.892; p = 0.0012) reduction in invasive disease-free survival (IDFS) events versus using aromatase inhibitor alone. iDFS at 3 years was 90.7% (95% CI 89.3%-91.8%) versus 87.6% (95% CI 86.1%-88.9%) respectively (absolute reduction: 3.1%)^1,4,5.

There were no new safety signals reported in the final analysis of the NATALEE trial. The most common adverse drug reactions (ADRs) (reported at a frequency ≥20%) in the dataset for which the frequency for ribociclib plus aromatase inhibitor (AI) exceeds the frequency for AI alone were neutropenia, infections, nausea, headache, fatigue, leukopenia and abnormal liver function tests. The most common grade 3/4 ADRs (reported at a frequency of ≥2%) in the dataset for which the frequency for ribociclib plus AI exceeds the frequency for AI alone were neutropenia, abnormal liver function tests and leukopenia^4,5.

With the most recent analysis of the NATALEE trial data announced at ESMO, Novartis continues to evaluate NATALEE patients for longer-term outcomes, including overall survival¹⁰.

“The announcement reinforces Novartis' 30-year legacy in driving scientific advancements for people affected by breast cancer. With consistent results across patient subgroups, ribociclib is now licenced for a broad population of patients diagnosed with HR+/HER2- eBC at high risk of recurrence,” said Gerrit Zijlstra, Chief Medical Officer for the UK & Ireland at Novartis. “The MHRA decision builds on the confidence established by the NATALEE trial and highlights the potential of ribociclib to reduce the risk of recurrence in eBC, addressing a significant unmet need for patients in the UK.”

The MHRA licence in the UK comes shortly after the European Medicines Agency (EMA) approval for ribociclib across Europe. Following MHRA authorisation, the National Institute for Health and Care Excellence (NICE) and Scottish Medicines Consortium (SMC) submissions are under review to secure reimbursement of ribociclib to increase patient access via the National Health Service (NHS). 

About NATALEE

NATALEE is a global Phase III multi-center, randomised, open-label trial to evaluate the efficacy and safety profile of ribociclib with AI as an investigational adjuvant treatment versus AI alone, in patients with stage II and III HR+/HER2- eBC, being conducted in collaboration with TRIO^4,7. Pre-/perimenopausal women and men in both groups were also treated with an LHRH agonist. The adjuvant AI in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable^4,7. The primary endpoint of NATALEE is invasive disease-free survival (iDFS) as defined by the Standardised Definitions for Efficacy End Points (STEEP) criteria^4,7. A total of 5,101 adult patients with HR+/HER2- eBC across 20 countries were randomised in the trial^1,4,7. 

About ribociclib

Ribociclib is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably¹.

In the UK, ribociclib is currently licenced in combination with an aromatase inhibitor (AI) or fulvestrant as initial endocrine based therapy, or in women who have received prior endocrine therapy. In pre- or perimenopausal women, the endocrine therapy should be combined with an LHRH agonist¹. The treatment is available on the NHS for eligible women with a type of breast cancer called hormone receptor-positive (HR+) and human epidermal growth factor receptor (HER2)-negative breast cancer that is either locally advanced or metastatic. This means the cancer has grown outside the breast and spread to the lymph nodes of the breast (locally advanced) or has spread to other parts of the body (metastatic). 

About Novartis

Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. 

In the UK, we champion health and lives through pioneering NHS partnerships, innovative collaborations and a clear focus on the greatest healthcare challenges we all face. We are where science meets hope.

To reimagine medicine with us, visit our website at https://www.novartis.com/uk-en/ and connect on LinkedIn, Facebook, and Instagram.