Selumetinib granted US Breakthrough Therapy Designation in neurofibromatosis type 1

AstraZenecaAstraZeneca and MSD, Inc., Kenilworth, NJ, US (MSD: known as Merck & Co., Inc. inside the US and Canada) today announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for the MEK 1/2 inhibitor and potential new medicine selumetinib.

This designation is for the treatment of paediatric patients aged three years and older with neurofibromatosis type 1 (NF1) symptomatic and/or progressive, inoperable plexiform neurofibromas (PN), a rare, incurable genetic condition.

José Baselga, Executive Vice President, Research and Development, Oncology, said: "Selumetinib shows promise in the treatment of NF1-related plexiform neurofibromas, a rare and debilitating disease with no approved medications to date. The Breakthrough Therapy Designation acknowledges the significant unmet need of these patients and the potential benefit of selumetinib in this setting."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, at MSD Research Laboratories, said: "This new designation validates our ongoing development of selumetinib. As a result of this, selumetinib has the potential to receive expedited regulatory review and we hope to bring this medicine to patients as soon as possible."

The BTD is based on Phase II data from the SPRINT trial, testing selumetinib as an oral monotherapy in paediatric patients, aged three years or older with inoperable NF1-related PN. The results of the trial were presented by the National Cancer Institute (NCI) at the 2018 American Society of Clinical Oncology Annual Meeting.

This is the ninth BTD that AstraZeneca has received from the FDA since 2014. BTD is designed to expedite the development and regulatory review of medicines that are intended to treat a serious condition and that have shown encouraging early clinical results, which may demonstrate substantial improvement on a clinically-significant endpoint over available medicines.

Selumetinib was granted Orphan Drug Designation for the treatment of NF1 by the US FDA in February 2018 and the European Medicines Agency in August 2018.

Selumetinib is a MEK 1/2 inhibitor and potential new medicine licensed by AstraZeneca from Array BioPharma Inc. in 2003. AstraZeneca and MSD entered a co-development and co-commercialisation agreement for selumetinib in 2017.

The NF1 gene provides instructions for making a protein called neurofibromin, which negatively regulates the RAS/MAPK pathway, helping to control cell growth, differentiation and survival. Mutations in the NF1 gene may result in dysregulations in RAS/RAF/MEK/ERK signalling, which can cause cells to grow, divide and copy themselves in an uncontrolled manner, and may result in tumour growth. Selumetinib inhibits the MEK enzyme in this pathway, potentially leading to inhibition of tumour growth.

Selumetinib is being assessed as a monotherapy and in combination with other treatments in ongoing trials.

About SPRINT

The SPRINT trial is a US Cancer Therapy Evaluation Program (CTEP) NCI-sponsored Phase I/II trial. The Phase I trial was designed to identify the optimal Phase II dosing regimen, and the results were published in the New England Journal of Medicine.(1)

About NF1

Neurofibromatosis type 1 (NF1) is an incurable genetic condition that affects one in 3,000 to 4,000 individuals.(2,3) It is caused by a spontaneous or inherited mutation in the NF1 gene and is associated with many symptoms, including soft lumps on and under the skin (cutaneous neurofibromas), skin pigmentation (so-called 'cafe au lait' spots) and, in 20-50% of patients, tumours develop on the nerve sheaths (plexiform neurofibromas). These plexiform neurofibromas can cause clinical issues such as pain, motor dysfunction, airway dysfunction, bowel/bladder dysfunction and disfigurement as well as having the potential to transform into malignant peripheral nerve sheath tumours (MPNST).

People with NF1 may experience a number of complications such as learning difficulties, visual impairment, twisting and curvature of the spine, high blood pressure, and epilepsy. NF1 also increases a person’s risk of developing other cancers, including malignant brain tumours, MPNST and leukaemia. Symptoms begin during early childhood, with varying degrees of severity, and can reduce life expectancy by up to 15 years.(4)

About the AstraZeneca and MSD Strategic Oncology Collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza (olaparib), the world’s first PARP inhibitor and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca's five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms - Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates - and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.

1. Dombi E, et al. Activity of Selumetinib in Neurofibromatosis Type 1–Related Plexiform Neurofibromas. N Engl J Med. 2016; 375:2550-2560.
2. NHS Choices. Neurofibromatosis Type 1. Available at https://www.nhs.uk/conditions/neurofibromatosis-type-1/. Accessed March 2019.
3. Johnson KJ, et al. Development of an International Internet-based Neurofibromatosis Type 1 Patient Registry. Contemporary Clinical Trials. 2013;34:305-311.
4. Evans DGR, et al. Reduced Life Expectancy Seen in Hereditary Diseases Which Predispose to Early-Onset Tumors. Appl Clin Genet. 2013; 6:53-61

Most Popular Now

Roche's COVID-19 antibody test receives FDA Emerge…

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced that the U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) (1) for its new Elecsys® Ant...

Pfizer and BioNTech dose first participants in the…

Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) announced that the first participants have been dosed in the U.S. in the Phase 1/2 clinical trial for the BNT162 va...

Johnson & Johnson announces collaboration to e…

Johnson & Johnson (the Company) (NYSE: JNJ) announced a collaboration between the Janssen Pharmaceutical Companies of Johnson & Johnson and Emergent BioSolutions, Inc. to...

Researchers urge clinical trial of blood pressure …

Researchers in the Ludwig Center at the Johns Hopkins Kimmel Cancer Center report they have identified a drug treatment that could - if given early enough - potentially r...

Early indicators of vaccine efficacy

Ludwig-Maximilians-Universität (LMU) in Munich researchers have shown that a specific class of immune cells in the blood induced by vaccination is an earlier indicator of...

Official COVID-19 deaths underestimate the full im…

According to a study by Charité - Universitätsmedizin Berlin, the northern Italian city of Nembro recorded more deaths during March 2020 than between January and December...

Arthritis drug may improve respiratory function in…

A small study in Greece found that the clinically approved anti-inflammatory drug anakinra, used to treat rheumatoid arthritis, improved respiratory function in patients ...

Local climate unlikely to drive the early COVID-19…

Local variations in climate are not likely to dominate the first wave of the COVID-19 pandemic, according to a Princeton University study published May 18 in the journal ...

Frankfurt researchers discover potential targets f…

A team of biochemists and virologists at Goethe University and the Frankfurt University Hospital were able to observe how human cells change upon infection with SARS-CoV-...

AstraZeneca advances response to global COVID-19 c…

AstraZeneca is advancing its ongoing response to address the unprecedented challenges of COVID-19, collaborating with a number of countries and multilateral organisations...

Antibody neutralizes SARS and COVID-19 coronavirus…

An antibody first identified in a blood sample from a patient who recovered from Severe Acute Respiratory Syndrome in 2003 inhibits related coronaviruses, including the c...

Vitamin D linked to low virus death rate

A new study has found an association between low average levels of vitamin D and high numbers of COVID-19 cases and mortality rates across 20 European countries. The r...