Asciminib Public Assessment Report (PAR)
Updated 13 December 2022
© Crown copyright 2022
This publication is licensed under the terms of the Open Government Licence v3.0 except where otherwise stated. To view this licence, visit nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: psi@nationalarchives.gov.uk.
Where we have identified any third party copyright information you will need to obtain permission from the copyright holders concerned.
This publication is available at https://www.gov.uk/government/publications/asciminib-in-the-treatment-of-chronic-myeloid-leukaemia/asciminib-public-assessment-report-par
Early Access to Medicines Scientific Opinion - Public Assessment Report
Product
Asciminib
EAMS indication
Treatment of adult patients with a blood cancer called Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase that does not have a gene defect (T315I mutation) and who have previously received treatment with at least two medicines named tyrosine kinase inhibitors.
Company
Novartis Pharmaceuticals UK Limited
EAMS number
00101/0006
EAMS Scientific Opinion date
11 January 2022
Introduction
The aim of the Early Access to Medicines Scheme (EAMS) is to provide earlier availability of promising new unlicensed medicines and medicines used outside their licence, to UK patients that have a high unmet clinical need. The MHRA scientific opinion provides benefit and risk information to physicians who may wish to prescribe the EAMS medicine under their own responsibility. More information about the scheme can be found here: http://www.mhra.gov.uk/Howweregulate/Innovation/EarlyaccesstomedicinesschemeEAMS/index.htm
The scientific opinion is based on assessment of the information supplied to the MHRA on the benefits and risks of the medicine. As such this is a scientific opinion and should not be regarded as a medicine licensed by the MHRA or a future commitment by the MHRA to license such a medicine, nor should it be regarded as an authorisation to sell or supply such a medicine. A positive scientific opinion is not a recommendation for use of the medicine and should not be interpreted as such. Under EAMS the risk and legal responsibility for prescribing a ‘special’ remains with the physician, and the opinion and EAMS documentation published by the MHRA are intended only to inform physicians’ decision making and not to recommend use. An EAMS scientific opinion does not affect the civil liability of the manufacturer or any physician in relation to the product
The General Medical Council’s guidance on prescribing unlicensed medicines can be found here: https://www.gmc-uk.org/guidance/ethical_guidance/14327.asp
What is asciminib?
Asciminib is the active substance of a medicine, which is taken orally in the form of 20 mg or 40 mg tablets.
What is asciminib used to treat?
Asciminib is used to treat adults with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase that do not have a gene defect called T315I mutation and who are no longer benefiting from the previous treatment of at least two medicines called tyrosine kinase inhibitors.
Chronic myeloid leukaemia is a type of blood cancer in which the body produces too many abnormal white blood cells. Chronic phase is the first phase of this blood cancer.
How is asciminib used?
Asciminib can only be prescribed by a doctor experienced in the treatment of chronic myeloid leukaemia.
Asciminib is taken orally without food. Food consumption should be avoided for at least 2 hours before and 1 hour after taking asciminib. The tablets should be swallowed whole and should not be broken, crushed or chewed.
Asciminib is taken at a total daily dose of 80 mg. It can be taken either as 40 mg twice daily (at approximately 12 hours apart) or as 80 mg once a day (at approximately the same time each day). This treatment continues until there is no longer any benefit from it, or it is no longer tolerated.
The dose is not adjusted in older patients (at least 65 years of age), patients with kidney problems and patients with liver problems. There is not enough evidence to recommend the use of asciminib in children and adolescents below the age of 18 years.
The doctor will carry out tests before and during treatment to monitor the patient’s functions.
Asciminib can cause certain side effects. If these side effects occur, treatment may be interrupted or the dose reduced or permanently discontinued, depending on the severity of the side effect.
How does asciminib work?
Asciminib blocks the action of a protein (BCR-ABL1 tyrosine kinase) produced by the cancer cells and stops their division and growth. Asciminib has been designed to target a specific part of the tyrosine kinase called the ABL myristoyl pocket.
How has asciminib been studied?
A total of 233 adult patients with chronic myeloid leukaemia in chronic phase were enrolled into a study that compared asciminib with another drug used in the treatment of this cancer called bosutinib. The study patients had received previously at least two other treatments using medicines called tyrosine kinase inhibitors. The study excluded patients that had the disease with the gene defect T315I mutation.
Two thirds of the study patients received asciminib and one third received bosutinib. Study treatment was decided randomly by a central computer. The patients were followed-up with regular visits and monitored for side effects. Patients continued treatment until unacceptable toxicity or the treatment was no longer working. Asciminib treatment was continued for an average of 67 weeks (maximum of 162 weeks).
The main measure of efficacy (how well the medicine worked) was major molecular response rate. The molecular response indicates whether the abnormal BCR-ABL1 gene is present, using a very sensitive molecular test.
What are the benefits and risks of asciminib?
Benefits
The study showed that at 24 weeks of having received the treatment, the proportion of patients with a molecular response was 25.48% in the group of patients treated with asciminib compared to 13.16% in those treated with bosutinib.
Risks
The most common side effects affecting at least 20% of patients receiving asciminib are muscle or bone pain, upper respiratory tract infections (affecting nose, sinuses or pharynx) , low platelets in the blood (cells that fight bleeding), fatigue (tiredness), headache, abnormal tests of the pancreas, pain in the joints and nausea (feeling sick).
Serious side effects have been reported in 12.4% of patients receiving asciminib. The most frequent serious side effects were pleural effusion (fluid collection between the lungs and chest cavity), lower respiratory tract infections (like pneumonia or bronchitis), low platelets in the blood, fever, inflammation of the pancreas, chest pain that is not related to the heart, and vomiting (being sick).
Depending on the severity of the side effect, asciminib treatment may be interrupted, the dose reduced or permanently discontinued.
Why has asciminib been given a positive Early Access to Medicine Scientific opinion?
There are a limited number of medicines available for patients that have received treatment with at least two tyrosine kinase inhibitors and still need treatment for the cancer. The available medicines have either significant toxicity or are reported to be less active against the cancer in patients who have already received several treatments. Asciminib has been shown to be notably active against the cancer compared to current treatment with bosutinib. The risks associated with asciminib can be managed and do not outweigh the benefits.
What are the uncertainties?
Long term efficacy data has not been determined (e.g. data on how long patients live or how long patients live without their cancer getting worse).
Information is missing regarding the side effects in patients who take asciminib long term. There is no clinical data at present on the benefits and risks of asciminib in patients under the age of 18 years.
The company that makes asciminib will provide additional information when it becomes available.
Are there on-going clinical studies?
The study previously described comparing asciminib with bosutinib is ongoing to fully understand the effect of asciminib against the cancer in the long term and to collect further safety data after long term treatment with asciminib.
What measures are in place to monitor and manage risks?
A risk management plan has been developed to ensure that asciminib is used as safely as possible. Based on this plan, the company that make asciminib must ensure that all healthcare professionals expected to use the medicine, as well as patients, are provided with information on the medicine including the side effects and recommendations for minimising these side effects.
Information will be collected about patients before they enter the scheme. Healthcare professionals will be asked by the company to report side effects experienced by patients receiving asciminib through the scheme. They will receive comprehensive training prior to commencement of patient treatment. Safety data will be reviewed and reported to the MHRA on a regular basis by the company.
Patients in the Early Access to Medicines Scheme will receive an alert card from their doctor summarising the serious side effects of the medicines and the details of their treating oncologist. Patients should carry the cards with them at all times in case they need treatment or advice from a healthcare professional who is not familiar with asciminib treatment.
Other information about asciminib – see EAMS Treatment Protocol