* Medicines & Healthcare products Regulatory Agency Decision ABROCITINIB: PUBLIC ASSESSMENT REPORT Published 2 February 2021 THIS DECISION WAS WITHDRAWN ON 5 MAY 2022 Granting of

marketing authorisation CONTENTS * 1. Early Access to Medicines Scientific Opinion - Public Assessment Report * 2. Company * 3. Introduction Print this page © Crown copyright 2021 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: [email protected].

PUBLIC ASSESSMENT REPORT 1.1 PRODUCT Abrocitinib 100 mg Tablets 1.2 EAMS INDICATION Abrocitinib is indicated for the treatment of adult and adolescent patients with severe atopic dermatitis

requiring treatment with systemic therapy and have had inadequate response or have lost response to approved systemic therapies, or those who are ineligible or intolerant of approved

systemic therapies 2. COMPANY Pfizer Limited 2.1 EAMS NUMBER EAMS 00057/006 2.2 EAMS SCIENTIFIC OPINION DATE 28/01/2021 3. 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 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 3.1 WHAT IS

ABROCITINIB? Abrocitinib is an active substance of a medicine given orally in the form of 100 mg tablets. 3.2 WHAT IS ABROCITINIB USED TO TREAT? Abrocitinib is used to treat adult and

adolescent patients with severe atopic eczema (also called atopic dermatitis) who have not responded to the approved treatments available to them or who are ineligible or intolerant to the

approved treatments. 3.3 HOW IS ABROCITINIB USED? Abrocitinib can only be prescribed by physicians experienced in the treatment of severe atopic dermatitis (AD). Abrocitinib should be taken

as one (100 mg) or two tablets (200 mg) along with water, with or without food at approximately the same time each day. In patients who experience nausea while taking abrocitinib, taking

with food may improve nausea. Dose will be selected by the doctor based on the individual goal of therapy and risk factors for adverse events. Most patients in the EAMS setting will require

treatment with a dose of 200 mg, however some patients who have risk factors for developing an adverse reaction to abrocitinib or who are less likely to tolerate an adverse reaction, a dose

of 100 mg should be considered. The dose may be reduced if a patient has kidney problems or if they are prescribed certain other medications. Abrocitinib can be used with or without other

topical treatments for AD (treatment directly applied to skin, for example, steroid creams). The doctor will carry out blood tests before and during treatment to monitor the patient.

Abrocitinib may cause a decrease in the platelet or lymphocyte count or an increase in the lipid parameters. Abrocitinib can also cause certain side effects like serious infections due to

its effect on the immune system. If these side effects occur, abrocitinib treatment may be interrupted or permanently discontinued, depending on the severity of the side effect. 3.4 HOW DOES

ABROCITINIB WORK? Abrocitinib acts by reducing the activity of the immune system. It works by blocking the action of an enzyme known as Janus kinase 1. This enzyme plays an important role

in the process of skin inflammation that occurs in atopic dermatitis. Patients have an overactive inflammatory response in the skin and abrocitinib works by dampening this down. 3.5 HOW HAS

ABROCITINIB BEEN STUDIED? Abrocitinib has been studied in clinical trials of more than 2500 patients (including more than 350 adolescent patients) with moderate to severe atopic dermatitis.

The main studies compared abrocitinib alone or with topical therapies with a placebo drug. Patients who had a severe disease and had not responded adequately to other available treatment

options were also included in the clinical studies. 3.6 WHEN SHOULD ABROCITINIB NOT BE GIVEN? Abrocitinib should not be given to patients if they are pregnant. Female patients should use an

effective method of contraception to avoid becoming pregnant during treatment with abrocitinib. Abrocitinib should not be given to patients if their blood test shows a low count of

platelets, neutrophils or lymphocytes or a low haemoglobin level. 3.7 WHAT ARE THE BENEFITS AND RISKS OF ABROCITINIB? BENEFITS Abrocitinib showed a clinically meaningful reduction in the

severity of eczema lesions as well as reducing their extent (how much of the body’s surface is affected) in comparison to placebo in patients with moderate or severe AD. In two studies,

40-45% of patients given abrocitinib 100 mg and 61-63% of those given 200 mg had a meaningful reduction in EASI score (an assessment score which reflects the severity and extent of the

disease in AD) compared to 10-12% of those given placebo, after 12 weeks of treatment. In the same studies, 24-28% of patients given abrocitinib 100 mg and 38-44% of those given 200 mg had a

skin clear or almost clear of inflammation compared with 8-9% of those who were given placebo. In another study in which abrocitinib or placebo were added to topical treatments, the

percentage of patients who showed a meaningful reduction in EASI score were 59%, 70% and 27% with abrocitinib 100 mg, abrocitinib 200 mg and placebo, respectively. The percentage of patients

who showed a skin clear or almost clear of inflammation were 37%, 48% and 14% with abrocitinib 100 mg, abrocitinib 200 mg and placebo, respectively. Patients treated with abrocitinib also

experienced a reduction in itching and an improvement in sleep and quality of life. The results in subgroup of patients with severe AD showed broadly similar benefits. RISKS The most common

side effects with abrocitinib are nausea, cold sores (herpes simplex), vomiting, upper abdominal pain, headache, dizziness, acne and an increase in blood levels of creatinine phosphokinase.

As abrocitinib acts on body’s immune system, few patients may have infections such as painful skin rash with blisters (shingles), or a rapidly spreading painful rash, blisters or sores (with

or without fever) known as eczema herpeticum. Abrocitinib may also cause some uncommon but serious side effects like serious infections and blood clots in the lungs, legs or pelvis.

Abrocitinib may cause a decrease in the platelet or lymphocyte count or an increase in the lipid levels in the blood. Depending on the severity of the side effect, abrocitinib treatment may

be interrupted or permanently discontinued. 3.8 WHY HAS ABROCITINIB BEEN GIVEN A POSITIVE EARLY ACCESS TO MEDICINE SCIENTIFIC OPINION? Severe atopic eczema is a seriously debilitating

disease that has a major impact on quality of life and the treatment options available are limited, can have harmful effects or may not achieve an adequate response. Under EAMS, abrocitinib

is being made available to those patients with the highest need - those who have a severe disease and who have run out of treatment options. Abrocitinib results in meaningful improvement in

the extent and severity of eczema as well as in itch and in some patients the improvement may be marked. The risks associated with abrocitinib can be managed and do not outweigh the

benefits. 3.9 WHAT ARE THE UNCERTAINTIES? The long-term risks of abrocitinib are not known. There is no or limited data for abrocitinib in pregnant or breast-feeding women. Abrocitinib

should not be used in women who are pregnant or during breast-feeding. There is no clinical data at present on the benefits and risks of abrocitinib in patients under the age of 12 years.

Further information is needed to understand how the use of two doses of abrocitinib could be optimised depending on the treatment response and occurrence of side effects to manage the

disease more effectively. The company that makes abrocitinib will provide additional information when it becomes available. 3.10 ARE THERE ON-GOING CLINICAL STUDIES? Studies with abrocitinib

are ongoing in adult patients to understand the effect of dose modification and discontinuation in patients with moderate or severe AD, and to collect further safety data after long term

treatment with abrocitinib. A study comparing abrocitinib or placebo in addition to topical treatments in adolescent patients is also ongoing. 3.11 WHAT MEASURES ARE IN PLACE TO MONITOR AND

MANAGE RISKS? A risk management plan has been developed to ensure that abrocitinib is used as safely as possible. Based on this plan, the company that makes abrocitinib must ensure that all

healthcare professionals expected to use the medicine, as well as patients, are provided with information on the medicines 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 abrocitinib through the scheme. To assist with this, they will receive a physician pack and training prior to commencement of patient treatment. These 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 a patient alert card from their doctor summarising the important

risks with abrocitinib treatment and details of their treating physician. Patients should carry the alert card with them at all times in case they need treatment or advice from a healthcare

professional who is not familiar with abrocitinib treatment. Other information about pemigatinib – see EAMS Treatment Protocol Back to top