Decision

tepotinib: Treatment protocol: Information on the Pharmacovigilance System

Published 13 July 2021

This decision was withdrawn on 7 October 2021

Granting of marketing authorisation

Early Access to Medicines Scheme – Treatment protocol – Information on the pharmacovigilance system and requirements for reporting safety data

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 medicinal products included in the scheme are those that are intended to treat, diagnose or prevent seriously debilitating or life-threatening conditions where there are no adequate treatment options.

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 licensed indication or a future commitment by the MHRA to licence 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 the medicine 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.

As the safety profile of the EAMS medicine may not yet be fully established, it is particularly important that any harmful or unintended responses to EAMS medicines are reported. More information about the scheme can be found here: http://www.mhra.gov.uk/Howweregulate/Innovation/EarlyaccesstomedicinesschemeEAMS/index.htm

Physicians should enroll any patients receiving EAMS medicines in the drug registry put in place by the pharmaceutical company to enable systematic collection of information on adverse events. Suspected adverse drug reactions (ADRs) for any patients can also be reported directly to the MHRA via the Yellow card scheme at <www.mhra.gov.uk/yellowcard>. When reporting, please provide as much information as possible, including information about medical history, any concomitant medication, onset, treatment dates, outcome and results of any test results or investigations.

The information below is intended for healthcare professionals and is provided by the pharmaceutical company that manufactures the EAMS medicine. It summarises the requirements for clinical monitoring and reporting of adverse events with medicines used under the scheme.

Healthcare professionals should also consult the relevant detailed information provided by the company.

EAMS Indication

Tepotinib for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harbouring mesenchymal-epithelial transition (MET) exon 14 (METex14) skipping alterations

Information on the Pharmacovigilance system

Merck has appointed Clinigen to act on its behalf to manage the administration of the tepotinib EAMS programme via its dedicated access portal, Cliniport.

A physician experienced in the use of anti-cancer therapies registers and requests entry of their patient(s) onto the Early Access to Medicines Scheme (EAMS11648/0004) via Cliniport by completing a Patient Access Form.

Upon successful registration on the EAMS, each treating physician will be provided with an electronic version of the Physician’s Information Pack containing the following documents:

• EA MS Informed Consent Form
• Healthcare Professionals’ training slide deck on adverse event reporting
• EAMS Treatment Protocol – Information on the pharmacovigilance system and requirements for reporting safety data (this document)
• EAMS Adverse Event Reporting Form
• Patient Access Form to register patients, make first drug orders and subsequent re-supply requests
• EAMS Treatment Protocol
• EAMS Treatment Protocol – Information for Healthcare Professionals
• EAMS Treatment Protocol – Information for Patients
• EAMS Treatment Discontinuation Form

Adverse event/Adverse drug reaction (AE/ADR) reporting

All Healthcare Professionals (HCPs) involved in the care of patients on the EAMS will be instructed to report all adverse events (serious and non-serious), any exposure during pregnancy (including exposure from male participants of the EAMS) and lactation, medication errors, and overdose, within 24 hours to Clinigen, as specified in the relevant documentation within the Physician’s Information Pack which shall contain a relevant EAMS AE reporting form. HCPs will be required to confirm to Clinigen that they understand their obligation to report adverse events before EAMS registration.

Patients/caregivers will be trained by the EAMS physicians to recognise and document adverse events. Training will be provided by the EAMS physician at the time the patient enters the EAMS program.

Each patient will be allocated a unique identifier upon registration into the EAMS program for NSCLC harbouring METex14 skipping mutations. This will allow tracking of patients from baseline and throughout the treatment period.

Patients/caregivers will be instructed to contact their EAMS physician immediately if they experience any adverse events which shall be reported electronically via the EAMS AE reporting form directly to Clinigen or via the MHRA yellow card scheme. The EAMS AE reporting form will be available to HCPs via Cliniport for relevant entry and onward reporting. The EAMS AE reporting form can also be obtained from the Clinigen customer services team by contacting them via email medicineaccess@clinigengroup.com or telephone: +44 (0) 1932 824100.

Clinigen and Merck shall collate, store and process AE/ADR data as per internal processes and procedures which shall ensure quality assurance of these data. In the instances where AE/ADR information is either incomplete or missing, the Clinigen drug safety team will execute relevant follow-up activities to enable comprehensive AE/ADR assessment and evaluation. Collated data shall be stored in the global PV database and AE/ADR reports will be linked to the patient via a unique patient identifier. The EAMS AE form (which includes the EAMS number) is populated with a full description of the AE/ADR and submitted to Clinigen via Cliniport or by email to drugsafety@clinigengroup.com.

Merck UK is required to send AEs and ADRs suspected to be related to the EAMS products to the MHRA within the agreed timelines.

Training for healthcare professionals

All healthcare professionals involved with the management of the EAMS will receive a Physician’s Information Pack upon set up which includes training material for AE reporting. The material includes provisions for recognising, managing, and reporting AE/ADRs. HCPs must confirm they have read and understood their AE reporting obligations prior to EAMS registration. Alternatively, healthcare professionals involved with the management of the EAMS may request adverse event training from the Merck medical team by emailing EAMS-NSCLC@merckgroup.com.

To reaffirm the importance of reporting obligations, reminders shall also be provided throughout the duration of the EAMS program at the time of each order.

HCPs will inform patients/caregivers to report adverse events so they can receive appropriate medical attention.

Additional information

Registration onto the EAMS

The treating physician or appropriate members of their team will be required to complete a Patient Access Form (PAF) on Cliniport, providing information including but not limited to the patient baseline characteristics and details of patient eligibility. An overview of the registration information that will be requested, is listed below:

• Confirmation that the patient has given written informed consent and meets all the eligibility criteria
• Confirmation that the patient has advanced NSCLC harbouring METex14 skipping alterations confirmed by a test method using nucleic acids isolated from plasma or tumour specimens, and provision of the mutation report
• Demographics (initials, date of birth and gender)
• ECOG performance status
• Presence of brain metastases, if available
• Description of prior chemotherapy/immunotherapy/TKI therapy, if applicable, including response and reason for stopping treatment
• Description of prior chest radiotherapy, if applicable, including details of any radiotherapy-related toxicities
• Contraception/pregnancy check (female patients of childbearing potential and male patients with female partners of childbearing potential)
• Confirmation of baseline laboratory assessments in normal range, including bone marrow function, liver function and renal function tests
• Smoking history
• History of interstitial lung disease (ILD)

All HCP registration, patient registration and stock ordering will be done through Cliniport.

Periodic reports A 3-monthly periodic report will be submitted to the MHRA throughout the relevant duration of the EAMS

Contact details

All enquiries including registration, ordering, product complaints, medical information enquiries and adverse event reporting should be directed to Clinigen via Cliniport or the Clinigen customer services team via email medicineaccess@clinigengroup.com or telephone: +44 (0) 1932 824100.