Monitoring post-approval drug safety has become a matter of increasing importance, as it enables us to maximize the safe use of registered medicines. Prior to registration, new ACTs are evaluated in clinical trials – like all new drugs – but trials are typically conducted in a limited number of patients (~2,000). Due to strict inclusion criteria in the selection of patients for clinical trials, these cohorts might not fully reflect the actual population receiving the treatment. To overcome this, it is necessary to collect post-approval safety data from larger cohorts of patients in real-life settings (pharmacovigilance).
1. How is pharmacovigilance usually carried out?
Post-launch safety data can be collected either passively or actively. In an ideal world all patients experiencing an adverse event would report it to their physician, who in turn would report it to the pharmaceutical company, who would report it to the regulatory authority. This is known as passive reporting. Unfortunately, most of the time this process does not work optimally, particularly in malaria-endemic countries; often patients and physicians simply don’t report these events.
Alternatively, pharmacovigilance data can be collected actively via Phase IV event monitoring studies. These studies are designed to detect adverse events classified as ‘rare’, which occur in between one in 3,000 and one in 5,000 patients. To detect such events, between 10,000 and 15,000 patients must be followed. They take the first course of treatment at the clinic and then go back home. A health-care worker visits the patient at home during the following week to see if there are any problems. In addition, a subset of around 10% of patients can be followed more closely if there are any specific concerns with the medicine.
2. Why is pharmacovigilance a priority for MMV now?
Our pipeline is maturing and we now have three co-developed ACTs that have been stringently approved. We must follow these new medicines to be sure their safety is equally as valid in the real world as it was in the clinical trials. We do not want to put patients at risk.
3. What are the key pharmacovigilance projects that MMV is working on?
Sanofi, DNDi * and MMV are undertaking a Phase IV field event cohort monitoring study to assess the real-life safety and effectiveness of the fixed dose ACT, artesunate-amodiaquine (AS-AQ), developed by DNDi, Sanofi and partners. The study has now recruited half the necessary patients in the health district of Agboville, Côte d’Ivoire, where AS-AQ is used as first-line treatment.
We are also planning a pharmacovigilance study of recently approved Eurartesim® (dihydroartemisinin-piperaquine, DHA-PQP)
with INESS** in four African countries: Ghana, Tanzania, Burkina Faso and Mozambique. The studies will begin once registration has been obtained in each of the countries. There are also plans to conduct a similar study with Pyramax® (pyronaridine-artesunate) in the Mekong Delta region, and in association with DNDi, with other ACTs in northern India.
4. Once completed, what implications might these studies have for the use of the medicines?
Sufficient evidence, be it positive or negative, can have the potential to change the recommendations stipulated on the drug label and therefore the way the medicine can be used.
* DNDi: Drugs for Neglected for Diseases initiative
** INESS: INDEPTH Effectiveness and Safety Studies of Anti-malarial Drugs in Africa