The regulator’s perspective: How should new therapies and follow-on products for MS be clinically evaluated in the future?

Abstract

Abstract:Background: Although there is still no cure for multiple sclerosis (MS), the introduction of several innovative drugs with modes of action different from that of the existing drug arsenal and the progress in monitoring disease progression by imaging and using biomarkers are currently causing a knowledge surge. This provides opportunities for improving patient disease management. New therapies are also under development and pose challenges to the regulatory bodies regarding the optimal design of clinical trials with more patient-focused clinical endpoints. Moreover, with the upcoming patent expiry of some of the key first-line MS treatments in Europe, regulatory bodies will also face the challenge of recommending marketing authorisation for generic and abridged versions based on appropriate requirements for demonstrating equality/similarity to the innovator's product. Objective: The goal of this article is to improve the understanding of the relevant guidance documents of the European Medicines Agency (EMA) on clinical investigation of medicinal products and to highlight the issues that the agency will need to clarify regarding follow-on products of first-line MS treatments. Conclusion: Today, it is clear that close collaboration between patients, healthcare professionals, regulatory bodies and industry is crucial for developing new safe and effective drugs, which satisfy the needs of MS patients.

Conclusions: Calls to action for improving the life of MS patients and their families

“…Call 3: perform patient research to (re)define treatment goals/endpoints from a humanistic/ patient perspective point of view In the current marketing authorisation, HTA and reimbursement decisions emphasis is still placed on shortterm endpoints, that is, the reduction of the duration, severity and sequelae of relapses. 8 Nevertheless, they recognise that the main benefit of DMDs or treatment lies in their ability to delay the progression to an EDSS of 6 (when walking aids are required to remain mobile). Moreover, there is research suggesting that patients prefer to delay disability progression and prevent serious adverse events over decreasing relapse rate.…”

“…8 Therefore, they encourage researchers and clinicians to develop and validate new tools for capturing disability in a broader sense than just mobility/walking ability. 8 In addition, researchers and clinicians should develop and validate with priority instruments that better capture patients' expectations from MS treatment and which can be self-administered and completed by the patient. 8 This includes bothersome, albeit often hidden, MS symptoms for society such as fatigue and cognitive decline, due to which patients may often refrain from education and/or work.…”

“…8 In addition, researchers and clinicians should develop and validate with priority instruments that better capture patients' expectations from MS treatment and which can be self-administered and completed by the patient. 8 This includes bothersome, albeit often hidden, MS symptoms for society such as fatigue and cognitive decline, due to which patients may often refrain from education and/or work. 8 The EU should be aware of the importance of funding research focused at developing these new tools.…”

“…8 This includes bothersome, albeit often hidden, MS symptoms for society such as fatigue and cognitive decline, due to which patients may often refrain from education and/or work. 8 The EU should be aware of the importance of funding research focused at developing these new tools.…”

“…8 Attempts of the regulators such as the 'adaptive licensing approach', which gives faster but conditional initial marketing authorisation and accelerate quick access to new treatment, are also highly encouraged. 8 Call 8: develop separate EMA guidelines for evaluating follow-on products of non-biological complex drugs The upcoming expiry of patents of first-line DMDs such as INF and GA holds the potential that cheaper follow-on products will increase access to treatment for MS patients living across Europe. However, patients and HCPs should be reassured by the regulators and governments/Ministries of Health that the guidelines required to demonstrate 'similarity' will ensure that the developed follow-on products are indeed as effective and safe (in the long term) as their originator products.…”