In short
- Trials for biosimilars in MS are incredibly important to ensure the treatments reach a wider range of patients for a longer time, and can have positive impacts on local communities
- A biopharmaceutical sponsor approached PSI for guidance with their global trial of a biosimilar for MS
- The sponsor highly valued PSI’s experience in MS and with biosimilars
- Challenges occurred along the way:
- Unavoidable vendor delays with IP put the trial on hold for significant time, yet PSI’s maintenance of relationships with pre-activated sites meant fast study resumption when the problem was solved
- Difficulties with one country’s MOH meant the trial was rejected there; however, quick reactivation of backup sites meant no perceivable delay occurred
- The trial was expected to have high screen failure rate; PSI carefully managed this along with appropriate recruitment activities, maintaining the projected screen failure rate
- The trial met its milestones on time, supporting successful regulatory approvals in major markets
The challenge
A biopharmaceutical sponsor contacted PSI based on positive word of mouth. The sponsor’s challenge was simple, and yet operationally complex: They needed to have their product, a biosimilar for MS, approved as soon as possible.
The sponsor was confident that choosing PSI would provide the best outcome, based on PSI’s prior experience with MS and with biosimilars in different therapeutic areas.
MS, biologics, and biosimilars
Almost 2 million people worldwide live with multiple sclerosis (MS [1]). Despite intensive investment in searching for curative treatments, current therapies are disease-modifying, generally to reduce disease progression and manage symptoms [2]. New therapies, such as biologics, are highly effective (especially when used early) in preventing relapses and stopping the formation of new lesions in the brain.
These biologic therapies are associated with high expense, making their use prohibitive in certain regions with limited resources. Biosimilars fulfil multiple roles – in addition to being cheaper than originator biologics (benefiting patients and the healthcare systems), they can potentially be manufactured locally (stimulating the economy), and their use after patent expiry is beneficial to patients who require treatment continuity.
Accordingly, clinical trials for biosimilars have a different approach from those of the traditional drug development phases. As the aim is to prove comparability, equivalence, or non-inferiority to an existing biologic, certain steps can be logically abbreviated or skipped. This generally means phase 1 data can be limited and dose-ranging studies are not required [3].
This does not mean that the journey to biosimilar approval is necessarily smoother than for a new biologic – the absence of the ‘traditional’ steps in drug discovery can make some regions and countries hesitant to participate in biosimilar trials, and strong, continued regulatory oversight and PV is required to ensure comparable efficacy and safety [4]. From an operational perspective, finding the countries where there will be sufficient interest in the biosimilar from site and patients (i.e., where the original isn’t available or isn’t covered by insurance) is crucial.
The story
A perfect beginning
Initial discussions helped to set the scene – collaborative, experience-sharing open talks on topics such as legislative and regulatory experience, and operational pitfalls, helped build confidence that PSI was able to deliver the trial on time. During the trial setup phase, the sponsor handed operations to their partner to allow the old sponsor to continue with pipeline development. PSI was on hand to help with the transition, running handover meetings and investigator meetings, and liaising with the heads of both biopharma companies to ensure efficient transition of the relationship and knowledge.
Obstacles along the way
As expected, challenges arose as the trial progressed.
There was an immediate problem with IP production. Neither the sponsor nor PSI could do anything about this. Even though a large number of SSVs had been completed by this point, the sponsor had to put the study on hold while the problem with the vendor was fixed. Both sponsor and PSI anticipated the study to restart and focused on keeping sites engaged, and preparing for the go-ahead. Continued evaluations (both over the phone and in-person) in the pre-activated sites meant the trial could be quickly restarted a few months later when the IP finally came through
While often expedient and understandable to begin biosimilar trial submission while still generating data (e.g., phase 1, or PK/PV), incomplete submissions can cause difficulties with individual regulatory authorities. Discussions with the MOH of one country were particularly difficult – the protocol was initially rejected by the ethics committee, which requested additional safety monitoring requirements aligned with those of the reference biologic. After a full resubmission, where the safety profile of the biosimilar was recommended to be the same as the biologic (alongside additional information and data), the country’s MOH unfortunately chose to reject the study. A significant number of potential sites were immediately lost. Losing this many sites could have created significant burden, but by identifying backup sites early on and staying in contact with them throughout this process, the team activated them quickly and no time was lost due to this setback. In today’s landscape, it is generally advised to have phase 1 data available as soon as possible to reduce any potential delays
The biosimilar (and originator biologic) can pose a remote but serious adverse event (AE) risk in immunocompromised patients. To minimize the chance of this AE occurring, the enrollment criteria were very stringent, selecting for patients with a low chance of developing this AE. This meant the projected screen failure rate would be high. Investigators received specific education and training on the AEs to ensure that they were making the correct decision for their patients. Enrollment was achieved on time through careful management of screen failure overshoot, and ongoing patient recruitment activities
A perfect ending
Despite these challenges, the trial comfortably met its milestones on time. The sponsor and PSI were ecstatic at how the trial went and held a co-celebration, a testament to the closeness of the relationship developed through the hardships. Most importantly, the data produced supported the successful regulatory approval of the sponsor’s biosimilar in major global markets.
Thank you very much for your dedicated and highly committed leadership for the […] trial. Certainly a great success […]. We look forward to continuing the good collaboration with you and your team.
Key takeaways
Choosing a CRO to partner with can seem at times like a leap of faith – except, it isn’t. Critically evaluating their experience and expertise is key to making the right partner choice and to successfully navigating milestones and unexpected challenges together. After a few years of drought, clinical trials in MS are making a comeback. Choosing a CRO with experience in the field and the desire and drive to perform is now even more crucial.
Your MS trial deserves a specialized global team
Abbreviations
AE, adverse event;
CRO, contract research organization;
MS, multiple sclerosis;
PK, pharmacokinetics;
PV, pharmacovigilance;
SSV, site selection visit.
References
1. Khan, G. and M.J. Hashim, Epidemiology of Multiple Sclerosis: Global, Regional, National and Sub-National-Level Estimates and Future Projections. Journal of Epidemiology and Global Health, 2025. 15(1): p. 21.
2. Sabatino Jr., J.J., B.A.C. Cree, and S.L. Hauser, New Horizons for Multiple Sclerosis Therapy: 2025 and Beyond. Annals of Neurology, 2025. 98(2): p. 317–328.
3. Isaacs, J., et al., The biosimilar approval process: how different is it? Considerations in Medicine, 2017. 1(1): p. 3–6.
4. Knox, R.P., V. Desai, and A. Sarpatwari, Biosimilar approval pathways: comparing the roles of five medicines regulators. J Law Biosci, 2024. 11(2): p. lsae020.
