EU Post Marketing Requirements for Cell and Gene Therapy Studies

Post-marketing requirements within the European submission process offer conditional approval more flexible than FDA. Rachel Smith, Portfolio Director for Veristat, discusses the three types of post-marketing requirements that can be requested by the EMA and draws upon the recently approved therapies – Tecartus, Zolgensma and Libmeldy, Skysona and Abecma– for real-world context. 

Transcript

Speaker 1: 0:00

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Speaker 2: 0:15

Welcome to our podcasts, advancing revolutionary therapies, a podcast presented by the center for excellence for cell and gene therapies by barista. My name is Rachel Smith. I'm a portfolio director here at Veristat and I work with our clients in cell and gene therapies, providing operational excellence from strategic consulting to clinical trials. And post-marketing commitments today. I'll be discussing post-marketing requirements now for 17 therapies. It's rarely the case that sponsors will have a comprehensive data set at the time of bla submission in the us or MAA submission in the year. This is particularly true for therapies in rare disease where patient populations are particularly small. And for therapies where we have that 15 year followup requirement, I'm pleased to say that for these reasons, regulators really have taken a prognostic approach for approvals of these therapies, but almost always require some form of post-marketing study. So the objective of today's podcast is to define the types of post-marketing requirements and how these can be implemented in practice. And I'm going to focus on the European process because they do offer conditional approval, which is much more flexible than the accelerated approval process available through FDA. Under the EMA process, most synergy therapies will be submitted for conditioning marketing approval as they will fall under the criteria of medicinal products without comprehensive data intended for the treatment prevention or medical diagnosis of seriously debilitating or life-threatening diseases. And they will fulfill an unmet medical need. They will have a favorable risk benefit balance. And the benefits of immediate availability of the product will outweigh the risks related to the additional data still being required. And on top of that, the expectation is that the sponsor or applicant will likely be able to provide a full comprehensive dataset. At some point, conditional marketing approvals. The post-marketing commitments are agreed with the agency as part of the risk management plan, which forms part of the MAA submission. And that approval is reviewed annually. Conditionally approved products are anticipated to be converted to a full standard approval. Once post-marketing commitments are met and there are three types of post-marketing requirements that can be requested by the EMA. So the first is a post authorization safety Sully or pass. The second is a post authorization efficacy study or pace, and the third and final post authorization measures. Pam we'll start with pass. So pass is defined as any study related to an authorized medicinal product conducted with the aim of identifying characterizing or quantifying a safety hazard, confirming the safety profile of the medicinal product or measuring the effectiveness of risk management measures. So you can see why these are often requested for Saturday therapies. Past studies can be interventional, but more often than not, they are non-interventional essentially, we can look at these as prospective registry studies for patients treated with commercial products. The intention is to observe these patients in a standard of care setting and monitor any potential safety signals post-treatment for either five or up to 15 years, depending on your product type, thinking about therapies approved in 2020. So we have to[inaudible] and those approved to date in 2021 are in a backpack. Every single product has required some form of past study demonstrate long-term safety, and also as a tool for continued assessment of efficacy, particularly in those, in the rare disease arena, but patient populations with the pace study is similar to pass in that it tends to be a prospective registry study for patients treated commercially. But the key difference is that these studies are only requested if there are any concerns on any aspect of product efficacy, which can only be resolved post-market for example, imagine diseases accessing a wider population with potentially greater co-morbidities or more severe disease, or where the understanding of the disease or the clinical methodology or the use of the product and to real life conditions could impact on that initial efficacy evaluation that was established as part of your clinical development plan. It will key example of the past years is so guns. So guns at the point of marketing authorization required several pace studies, um, to demonstrate efficacy in the patient population. So in spinal muscular atrophy or SMA, now this was specifically for SMA patients younger than six months, and in pre-symptomatic SMA patients younger than six weeks, um, both with specific genetic subtypes, the disease, these patients studies were actually requested as the clinical trial data had been limited in these groups. It is a rare disease with SMA. And obviously we are talking about these genetic subtypes of the condition as well. Now we've so gun's not the reason it was approved is that I have the potential to offer exceptional benefit. We're talking about a therapy that potentially allows for babies who might not otherwise reach their second birthday to potentially be cured of that condition. So you can see here, the, the risk benefit here and why is organismic was approved these conditions now pass a paced studies can fall under a third category of post authorization measures or poems, but patterns may also encompass other conditions like provision of the 15 year long-term follow-up data as was the case of sky center or provision of data from ongoing studies as requested for a backnet or even tackle things like manufacturing or assay validation, for example, would love lip melty. Once conditions was to reduce the product testing release timelines with patients. One other example of a pound that Springs to mind is with an older product that at the time of approval, there were new validated assays for insertion Sinai assess the type of factor used in gene therapy. So as part of the risk management plan at the time, it was agreed with the agency. That method would be developed, validated, and then used to retrospectively test samples from clinical trial patients are patients treated commercially. So only by working collaboratively with the agency, was it possible to actually allow a therapy that had offered true benefit to the patients to get to those patients who needed it most? Now, this was a really important case because working in cell and gene therapies as several more, now we are at the cutting edge of medicine. And quite often we will be facing similar obstacles where the science might not quite be there yet, but we're moving to market because we do have something that could truly benefit the patient population that we're working in. So the podcast today is intended to be a high-level overview of post-market requirements in Europe. The take home message is to assume post-market data will be required and include a plan for the prospective registry study, um, provision of ongoing study or long-term followup data in both your clinical development plan and marketing package. But most of all work with the regulators, we're all working to a common goal and to improve the lives of patients by ensuring safe and effective therapies access. And by keeping the conversation going throughout your clinical recess, you can ensure that you're on the same page as the regulators guarantee success when it comes to marketing. And post-marketing first that managed the clinical trials for the first teen therapy to be approved in the Western world. And as trailblazers, we continue to be actively involved and kindness. This field, we encourage you to listen to future episodes of the podcast. As we delve deeper into some of these issues and other important topics in some detail therapy, I hope this has been valuable to you. Please reach out to our expertise for the links available on the first.website. Should you have any questions and we'll be back talking to

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