Rare-disease researchers face unique obstacles: Minoryx

By Jenni Spinner

- Last updated on GMT

(Olique/iStock via Getty Images Plus)
(Olique/iStock via Getty Images Plus)

Related tags Rare disease orphan disease Clinical trials Central nervous system Research Patient centricity

A representative of the rare-disease specialist firm outlines the unique obstacles of orphan CNS disease research, and how professionals can overcome them.

Pharmaceutical companies and their research partners well know that as challenging as drug development and trials can be, rare and orphan disease studies are even more daunting. Figure in the singular challenges faced in trials focused on central nervous system (CNS) disorders, and these obstacles become even more formidable.

Marc Martinell, CEO of rare and orphan disease solutions provider Minoryx, discussed the complications involved in rare CNS research, how the field is evolved, and ways to deal with the challenges. He also shared news of recent studies the company has contributed to.

OSP: Could you please share your thoughts on the differences between how rare disease research is handled, and funded, as opposed to other conditions?

MM: Even though there has been significant progress in the past decade in the rare disease space, there is still significant work that needs to be done. Investment in rare disease research has clearly increased, but it is still very far from reaching the scale of investment on more prevalent conditions. The key limitation in the rare disease space lies in the lack of understanding of basic science, rare disease pathology and progression.

In rare diseases, the efforts are mainly driven by academic research and/or research supported by patient advocacy groups, hence the amount of funding is substantially limited. Furthermore, the conduction of clinical trials in the rare disease universe remains a challenge as the patient population is significantly small and diverse in terms of thousands of different known, or even as-yet-unknown indications. As a result, there are still many unmet needs in the orphan disease space and many scientific and operational issues to be addressed.

OSP: Specifically, how are rare CNS disorders handled and funded?

MM: Conventionally, basic science is usually funded by academic research and patient advocacy groups. The wider industry normally gets involved once there are primary outcomes that can be the basis of a drug development program.

There is less investment on indications where this “seed” research is not available, as there are significant issues of cost-effectiveness. The rarity and low prevalence of those diseases adversely affect the interest of big pharma companies in terms of early-stage investments. This is why funding resources are relatively small and rare diseases are particularly incorporated in the pipelines of SMEs.

In order to overcome this obstacle, we need to establish transnational collaborations with a well-connected ecosystem of various stakeholders from academia, hospitals and patients, industry, and governments.

OSP: You mention that there are “no clear pathways” for approval of orphan drugs. Could you please elaborate, and share any suggested solutions you might have?

MM: The lack of clear pathways comes from the lack of understanding of the natural progression of the disease as well as the relevant endpoints. This is usually established after some initial developments make it up to the market, hence for the frontrunners is usually unknown territory.

OSP: What else could be done to make orphan drugs more appealing to regulators and reimbursement organizations?

MM: Orphan diseases affect more than 300 million people today, with the vast majority of incidents (85%-95%) being considered life-threatening. In addition, developing therapies for orphan diseases is challenging as the data available for each indication are limited and there are no benchmarks or route maps.

More complex and risky therapeutic developments need specifically favorable regulatory frameworks. This is because of the significant challenges of developing orphan drugs with rules and standards designed to apply in wider cases and circumstances.

Regulatory bodies have shown some flexibility to rare disease drug development, recognizing unique challenges that can hinder efficient and effective traditional clinical trials. There is still more work to do with regulatory frameworks, in order to highlight and reinforce the future of orphan drugs.

OSP: Why is it important for regulators/approvers to look at the wider results of orphan condition research?

MM: There is an emerging need for strategic regulatory decisions to drive the future of orphan diseases. A stable, less fragmented, agile and pragmatic regulatory framework is a prerequisite for the progress in the orphan disease field.

Enhancing the interest for R&D investments by securing and strengthening IP and incentives, shifting to an alternative clinical trial model based on new type of designs and real-world data and streamlining access requirements to reach more and more patients could be the first set of actions to facilitate the global collaborations in the orphan disease space and facilitate the work and involvement of regulatory authorities.


OSP: Could you please share an overview of the recent Minoryx studies in adrenomyeloneuropathy ​(AMN) and ​Friedreich’s Ataxia (FRDA)? What were some of the most notable results, and promising signs, you could share?

MM: In both studies, we confirmed that in patients we can safely achieve the target levels of PPAR gamma engagement in the CNS. This is also translated in both studies in clinical benefit for patients.

In AMN, being a much larger study, results became clearer showing that leriglitazone has an effect on key aspects of the disease such as myelopathy and cerebral lesion progression, the second being a life-threatening indication. In FRDA, the study was a proof of concept, hence much smaller, but showed strong signals on relevant biomarkers such as iron accumulation in the brain and functional improvement of upper limb ataxia.

OSP: Are there any changes regulators could make in their approaches and processes that could improve the outcome for researchers developing treatments for rare diseases?

MM: It is crucial that all regulatory authorities and involved parties identify the differences between orphan diseases and other conditions, so that it becomes widely understood that the development of new approaches and frameworks is mandatory to handle these diseases. Regulatory standards need to be updated to ensure that the patients suffering from orphan diseases receive safe and efficacious treatment options and this can be achieved only by establishing global open collaborations that will foster further research on the field.

At the moment the orphan drug legislation is under revision by the European Commission while it’s a critical time for further orphan products and pediatrics development on a global scale. 

OSP: Is there anything you’d like to add?

MM: Orphan diseases have a devastating impact on patient’s lives. It is crucial for us to remain focused in solving the current research and regulatory challenges in the space while staying committed to ensuring the availability of new treatments for patients with orphan diseases worldwide.

The COVID-19 pandemic has taught us that a collaborative approach model with comprehensive data sharing combined with globally harmonized and speedy scientific assessments can deliver valuable outcomes for the global population, a paradigm that can also be applied in the orphan disease universe and other cases of high speed.

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