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Understanding Natural History Studies in Drug Development for Rare Diseases

Q &A with Michelle Berg, Vice President, Patient Advocacy, Abeona Therapeutics Inc.

20150610_Michelle Berg_0039[1]Developing a new drug for patients with a disease, particularly when it’s a disease that affects a relatively small number of patients,  poses unique challenges that do not apply to medical therapies for more prevalent diseases. However, an increasingly common, and particularly important method of addressing the special requirements for developing drugs for treating rare disease is by implementing a natural history study. This type of non-treatment observational study allows for better understanding of the natural progression patients with a rare disease experience and how this information can be assessed to facilitate the product development and regulatory review.

In a natural history study,  patients are assessed as they progress through multiple phases of disease manifestation. An important part of a natural history study is to better identify the tools and assessments needed to evaluate whether a potential drug is demonstrating efficacy and safety in the course of a clinical trial. The study enrolls affected individuals that have progressed through a pre-symptomatic phase and into different stages of disease manifestation. This is important because it helps clinicians evaluate different tools, such as MRI of specific organs, quality of life assessments, and neurological exams, as to whether patients may be able to have clinical efficacy measured after receiving drug treatment once enrolled in a treatment trial. This type of information is often not available, is incomplete, or anecdotal at best for many rare diseases.

Clinical stage gene therapy company, Abeona Therapeutics, is developing potential therapies for a number of rare diseases. Through their supporting foundations and clinical partners, they have completed multiple natural history studies in support of their Sanfilippo syndrome and Batten disease programs. Sanfilippo syndrome types A and B, also known as mucopolysaccharidosis (MPS) type IIIA and type IIIB are fatal, rare genetic diseases that affect children, and currently have no treatment or cure. Juvenile Batten disease, another rare and fatal genetic disease impacting children, is also without current therapy or available treatment.

We asked Abeona Therapeutics’ VP of Patient Advocacy, Michelle Berg, about the importance of natural history studies.

Q: What is a biotech company like Abeona looking for when embarking on a natural history study?

Berg: I’ll focus on the natural history studies involving children impacted by MPS IIIA and MPS IIIB. This was a special collaboration between our partnering hospital and three Sanfilippo foundations. All involved set out with the mutual goal of furthering the understanding for disease progression through this prospective study in both MPS IIIA and MPS IIIB (25 total participants) and to evaluate outcome measures and potential biomarkers. It was important to all to be well prepared for clinical studies and to be sure we were on the right path for safety and efficacy outcomes.

Q: What did the researchers in your natural history find?

Berg: They were able to determine which assessments provided meaningful information that would be relevant to design of the clinical studies. For instance, it became evident part way through that certain assessments were not helpful because of the inability for the participants to complete them and therefore they would not be clinically valuable. Without the type of study, it would not have been known and could have impacted the clinical trials.

Q: With the FDA now embracing and even funding natural history studies for rare diseases, why is this good news for patients?

Berg: With the most recent Guidance issued by the FDA on rare disease drug development, a big take away is that while the agency is not requiring a natural history study, it is strongly recommended prior to initiation of clinical trial. Earlier this year the agency further reinforced their recommendation by putting into place a grant through the Office of Orphan Products Development that could total up to two million dollars. Prospective studies may receive an award of up to $400,000 per year for up to five years while retrospective studies/surveys could be awarded up to $150,000 per year for up to two years. The FDA will start accepting grant applications in October of this year and hopes to initiate awards in Q1 of 2017.

Q: How has this natural history study helped Abeona now that its treated its first patient?

Berg: We’re pleased to have initiated enrollment in the Phase I/II gene transfer study for MPS IIIA. The information gained from the natural history study has helped to focus in on the important data to obtain and how to assess or measure. Additionally, Abeona is pleased to have also received allowance by the FDA for the proposed Phase I/II gene therapy study in MPS IIIB. The completion of the natural history studies enabled both of our MPS programs to move forward.

Q: What do parents need to understand about these studies?

Berg: It’s important to participate in these types of studies so scientists and clinicians can gain a solid understanding for the progression of the specific disease of focus. The information gained from behavioral assessments, MRI’s or biospecimen testing is helpful but so is the input from the parents and caregivers. Collectively, this data helps to shape the design of a clinical trial and what would be important outcomes to look for and the means to assess or test them.

Q: What are the next steps now for Abeona Therapeutics?

Berg: Abeona is focused on continued enrollment for the Phase I/II MPS IIIA trial and initiating the clinical trial for MPS IIIB. Our team of experienced professionals are also working hard to progress the gene therapy programs for juvenile Batten disease and Fanconi Anemia into clinical research.


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