For sponsors developing interventions for one of the 6,000 rare diseases identified, there are many tough challenges to face, ranging from recruitment from a small pool of potential participants to the need for innovation in trial design.
Working with an orphan disease CRO can strengthen a rare disease trial with the experience and expertise needed to tackle these challenges. Here we look at the therapeutic area, some of the biggest challenges, and Siron Clinical’s rare disease and orphan study expertise.
About Rare Diseases and Orphan Indications
According to the European Medicines Agency (EMA), about 30 million people in the EU are living with a rare disease. Medicines developed to treat these rare diseases are called ‘orphan’ medicines. In the US, the Orphan Drug Designation program defines orphan medicines as “those intended for the treatment, prevention or diagnosis of a rare disease or condition, which is one that affects less than 200,000 persons in the US or meets cost recovery provisions of the act.”
Since Siron Clinical was founded over 20 years ago, we have been involved in clinical studies with rare diseases. The rare disease therapeutic area is varied, and no two rare diseases are the same. This provides challenges: is it possible to have a standardized approach to trials? What special requirements do patients have?
Addressing Challenges as a Rare Disease CRO
There are some standardized aspects to the trial process, regardless of the study area. Some of the general project management aspects we need to consider here include: the timelines of regulatory submissions, which differ depending on the region; training of the study team; and the implementation of risk assessments.
Some of the challenges and special requirements a sponsor or orphan disease CRO needs to consider are related to the patient population and therefore directly linked to the orphan indication. Because each orphan indication is rare, the pool of potential clinical trial participants is small, making recruitment inherently challenging
It’s therefore necessary to identify patients ahead of time, before the recruitment phase, and work on patient engagement. This often involves working closely with patient groups, for example. It’s also important to plan how we will work together, including considering logistics. This is where decentralization and digital technologies become helpful, as they can reduce the need for patients to travel long distances to a study site.
An orphan disease CRO working with a sponsor on a rare disease clinical trial will also need to deal with the challenges that come with every clinical trial, such as ensuring we work within ethical guidelines and remain compliant with all the relevant regulations.
Pediatric Rare Disease Clinical Research
Almost three-quarters of the 6,000 or so rare diseases that have so far been identified are genetic, and 70% of them start in childhood. Rare diseases treatments are difficult to develop, trial and approve, and this is particularly the case for pediatric rare conditions.
There are many challenges in pediatric clinical trials that apply to rare disease clinical trials in this group. For example, parents or guardians need to give consent for minors, so investigators need to work with families and consider their needs in addition to those of the patients themselves. Again, when it comes to logistics, this is also a factor to take into account, as pediatric clinical trials can be burdensome for families.
A pediatric CRO can help address the additional set of considerations that come with pediatric rare disease clinical research. Pediatrics CRO services can be adjusted, particularly on a Functional Service Provider (FSP) basis, to the individual needs of the trial. And in addition to the pediatrics trials expertise a rare diseases CRO partner can bring, they may also come with a network that can help forge critical connections with patient groups, trial sites and other study groups.
Our Specialized Therapeutic Expertise: Orphan Indications
Specialized therapeutic expertise is one of the strengths Siron Clinical brings to clinical trials, including as an orphan disease CRO. We have worked on 120 clinical trials over almost 25 years, including pediatric, cardiovascular and orphan indication studies. Each therapeutic area brings its own challenges, and orphan indications cover a broad range of diseases and medications.
Our experiences of overcoming implementation challenges for rare disease clinical trials have equipped us to tackle disease trial challenges across a range of indications. We have learned that when we’re well prepared and take all considerations into account, we have control of the project and can manage it successfully.
As an orphan disease CRO, it is essential that we have expert CRAs available to promptly address any questions or provide support as needed. This can range from finding practical solutions for the sites to providing useful support for administrative questions.
Across all therapeutic areas, collaboration is the foundation of our success. We build strong collaborations with our clients, and this has resulted in many long-term partnerships spanning multiple international trials. Direct contact with sponsors is vital, particularly around patient eligibility questions. For US sponsors, this means that having an EU point of contact to address eligibility questions can be very helpful.
Our specific experience includes:
- Pulmonary Hypertension
- Chronic Thromboembolic Pulmonary Hypertension
- Enzyme replacement therapy
- Primary Biliary Cirrhosis
- Primary Sclerosing Cholangitis
- Familial Adenomatous Polyposis
- Alpha-1 Antitrypsin Deficiency
- Peanut allergy
Trialing the World’s First Oral Therapy for Peanut Allergy
One example of a successful orphan indication study that Siron Clinical worked on as an orphan disease CRO was the PALFORZIA trial. PALFORZIA is an oral treatment for peanut allergy, which affects an estimated 1 in 50 children.
The treatment was developed by Aimmune Therapeutics, which, when our collaboration started, was a young, dynamic, growing organization. We took the opportunity to support them by getting studies and study centers up and running to find a treatment for this deadly allergy.
We collaborated with Aimmune Therapeutics on phase III clinical trials of PALFORZIA, which was then called AR101. They were complex trials, involving different geographic regions, entry criteria, dosing periods and primary efficacy endpoints. There were three projects:
- A phase III study in children and adults, called PALISADE (we provided regulatory support and clinical monitoring services)
- A phase III study in children, called ARTEMIS (we supported the regulatory submission process and were responsible for the clinical monitoring)
- An open-label long-term safety study, which is ongoing (we are responsible for clinical monitoring)
Requirements were stringent and the goal was FDA approval. The studies were successful, and the FDA approved PALFORZIA as the first and only oral immunotherapy for peanut allergy in patients aged 4 to 17 years old.
Orphan disease CRO support can help sponsors succeed in their rare disease clinical trials. Contact Siron Clinical to find out how your trial could benefit from our rare disease CRO services.
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