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Pediatrics , Orphan Rare , Nazim Kanji

How strong sponsor and CRO/CDMO partnerships help streamline orphan/rare and pediatric drug development

Child with her mother and a healthcare provider in a clinical setting

In the US, rare diseases are defined as those affecting fewer than 200,000 people, and according to the EU definition, rare diseases affect fewer than five in 10,000 people [1, 2]. Many rare diseases are genetically inherited conditions and can include forms of full or partial blindness, hemophilia, and liver disease, as well as certain forms of cancer. Patients living with a rare disease often struggle with diagnosis of their condition, since a rare disease may come with broad symptoms that make it difficult to distinguish between diseases or between patients having the same disease. Some patients may even be misdiagnosed throughout their lifetime, and it may take years and multiple visits to health care providers (HCPs) and specialists to find suitable treatment options – if any do exist.

Since the passing of the Orphan Drug Act into law in the United States in 1983, the FDA has approved hundreds of drugs for rare diseases in the past four decades. Last year, the FDA approved 28 new therapies for orphan/rare indications, amounting to half of the new drugs approved [3]. Similar regulations also exist in the EU, but despite the incentives in both regions many rare diseases do not have approved or suitable treatments available. Constrained R&D budgets, challenging product development, and clinical recruitment, and reimbursement negotiations are among the obstacles faced by drug developers. Another reality of rare diseases is that many are prevalent in children, requiring additional time and cost to develop age-appropriate and palatable dosage forms.

Selecting the right development partner with a proven track record can be crucial in easing the burden and achieving market success in orphan/rare drug development. And because many rare diseases impact children and can be fatal in infants and early childhood, the need for new treatments is even more critical.

When selecting an optimal contract research, development, manufacturing, and service organization (CRO/CDMO) partner, the availability of integrated chemistry, manufacturing, and controls (CMC) and clinical research services from one company can be invaluable to streamline drug development processes. Additionally, the expertise of the CRO/CDMO can make all the difference in the development of age-appropriate liquid and solid dose formulations that are easier for infants and children to swallow. These can include solutions, suspensions, powder for reconstitution, and minitablets, and the taste and palatability challenges of these forms need to be overcome and confirmed by taste assessment studies.

Case study: Clinical assessment of Maralixibat for rare pediatric liver diseases via real-time personalized GMP manufacturing

Alagille Syndrome (ALGS), an autosomal genetic disease, and Progressive Familial Intrahepatic Cholestasis (PFIC), a group of cholestatic conditions, are both forms of rare pediatric liver diseases. Maralixibat is an oral small-molecule ileal bile acid transporter (IBAT) inhibitor that was first approved by the US FDA in 2021 for the treatment of cholestatic pruritus in patients with ALGS, ages 1 and older [6].

In its development, Quotient Sciences worked with the client on a high level of customization of the drug product to support an extensive Phase II/III clinical program based upon mg/kg dosing of patients. The client had the potential need to adapt the product during the treatment phase if there was a change in body weight of >10%.

A real-time adaptive platform was configured by Quotient Sciences which enabled a personalized solution product to be manufactured, labeled, and supplied globally, ready for dosing within 1-3 weeks of subject eligibility being confirmed. Products were re-supplied to each patient every 1-3 months based on individual needs and response to treatment. In total, six studies were supported involving manufacturing over 2,000 individual products for dosing in over 180 patients across 27 sites in 9 countries.

As of March 2024, Maralixibat is now also approved by the FDA for the treatment of cholestatic pruritus in patients ages 5 and older with progressive familial intrahepatic cholestasis (PFIC) [4], offering new treatment options for pediatric patients. 


  1. The Orphan Drug Act: Implementation and Impact (OEI-09-00-00380; 5/01) (
  2. Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products (