Summary: Nazim Kanji, Senior Director of Corporate Development at Quotient Sciences, explores how strong partnerships between sponsors and CRDMOs streamline orphan, rare, and pediatric drug development. He highlights the unique challenges of these programs—such as limited patient populations, complex formulations, and regulatory hurdles—and explains how integrated services and early collaboration can reduce timelines and costs. 

Despite incentives in both the US and EU for developing orphan drugs for rare diseases, many conditions do not have approved or suitable treatments available. 

Many rare diseases impact children and can be fatal in infants and early childhood, making the need for new treatments even more critical. This article discusses how strong partnerships between drug developers and integrated contract research, development, and manufacturing organizations (CRDMOs) are vital for advancing treatments for rare and pediatric diseases.

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 can be crucial to ease the burden of drug development for these therapies and increase the likelihood of 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 (CRDMO) 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, as well as lend expertise in complex drug programs. These can include different drug formulations such as 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 on 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 that 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. 
 

References

1. The Orphan Drug Act: Implementation and Impact (OEI-09-00-00380; 5/01) (hhs.gov)
2. Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products (legislation.gov.uk)
3. FDA Approves Many New Drugs in 2023 that Will Benefit Patients and Consumers
4. Mirum scores 2nd FDA nod for rare liver disease drug Livmarli, this one to treat PFIC 

Pictured left to right: Dr. Andrew Lewis, Kieron Hall, Eric Bironneau

NOTTINGHAM, UK; 18 March 2024 – Drug development and manufacturing accelerator Quotient Sciences has announced major changes to its commercial and scientific executive leadership team, strengthening its position as a global leader in the sector.

New appointments include Dr. Andrew Lewis as Chief Scientific Officer, Kieron Hall as Chief Marketing Officer, and Eric Bironneau as Chief Business Officer who will each play a critical role in Quotient Sciences growth and strategic direction.
In his new role as Chief Scientific Officer, Dr. Andrew Lewis has responsibility for the company’s scientific and technological innovation. Andrew will lead the team of Drug Development Consultants and Scientific Research Fellows to grow Quotient Sciences’ global scientific expertise and recognition.

During his eight years with Quotient Sciences, Andrew has held various scientific leadership positions, most recently as Senior Vice President, Pharmaceutical Development. Prior to joining Quotient Sciences, Andrew was Director of Novel Drug Delivery Technologies at Ipsen.

Kieron Hall’s appointment as Chief Marketing Officer will see him lead the company’s strategic and growth initiatives and marketing organization. Kieron has been with the company in various global commercial leadership positions for more than 16 years, including Chief Commercial Officer. He was Head of Business Development in Europe for Cyprotex (an Evotec company) before joining Quotient Sciences.

Eric Bironneau has joined the company as Chief Business Officer, with responsibility for Quotient Sciences’ commercial organization across drug substance, drug product, and Translational Pharmaceutics® commercial lines, as well as for Quotient Sciences’ strategic partnerships. Eric      brings over two decades of commercial leadership experience to the company, including serving as Vice President, Global Sales & Business Development at Axplora and Novasep.

These latest changes come off the back of Thierry Van Nieuwenhove joining the company as CEO last October succeeding their long-standing leader Mark Egerton, who retired after 18 years with the company.

“We are committed to continuing our strategy of accelerating drug development, bringing new medicines to patients faster by breaking down traditional industry silos and leading with a science-first mindset for how we deliver customer programs,” said Thierry Van Nieuwenhove, CEO of Quotient Sciences. “I am excited to work with Andrew, Kieron, and Eric in their new roles, along with the rest of our leadership team, to continue to grow Quotient Sciences as a global leader in drug development.”

Quotient Sciences, a leading global pharmaceutical drug development and manufacturing accelerator, is proud to announce the successful completion of a US Food and Drug Administration (FDA) inspection of its bioanalytical facility in Alnwick, UK.

The regulatory inspection was conducted to audit three bioequivalence studies for three different insulin analogues for a renowned pharmaceutical company.

Quotient Sciences' Alnwick facility has specialty bioanalytical expertise and facilities for conducting bioequivalence studies, which play a crucial role in evaluating the similarity between pharmacokinetic properties of two proprietary preparations of a formulation. This is an essential step in the drug development process, enabling pharmaceutical companies to demonstrate that their generic versions of a drug are therapeutically equivalent to the corresponding branded product.

The US FDA inspection of Quotient Sciences' Alnwick facility is a significant achievement for the organization, highlighting its commitment to upholding the highest standards of quality and regulatory compliance. It reinforces Quotient Sciences' reputation as a trusted partner in the development of pharmaceutical drug products.

During the inspection, the US FDA thoroughly reviewed the facilities, systems, and processes at the Alnwick site. This comprehensive evaluation included assessing adherence to Good Laboratory Practice (GLP) and ensuring compliance with regulatory guidelines. The US FDA authorities inspected the facility for five days, from July 24 to 28, which concluded with a findings meeting that was also attended by the head of GLP for the MHRA Quotient Sciences' facility successfully passed the inspection with no observations or concerns noted, demonstrating its strong quality management systems and dedication to patient safety.

The Alnwick's site GMP facilities have previously been audited by the FDA and MHRA several times over the past 18 years, however this was the first US FDA audit that was specifically for bioanalytical work.    

MARK EGERTON, CEO of Quotient Sciences, "By successfully completing the US FDA inspection for these studies, Quotient Sciences has achieved another milestone in its mission to support the development of innovative medicines for patients worldwide.

"The results of the inspection further strengthen our track record for outstanding regulatory compliance at our Alnwick facility.

"At Quotient Sciences, we work diligently to maintain high quality standards and continuously improve quality platforms to ensure that we are meeting regulatory requirements that best support our global customers regulatory submissions"