The Rewards and Pitfalls of Orphan Drug Development: PhaseBio, Medidata’s 1,000th Customer, Rises to the Challenge

PhaseBio—a clinical-stage biopharma company developing improved biotherapeutics for orphan diseases, with an initial focus on cardiopulmonary disorders—has the distinction of being the 1,000th customer of Medidata Solutions. It was a beautifully sunny and breezy spring day when I drove west from New York City to the cozy suburban town of Malvern, PA to visit their headquarters and get more of an insight into their world.

“We really think we can deliver novel therapeutics to a population that has a really high need for novel therapeutics because their disease is relatively rare,” PhaseBio Chief Medical Officer John Lee, MD, PhD told me.

“Recruitment is always a challenge; to recruit right now about 60 patients or so in a study, we are thinking in terms of 30 to 40 sites, so only about one or two patients per site. That’s what you need to do sometimes in orphan diseases.” He was getting to the heart of the matter, the dilemma at the core of this niche therapeutic area: while developing orphan drugs is noble and ultimately worthwhile, it can also be costly, inefficient and daunting if not managed properly.

An orphan disease affects fewer than 200,000 people, according to U.S. criteria, and the Orphan Drug Act (ODA) grants special review status to a drug or biological product indicated for orphan diseases.

Currently in PhaseBio’s cardiopulmonary development pipeline are three treatments in pre-clinical, Phase I, and Phase II—indicated for cystic fibrosis, DMD-related cardiomyopathy, and pulmonary arterial hypertension, respectively. “A lot of times, the [clinical] protocol will change even at very late stages of development of that study,” Dr. Lee explained. “We as a small company in orphan diseases need a very streamlined, extremely efficient, and rapid development program. The ability to merge data or combine datasets or create datasets from the total amount of data from multiple studies is key for us.”

One of the latest innovations from PhaseBio is their proprietary biopolymer technology, which uses recombinant ELP biopolymers to control the half-life, bioavailability and physical characteristics of molecules for ease of administration and flexible dosing regimens. This enables the production of highly potent biopharmaceuticals with improved pharmacokinetics, slow absorption through a reversible phase transition and a prolonged circulatory half-life, and the use of a simple formulation (providing opportunities for co-formulation). It can even be manufactured efficiently.

Tenacity, adaptability, and resiliency have come to define the culture behind orphan development, and PhaseBio itself. “[We need partners in this space] to adjust quickly as we adjust quickly,” Dr. Lee said. Ironically, although designated “orphan,” PhaseBio seems on the fast track to becoming a conspicuous giant in its industry, yet everything about the company -- from its headquarters to its executives to its development pipeline—remains unassuming, humble and committed to this underserved and often forgotten patient population.

Dr. Lee ended our chat by telling me, “We’re really happy to be your 1,000th customer, and we’re really happy to have you as a partner, and we’re happy to celebrate together.” 

For Medidata, the feeling is absolutely mutual.