Biotech Innovation Boosts Orphan Drug Development - Economic incentives and regulatory flexibility can spur development of treatments for small patient populations. - BioPharm International


Biotech Innovation Boosts Orphan Drug Development
Economic incentives and regulatory flexibility can spur development of treatments for small patient populations.

BioPharm International
Volume 21, Issue 7

In both the US and EU, separate offices review the resulting market application for an OD. At the FDA, there are differences among new drug review divisions in how much leeway they grant manufacturers in modifying clinical testing to reflect small populations available for clinical trials. OOPD doesn't "meddle" in safety and efficacy assessments, says OOPD director Timothy Cote, but his office often provides input requested by review divisions.


In addition to research and regulatory issues, formulation and production difficulties can stymie OD development. Many orphan treatments involve complex biotech manufacturing systems that can be difficult to scale up or move to new facilities. The FDA recently blocked Genzyme's plans to shift production of its treatment for Pompe disease to a larger facility, a decision illustrating that even life-saving ODs are not exempt from quality standards. The agency's concern was that Myozyme (alglucosidase alfa) from Genzyme's 2000-L facility (in Allston, MA) exhibited differences in the carbohydrate structures of the molecule compared to batches from its 160-L plant (in Framingham, MA).

The FDA requested data from larger clinical trials to ensure that the differences do not affect product quality, and Genzyme filed a new biologics license application with additional clinical data. But the delay will cost Genzyme some $50 million in lost sales plus the cost of providing Myozyme for free to some patients pending scale-up to the larger plant. The silver lining for Genzyme and other biotech manufacturers is that the FDA's demand for additional clinical data to support a manufacturing change illustrates the hurdles that will face companies seeking market approval for follow-on biotech therapies in the future.

The Genzyme scale-up problem also points to the need to provide researchers and small companies with assistance in product formulation and clinical supply production. The National Institutes of Health's Rapid Access to Interventional Development project offers toxicology testing, scale-up production for clinical trial lots, and other services to support the development of novel treatments by academics and nonprofit organizations. Similarly, the Center for Orphan Drug Research at the University of Minnesota College of Pharmacy provides assistance in drug synthesis, formulation, pharmacometrics, and other processes to small companies that lack in-house expertise in these areas.


To spur more OD development, advocates want to expand the OD grants program, which has been stuck at a $14-million budget level for years and suffers from eroded buying power. Congress regularly authorizes additional funding, only to see the number cut by appropriators.

Another FDA project is to rescue abandoned orphans. The designation (1,850) and OD approval (326) numbers mean that some 1,500 drugs identified as ODs have never come to market. The FDA plans to cull through those abandoned applications to "find the diamonds hidden in all that gravel," Cote said.

OOPD also is implementing a new priority review voucher program established by the FDA Amendments Act to spur development of drugs to treat tropical diseases that are rare in the US. A company developing a treatment for malaria, for example, could sell the voucher to another company and use the proceeds to offset development costs. It's a complicated program, but could help spur innovative approaches for tackling neglected diseases worldwide.

Jill Wechsler is BioPharm International's Washington editor, 7715 Rocton Avenue, Chevy Chase, MD 20815, 301.656.4634,

blog comments powered by Disqus



Bristol-Myers Squibb and Five Prime Therapeutics Collaborate on Development of Immunomodulator
November 26, 2014
Merck Enters into Licensing Agreement with NewLink for Investigational Ebola Vaccine
November 25, 2014
FDA Extends Review of Novartis' Investigational Compound for Multiple Myeloma
November 25, 2014
AstraZeneca Expands Biologics Manufacturing in Maryland
November 25, 2014
GSK Leads Big Pharma in Making Its Medicines Accessible
November 24, 2014
Author Guidelines
Source: BioPharm International,
Click here