Making rare disease successes more common

Gareth Macdonald

June 3, 2019

2 Min Read
Making rare disease successes more common

Complex pathologies and small patient populations make rare disease R&D difficult according to Alexion, which says recent FDA guidelines are welcome.

At large biopharma firms, rare disease drug R&D projects are becoming common. Their high revenue potential combined with IP advantages afforded to such products makes them an attractive focus for developers.

For example, orphan drug designation entitles firms to reduced fees, tax breaks for trials and extended market exclusivity. Investors also welcome such designation. According to one study, developers granted orphan status see, on average, a 3.36% increase in stock price.


But despite being a rare opportunity, rare diseases are also an R&D challenge says Alexion Pharmaceuticals spokeswoman Megan Goulart.

“In rare diseases, a poor understanding of disease mechanism and progression, as well as small and heterogeneous patient populations create unique challenges for the design and conduct of clinical studies to develop therapies for patients.”

She added that, “Natural history studies are important to understand rare diseases and help design robust development plans. Especially when small patient numbers make it difficult to enroll a comparison arm in a standard clinical study approach, a natural history cohort could serve as a control.”

Natural history

The importance of understanding rare disease natural history was stressed by the US Food and Drug Administration (FDA) in draft guidance released in February. Among other things, the agency advised developers to “evaluate early the depth and quality of existing natural history knowledge to determine if it is sufficient to inform their drug development programs.”

Goulart told us “Alexion welcomes the FDA guidance on natural history studies as part of the agency’s commitment to advancing the development of therapies for patients with rare diseases. The FDA’s evaluation and advice have been very useful for companies facing challenges in this endeavor.

She added, “We also welcome the consolidation of current experience in this guidance document and are contributing to the Pharmaceutical Research and Manufacturers of America’s (PhRMA) response to the FDA.”

Finding patients

Clinical development is another challenge for rare disease focused companies. For common conditions, finding people willing to take part in trials is fairly straightforward.

For rare diseases, finding patients is much harder according to Goulart, who told us, “In rare and ultra-rare diseases, patient populations are much smaller than in more common diseases, physicians are much less familiar with the disease, the diagnosis is much more challenging, and the heterogeneity among patients much higher variability in the age of onset and progression of diseases for example.”

Such challenges mean modified protocols are necessary she continued, explaining that rare diseases usually necessitate more geographically dispersed trials.

“It is not uncommon to have only one patient per study site. In addition, the number of clinical centers with both the expertise in the investigated rare or ultra-disease and the expertise required for conducting clinical studies is much more limited,” Goulart said.

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