How the Orphan Drug Act Impacts Rheumatologic Disease Treatment

Under 30 years of the US orphan drug act, 14 orphan drug programs with anti-rheumatic or supportive compounds for 6 rare rheumatologic conditions were approved by the FDA between 1983 and 2013.

For a quantitative analysis published in the Orphanet Journal of Rare Diseases, researchers searched the FDA’s publically available database for orphan drug designations, which were then categorized according to drug class or pharmacologic category.

For the drug class, compounds were grouped as either small molecules or biologics, while the pharmacologic category grouped compounds based on their mechanism of action taken from the FDA label.

Standard methods of descriptive statistics with SAS Enterprise Guide version 5.1 was used to analyze the data. The results of the analysis showed that overall, there were 77 orphan drug designations granted for 64 compounds between 1983 and 2013.

The first orphan drug designations granted in 1986 was for guanethidine monosulfate and dimethyl sulfoxide, both of which were subsequently withdrawn. A majority of the designations were granted in 2011 (N=8).

There were 43% of designations granted for 23 different biologics based on drug classes, 36% for 27 different molecules, and 18% for others that represented 12 different compounds. The drug class of the designated compounds AI-RSA and Interleukin-1 Trap was unknown.

The biologics were broken down even further by researchers to include chimeric antibodies, human antibodies, humanized antibodies, unspecified antibodies, fusion proteins, and other biologics.

Between 1983 and 2013, 18% of orphan drug designations received FDA approval representing 13 different compounds, because canakinumab was approved for 2 indications.

In 1998, the first approved orphan drug for Sjögren’s syndrome was pilocarpine hydrochloride to help treat xerostomia and keratoconjunctivitis in these patients.

The standard deviation from designation to approval was 3.9 (2.81) with a range of 1 to 12 years. When divided by drug classes, 43% of the approved orphan drugs comprised small molecules, while 57% of FDA orphan drug approvals were biologics. The time between designation and approval for biologics was similar to small molecules.

The findings from the study show that in the last 30 years, 14 orphan drug programs were approved. Although the rarity and diversity of these conditions are reflective of the small sizes, all but 1 pivotal study included randomized controlled trials.