The European Commission (EC) has granted orphan drug designation to RA101495 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
RA101495 is a synthetic macrocyclic peptide inhibitor of complement component C5.
Ra Pharmaceuticals is developing RA101495 as a self-administered, subcutaneous injection for the treatment of PNH, refractory generalized myasthenia gravis, and lupus nephritis.
RA101495 binds complement C5 with subnanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative, or lectin pathways.
RA101495 also directly binds to C5b, disrupting the interaction between C5b and C6 and preventing assembly of the membrane attack complex.
According to Ra Pharmaceuticals, repeat dosing of RA101495 in vivo has demonstrated “sustained and predictable” inhibition of complement activity with an “excellent” safety profile.
The company also said phase 1 data have suggested that RA101495 is potent inhibitor of C5-mediated hemolysis with a favorable safety profile.
Preclinical research involving RA101495 was presented at the 2015 ASH Annual Meeting, and phase 1 data were presented at the 21st Congress of the European Hematology Association earlier this year.
RA101495’s orphan designation
The EC grants orphan designation to therapies intended to treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
In situations where there is already an approved standard of care—such as with PNH, where the monoclonal antibody eculizumab (Soliris) is currently available—the EC requires companies developing a potential orphan drug to provide evidence that the drug is expected to provide significant benefits over the standard of care.
In the case of RA101495, the decision to grant orphan designation was based on the potential for improved patient convenience with subcutaneous self-administration, as well as the potential to treat patients who do not respond to eculizumab.
Orphan designation provides the company developing a drug with regulatory and financial incentives, including protocol assistance, 10 years of market exclusivity once the drug is approved, and, in some cases, reductions in fees.
