Rilonacept is a recombinant biological active pharmaceutical ingredient and a dimeric fusion protein that acts as an interleukin-1 cytokine trap. It consists of ligand-binding portions of the human interleukin-1 receptor component (IL-1R1) and interleukin-1 receptor accessory protein (IL-1RAcP), linked to the Fc portion of human IgG1. Rilonacept binds and neutralizes IL-1α and IL-1β, thereby inhibiting IL-1-mediated inflammatory signaling.
Rilonacept is identified by CAS No. 501081-76-1, FDA UNII 8K80YB5GMG, and molecular weight of approximately 251 kDa. It is produced using recombinant Chinese hamster ovary (CHO) cells.
Unlike conventional small-molecule APIs, Rilonacept is a complex recombinant protein. Therefore, conventional small-molecule parameters such as melting point, specific rotation, residue on ignition and simple HPLC assay are not appropriate primary quality specifications for the intact biological drug substance.
Rilonacept is an IL-1 inhibitor and recombinant fusion protein. It functions as a soluble decoy receptor that binds IL-1α and IL-1β and prevents their interaction with cell-surface IL-1 receptors.
The current U.S. ARCALYST prescribing information describes Rilonacept as approximately 251 kDa and expressed in recombinant CHO cells. The finished product is supplied as a sterile white to off-white lyophilized powder.
| Parameter | Details |
|---|---|
| Product Name | Rilonacept |
| Synonyms | IL-1 Trap, Interleukin-1 Trap, IL-1-TRAP, KPL-914 |
| CAS Number | 501081-76-1 |
| FDA UNII | 8K80YB5GMG |
| DrugBank | DB06372 |
| ATC Code | L04AC04 |
| API Class | Recombinant fusion protein / biological API |
| Molecular Type | Dimeric Fc-fusion protein |
| Molecular Weight | Approximately 251 kDa |
| Expression System | Recombinant CHO cells |
| Protein Components | IL-1R1 ligand-binding domain + IL-1RAcP + human IgG1 Fc |
| Target | IL-1α and IL-1β |
| Mechanism | Soluble IL-1 cytokine trap |
| Appearance | White to off-white lyophilized powder |
| Reconstituted Appearance | Clear, colorless to pale-yellow viscous solution |
| Finished Product Concentration | 80 mg/mL after reconstitution |
| Reconstituted pH | 6.5 |
| Dosage Form | Lyophilized powder for solution for injection |
The FDA label confirms the approximately 251 kDa molecular weight, CHO expression system, lyophilized appearance, 80 mg/mL reconstituted concentration and pH 6.5.
Rilonacept is used as an interleukin-1 inhibitor in inflammatory and autoinflammatory diseases.
Rilonacept is indicated for the treatment of recurrent pericarditis and reduction in the risk of recurrence in adults and pediatric patients 12 years and older.
Rilonacept is indicated for treatment of cryopyrin-associated periodic syndromes (CAPS), including:
These indications apply to adults and children 12 years and older under the current U.S. indication.
Rilonacept is also indicated for maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) in adults and pediatric patients weighing 10 kg or more.
Rilonacept requires a biological-product quality-control strategy rather than the conventional testing approach used for small-molecule APIs.
The EMA assessment report states that Rilonacept drug-substance specifications include controls for appearance, identification, strength, potency, purity and impurities.
The EMA specifically states that Rilonacept drug-substance specifications include appearance, identification, strength, potency, purity and impurities. Public regulatory documents do not provide a complete set of numerical acceptance limits for every CMS field above.
For Rilonacept, appropriate analytical characterization can include:
These tests are more scientifically appropriate for Rilonacept than conventional small-molecule API tests such as melting point or residue on ignition.
Rilonacept manufacturing requires recombinant protein production using a suitable mammalian expression system followed by purification, formulation and extensive biological characterization.
The FDA identifies recombinant CHO cells as the production system for Rilonacept.
Important manufacturing and quality controls include:
The EMA assessment concluded that the proposed Rilonacept drug-substance specifications covered the relevant quality attributes, including appearance, identity, strength, potency, purity and impurities.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| pH (1% Solution) | 6.5 |