In patients with knee osteoarthritis, intra-articular injections of 100 micrograms sprifermin led to significant benefits in measures of lateral femorotibial cartilage loss and joint space narrowing in a double-blind, randomized, proof-of-concept trial.
But the study failed to meet its primary efficacy endpoint – a significant change in central medial femorotibial compartment cartilage thickness at 6 and 12 months on MRI, reported Dr. Stefan Lohmander of Lund University, Sweden, and his associates.
Reasons for the preferential effect on the lateral compartment were unclear, the investigators said. The medial compartment is more severely affected in osteoarthritis, which might limit the effectiveness of anabolic agents that target cartilage, they said. Higher loading of the medial compartment in patients with varus also might "overwhelm" attempts to regenerate cartilage or slow loss, they added.
Dr. Stefan Lohmander
Preclinical studies indicated that sprifermin (recombinant human fibroblast growth factor 18) binds to and specifically activates fibroblast growth factor receptor 3 in cartilage to stimulate chondrocyte proliferation, cartilage matrix formation, and cartilage repair in vitro and in vivo.
The researchers randomized 192 patients with knee osteoarthritis to intra-articular injections of placebo or single or multiple-ascending doses of intra-articular sprifermin at 10, 30, or 100 micrograms (Arthritis Rheumatol. 2014 April 17 [doi:10.1002/art.38614]).
At 12 months, patients treated with 100 micrograms sprifermin had lost significantly less total femorotibial cartilage (difference from placebo, 0.04 mm; P = .039) and lateral femorotibial compartment cartilage (difference from placebo, 0.08 mm; P = .032), and had improved joint space narrowing of the lateral femorotibial compartment (difference from placebo, 0.52 mm; P = .012).
The study identified no significant difference in serious adverse events, treatment-emergent adverse events, or acute inflammatory reactions. All groups improved on the Western Ontario McMaster Universities Osteoarthritis Index, but the difference was relatively small, said Dr. Lohmander and his associates. The study did not collect detailed symptom data, patients were allowed to use pain medications, and patients knew which dose cohort (single or multiple) they were in – all of which limited interpretability of patient-reported data, the investigators noted.
The study was funded by Merck Serono S.A., a subsidiary of Merck KGaA in Darmstadt, Germany. Dr. Lohmander and three coauthors reported receiving consulting fees from Merck Serono, and two coauthors reported former employment with the company.