SAN DIEGO — Intra-articular injections of a protein drug derived from fibroblast growth factor-18 in patients with knee osteoarthritis (OA) led to increases in mean cartilage thickness within the joint after two years, although no significant change in symptom scores was seen, a researcher said here.
At the highest dose of the drug, called sprifermin, mean total MRI-measured cartilage thickness in the knee joint increased by 0.03 mm at the year 2 evaluation, whereas patients receiving placebo injections had a loss of 0.02 mm in cartilage thickness, said Marc Hochberg, MD, of the University of Maryland School of Medicine in Baltimore.
Other radiologic measures of joint structure also showed a significant benefit for sprifermin at the higher dose, Hochberg said at a late-breaking session at the American College of Rheumatology annual meeting. But the same downward trajectory was seen in scores on the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scale for all treatment groups including placebo.
Hochberg noted that the phase II study is planned to extend for 5 years, and said the investigators still hold out hope that clinical symptoms will improve with sprifermin in these later years. He also pointed out that patients were permitted to take pain medications during the study, which could have masked clinical effects from the drug during this initial portion of the study.
In the trial, approximately 550 patients were randomized to receive placebo or one of four doses of sprifermin, in injections given three times over a week, repeated every 6 months through month 18. Sprifermin dosing groups were 30 mcg per cycle every 12 months; 30 mcg per cycle every 6 months; 100 mcg per cycle every 12 months; or 100 mcg per cycle every 6 months. To maintain blinding, the 12-month sprifermin groups received placebo injections at months 6 and 18.
Median patient age was about 65, and 70% were female. OA was graded at Kellgren-Lawrence level 2 in roughly 70%; the rest were at grade 3. Mean WOMAC score at baseline was about 40.
At the end of year 2, WOMAC scores declined by 18 to 22 points in all groups, with no significant differences or any trends worth noting.
However, the trial technically succeeded because its prespecified primary endpoint was change in total knee joint cartilage thickness, and all secondary endpoints except for WOMAC score were also radiologic assessments of cartilage thickness and joint space width.
On those measures, the two higher sprifermin doses did very well (Results with the 30-mcg doses, whether patients received two or four cycles, did not differ markedly from placebo).
Highly significant differences from the placebo group were seen in the two 100-mcg dosing groups for MRI-measured medial and lateral tibiofemoral cartilage thickness, both overall and in the central subregions of these cartilage compartments. Medial and lateral minimum joint space width, as measured by x-ray, also significantly favored the high-dose sprifermin groups.
The high-dose groups did experience higher rates of acute inflammatory responses: 22% and 23% for those receiving four and two cycles of 100 mcg, respectively, compared with 13.5% for placebo. All of these occurred in the first cycle, Hochberg said, and none led to study dropout. In all other respects, rates of adverse events of various kinds were the same in all groups, he reported.
Sprifermin’s developer, Merck KGaA of Darmstadt, Germany, said it was “highly encouraged” by the study results, but stopped short of promising a phase III trial.
The study was sponsored by Merck KGaA. Co-authors included employees of EMD Serono, a unit of Merck KGaA.
Hochberg disclosed relevant relationships with Bioiberica, Bristol Myers-Squibb, EMD Serono, Galapagos, IBSA, Eli Lilly, Novartis, Pfizer, Plexxikon, Samumed, Theralogix, and TissueGene.