SAN DIEGO – Oral salmon calcitonin significantly reduced pain and stiffness, improved physical function, and slowed cartilage loss, especially in the medial tibial compartment in a 2-year, placebo-controlled, phase III clinical trial involving 1,169 patients with painful knee osteoarthritis.
But the trial did not meet one of its primary end points, improvement in joint space width.
Even so, "this pivotal phase III clinical trial suggests that oral salmon calcitonin," dosed at 0.8 mg twice daily for 24 months, "is safe, and has sustained symptom-modifying" benefits in osteoarthritis and "some structure-modifying effects," said Dr. Morten Karsdal, CEO of Nordic Bioscience in Herlev, Denmark, which sponsored the trial and is developing the drug in collaboration with Novartis Pharma.
Oral calcitonin (oCT) holds the promise of offering the benefits of calcitonin – widely used for osteoporosis, among other problems – without the immunogenicity of currently available nasal and injectable formulations.
At month 24, 17% of the 585 oCT subjects had circulating antibodies against the drug; historically, 40%-70% of users develop antibodies against nasal and injectable formulations, Dr. Karsdal said.
The mean age of trial subjects was 64 years, and mean body mass index about 29 kg/m2; 68% were women. Most patients had Kellgren-Lawrence grade II disease, the rest were grade III. Rescue medication was allowed in both the placebo and treatment arms.
By month 24, oCT subjects demonstrated about a 5% loss in cartilage volume on MRI in both the signal and non-signal knee; placebo subjects demonstrated slightly more than a 7% loss in both knees. The differences were statistically significant.
"We prevent a decrease; we do not gain cartilage," Dr. Karsdal said.
Also at month 24, oCT bested placebo in WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index pain scores (–115.7 vs. –94.9 mm; P = .002), function scores (–338.7 vs. –283.0 mm; P = .013), and stiffness scores (–44.1 vs. –32.6 mm; P less than .001).
It took about 6 months of treatment before oCT began to clearly separate from placebo on the WOMAC pain score.
Oral calcitonin also beat placebo on 24-hour visual analog scale (VAS) pain scores (P = .018), patient global assessment (P = .008), and physician global assessment (P = .014).
The most common adverse events in the oCT group, vs. placebo, were hot flashes (18% vs. 4%), nausea (14% vs. 3%), dyspepsia (10% vs. 5%), and diarrhea (10% vs. 4%).
Almost 20% of oCT subjects dropped out of the trial because of those and other side effects; the drug-related discontinuation rate in the placebo arm was 6%.
The side effects "are associated with the mode of action of salmon calcitonin, and mostly happened early," Dr. Karsdal said.
The trial was sponsored by Nordic Bioscience, which is developing the drug in collaboration with Novartis Pharma. Dr. Karsdal is the CEO of Nordic Bioscience.