(Reuters) - Merck & Co said it will seek U.S. approval next year for its long-delayed experimental osteoporosis drug, odanacatib, after it proved effective in a late-stage trial but was associated with rare thigh-bone fractures seen with standard treatments.
The once-weekly pill, deemed a potential blockbuster product by some industry analysts, significantly reduced risk of fractures of the hip and spine, and of non-vertebral fractures, compared with placebo, Merck said on Monday.
The trial, called LOFT, involved almost 17,000 women, 65 years or older, who had been diagnosed with the bone-thinning disease that primarily affects postmenopausal women.
Although the overall rate of side effects was similar in the two patient groups, those taking odanacatib had slightly higher incidence of death and atrial fibrillation, a type of irregular heartbeat that can cause stroke.
There were similar numbers of cardiovascular events in both patient groups, although a numerically higher incidence of strokes in the odanacatib group was not deemed statistically significant.
Five patients taking odanacatib developed atypical fractures of the thigh-bone, compared with none in the placebo group.
Similar rare femur fractures have been among the most worrisome side effects of the leading class of treatments, called bisphosphonates, which include Merck’s own Fosamax and generic forms of it sold by others.
Keith Kaufman, a senior Merck research official, said all patients who developed the thigh fractures had encountered some form of trauma and had severe osteoporosis. By contrast, he said many such fractures associated with bisphosphonates have been “spontaneous.”
Kaufman noted that certain skin lesions occurred more often in patients taking odanacatib, than those in the placebo group, but said the condition went away or moderated after treatment was stopped.
“The safety profile (of odanacatib) has some red flags” which could create concern among regulators, BMO Capital Markets analyst Alex Arfaei said in a research note. Even so, he said odanacatib’s benefits appear to outweigh its risks.
Arfaei predicted the drug will be approved by early 2016 and have sales of $536 million in 2020.
In a late-stage trial whose results were described in 2012, odanacatib demonstrated effectiveness in preventing fractures, boosting Wall Street hopes that the new type of osteoporosis treatment would be approved and eventually generate annual sales of up to $2 billion.
Merck initially planned to seek marketing approval in the first half of 2013. But the company early last year said it would delay its filing until 2014 because of certain “safety issues” that needed to be resolved in an ongoing extension of the LOFT study.
Kaufman said the marketing application has now been delayed again, until 2015, “to collect additional long-term data” on the relative benefit and risk of odanacatib.
Odanacatib works by blocking cathepsin K, an enzyme involved in the body’s natural process of resorbing bone.
Merck shares closed down 3 cents at $59.52 Monday on the New York Stock Exchange.
Reporting by Ransdell Pierson; Editing by Meredith Mazzilli, Bernard Orr