Side effect fears weigh on Merck osteoporosis drug

Positive efficacy data for Merck’s osteoporosis drug candidate odanacatib have been undermined by doubts about safety and a decision to hold back filing of the drug until mid-2015.

Merck (known as MSD outside the US) unveiled the results of the pivotal phase 3 outcomes trial of the once-weekly cathepsin K inhibitor yesterday, showing that it met its primary objective by reducing the risk of vertebral fractures by 54% and hip fractures by 47% compared to placebo.

Overall, the risk of having a vertebral fracture was reduced by 72% while the risk of non-vertebral fractures dropped by 23% in the LOFT study, which experts said indicated at least comparable efficacy to other osteoporosis drugs on the market.

The fly in the ointment for Merck however was a slightly higher incidence of atrial fibrillation (AF) in the treatment group compared to placebo, which was accompanied by a small but non-significant increase in strokes which could attract the attention of regulators.

There were also a handful of cases in the odanacatib group of thigh-bone fractures that are a recognised side effect of the older bisphosphonate class of osteoporosis drugs, with none reported for placebo.

Odanacatib has long been considered one of the brightest prospects in Merck’s pipeline – eclipsed only by cancer candidate Keytruda (pembrolizumab) – but has been a long time getting through development with a number of delays setting back its filing date, originally scheduled for early 2013.

The latest timeline represents a further delay for the project, which had been expected to be submitted before the end of the year.

Since 2012 peak sales forecasts seem to have been trimmed back, in part because of increasing competition in osteoporosis with the loss of patent protection for Eli Lilly’s Evista (raloxifene) and the launch of rival in-patent drugs such as Amgen’s Prolia (denosumab), which saw sales in the first half of the year rise nearly 40% to $460m.

As a once-weekly oral product, odanacatib has been expected to make strong in-roads into the osteoporosis market, two years ago a number of analysts suggesting sales of $3bn or more at peak. Now they seem a little more cautions, with some suggesting $1bn is achievable and others predicting half that amount or less.

Merck remains bullish on the drug’s prospects however, and Keith Kaufman, the firm’s vice president for diabetes and endocrinology clinical research, said the LOFT data “support a favourable benefit/risk profile for odanacatib.”

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