The FDA has turned down Amgen’s marketing application for osteoporosis candidate romosozumab, asking for new data that could delay any approval significantly.
As expected, the US regulator wants to see data from the recently-completed ARCH trial of the anti-sclerostin antibody added into the marketing application, along with the results of the BRIDGE study in men with osteoporosis, which means the application will have to be re-filed.
The FDA’s complete response letter (CRL) does not come out of the blue as Amgen and its partner UCB have had a couple of knock-backs with romosozumab, which has the proposed trade name Evenity.
Last year, the drug hit its main target of reducing vertebral fractures in the FRAME study, but was unable to reduce non-vertebral fracture, a key secondary endpoint. Then in May the ARCH trial showed a reduction in both vertebral and non-vertebral fractures – albeit with a much stronger effect on the former – but also revealed that more patients on romosozumab than the comparator drug (alendronate) had cardiovascular side effects.
In the wake of those developments Amgen and UCB had already said they would no longer be able to get approval for romosozumab this year as data from the new trials would have to be considered by the FDA, while analysts at Leerink said it was likely the drug’s use would be restricted if it was approved at all.
As it stands, the drug is also under regulatory review in Canada and Japan, while UCB has said it plans to submit a marketing application in Europe in the latter half of this year.
While anticipated the delay to romosozumab is more good news for Radius Health, which claimed US approval for its Tymlos (abaloparatide) drug for osteoporosis in April on the strength of robust data, including an 86% reduction in new vertebral fractures and a 43% cut in non-vertebral fractures.
Tymlos is a parathyroid hormone-related protein (PTHrP) analogue that competes most closely with Eli Lilly’s ageing osteoporosis drug Forteo (teriparatide) and could become a $1bn-plus product at peak, according to some analysts although others are less optimistic.
Forteo is heading for patent expiry, so Radius’ new drug will have to contend with a market disrupted by generic competition to the older brand, although its prospects were lifted after Merck & Co decided to drop its once-weekly cathepsin K inhibitor odanacatib last year.
Amgen and UCB still have a lead in the anti-sclerostin category however, after main rival Eli Lilly was first to push development of its blosozumab candidate from Phase II to phase I trials last year because of formulation challenges.