Romo in the approval Frame, but franchise won’t be built in a day

Beyond securing several key drug approvals Amgen has had a tough time of it, with sales of Repatha, Kyprolis, Blincyto and Imlygic so far disappointing the sellside. So it really needed the osteoporosis project romosozumab to show a benefit in its phase III Frame study.

On this score alone Amgen can this morning celebrate another positive hit. But, as with other potential blockbusters, Amgen has some way to go to build romo into a franchise, and in fact the data seem to have fallen short of some bullish expectations, explaining today’s surge in the stock of its osteoporosis rival Radius Health.

The Frame data were disappointing to the extent that romo missed secondary endpoints in preventing non-vertebral fractures at 12 and 24 months. And, though no signs of hearing loss were seen this time around, there were two cases of osteonecrosis of the jaw in the romo-treated group.

This is important because Radius’s abaloparatide did hit a non-vertebral fracture endpoint in phase III – and has avoided the jaw osteonecrosis side effects to boot; it was subsequently filed for approval in the EU. Radius rose 7% on Friday and opened up another 30% today, while Amgen stock was off 1%.

Positive

On the positive side for Amgen, romo met both of Frame’s co-primary endpoints, reducing vertebral fractures at 12 and 24 months, as well as improving 12-month clinical fracture incidence, a secondary measure.

No p values were provided, and while numerically the numbers look a little worse than Radius’s, across-trial comparisons are difficult. Radius has a much smaller dataset – 2,463 patients were recruited into its Active study versus Frame’s 7,180 – and treated them for 18 months versus Amgen’s 12.

The omens for Frame looked good after an open-label romo trial, Structure, read out positive last September, though some analysis remained cautious (Therapeutic focus – Osteoporosis antibodies approach key readouts, September 4, 2015). EvaluatePharma consensus figures see romo selling a conservative $287m in 2020.

In this month’s Amgen re-initiation Leerink wrote that romo could become a $1-2bn osteoporosis asset, but that safety was the key aspect to watch. Romo is also vital to the struggling Belgian group UCB, which acquired its discoverer, Celltech, after the latter had licensed it to Amgen.

Assault on Forteo

As part of a franchise that includes Amgen’s blockbuster Prolia, romo is part of an antibody assault on Lilly’s Forteo, a hormone analogue whose patent expires in two years.

Romo is an anti-sclerostin MAb that works by preventing the downregulation of osteoblastic bone formation. Other anti-sclerostin MAbs include Lilly’s own blosozumab, and Novartis/MorphoSys’s NOV-3, licensed to Mereo Biopharma as BPS-804 for the bone disease osteogenesis imperfecta.

Radius’s abaloparatide, meanwhile, is a synthetic peptide analogue of human parathyroid hormone-related protein, and is expected to post sales of over $500m in 2020. Radius plans a US filing by the end of the current quarter, and obviously needs to have a major partnership in place by the time abaloparatide is launched.

Amgen and UCB now plan to talk to regulators with a view to filing romo by the end of the year. As far as franchise-building goes, Amgen is likely to promote romo on the basis of a one-year course followed by Prolia – mirroring Frame’s design – so it is also positive that today’s data show vertebral fracture prevention over the Prolia and romo treatment periods.

However, like with Repatha, Amgen could find that with romo the generation of positive pivotal study data is just the beginning of the battle. And if Radius now signs up a big-hitting competitor, life for Amgen will get tougher still.

Project Company Study Design Trial ID
Abaloparatide Radius Health Active 2,463 pts, 18mths vs placebo or Forteo NCT01343004
Romosozumab Amgen/UCB Frame 7,180 pts, 1yr romosozumab then 1yr Prolia NCT01575834

To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com or follow @JacobPlieth on Twitter

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