After missing a key secondary endpoint for its big osteoporosis drug romosozumab last fall and then running into a disturbing safety issue two months ago, Amgen $AMGN said Sunday that the FDA has handed the big biotech a rejection on its marketing application, a widely anticipated setback for the drug developer that will give rival Radius a shot at establishing a big lead in what had once been thought of as a horse race. And within hours of the CRL news from Amgen, Radius put out the word that it is making a change at the helm, with longtime CEO Bob Ward out and Novo US president Jesper Høiland stepping in to orchestrate the campaign for Radius’ first market launch.
According to the company’s statement, the agency says they want Amgen to include the data from two late-stage studies – the ARCH study as well as a Phase III in men called the BRIDGE trial, significantly delaying a comeback. That’s also bad news for UCB, which is partnered with Amgen.
BRIDGE was completed more than a year ago. I asked a spokesperson why the data hadn’t already been supplied to the FDA, and she said in reply that the executive crew at Amgen would offer some added context during their earnings review July 25.
In a followup on Monday afternoon, Amgen added: “Based on original discussions with FDA, the FRAME study was sufficient for initial BLA submission. The pivotal 7,180-patient FRAME trial was the first to evaluate vertebral fracture risk reduction as early as one year as a primary endpoint.”
Romo — which targets the sclerostin protein — followed by Amgen’s Prolia (denosumab) clearly vaulted the bar in Phase III for reducing vertebral fractures, with a hefty 75% risk reduction compared to a placebo plus denosumab. Investigators also were able to show a better safety profile in its presentation at the annual confab of the American Society for Bone Mineral Research. And there was an increase in bone mineral density among the drug arm in the study.
But the drug also missed a key secondary endpoint in the pivotal program. The drug did not significantly improve patients’ risk of non-vertebral fractures, leaving Radius Health $RDUS with a possible distinct advantage on that score after winning approval in late April. Then in May, Amgen presaged the rejection with a note spelling out a disturbing cardio risk imbalance between romo and Fosamax; 2.5% for romo and 1.9% for Fosamax.
Regulators made it clear they wanted to evaluate the full set of data in sizing up an approval, derailing an expected summer OK.
The board at Waltham, MA-based Radius offered Ward a slap on the back and congratulations for organizing the IPO and Tymlos approval. Chairman Kurt Graves also made it clear that the company wanted to go with an experienced hand at jump-starting new drug brands, giving Høiland a cheer for his work in that field at Novo.
While both Amgen and Radius have angled for an approval, commercial success is a completely different issue. As The New York Times reported recently, patients are generally started on bisphosphonates like Fosamax, which are old and cheap. But they’re also limited, unable to build bone the way Forteo and the two new drugs are designed to do.
Lilly, meanwhile, has been rapidly jacking up the price of Forteo ahead of its loss of patent protection. The Times reports the wholesale price has soared to $3,100 a month, more than three times its price in 2010. Lilly has been increasing the price twice a year, for six years.
Amgen has had its ups and downs over the past year. Parsabiv was approved earlier this year, but isn’t expected to become a blockbuster. A Phase III CGRP migraine drug – now partnered with Novartis – has done well, but so have other rival therapies that have been crowding in. It’s had more success in the courts, but still faces an ongoing legal brawl with Regeneron and Sanofi over the PCSK9 market, while neither group has been able to gain much traction with payers. Going back to the drawing board on romo won’t help, but can’t be avoided as the drug faces an uncertain future.
“During our interactions with the FDA, we agreed that the ARCH data should be considered in the regulatory review prior to the initial marketing authorization and, as a result, anticipated this request. We look forward to working through the review process with the Agency,” said Sean Harper, executive vice president of R&D at Amgen. “We remain committed to helping patients with osteoporosis and will use the additional time to better understand the benefit:risk profile of Evenity.”
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