Amgen’s expectations for romosozumab take a hit as Radius lines up its rival osteoporosis drug Amgen has helped shore up expectations for its osteoporosis drug romosozumab, releasing updated Phase III data that underscore its straight shot at a marketing approval. But the big biotech, which is partnered on this program with UCB, may have to concede a big piece of this competitive market after spelling out its failure on a key secondary 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, which recruited 7,180 high-prism postmenopausal women. But the drug missed a key secondary endpoint, which may cost Amgen dearly. The drug did not significantly improve patients’ risk of non-vertebral fractures, leaving Radius Health — which has posted an 86% risk reduction in vertebral fractures — with a possible distinct advantage on that score. As Leerink’s Geoffrey Porges has noted, payers are acutely aware of the cost of hip fractures in this patient population, a non-vertebral sector that appears to be a clear positive for Radius Health $RDUS. The fracture incidence rate in this group was 1.6% for Amgen’s drug group compared to 2.1% for the placebo plus denosumab. Amgen tried to rationalize the shortfall in non-vertebral fractures, pointing to a particular data set as a possible culprit. But Porges wasn’t all that impressed. He noted: Even in this post hoc analysis, at 12 months while the RRR for hip fractures fell 59%, the p value was only 0.12 – leaving us to question whether romosozumab has much clinical benefit at all in non-vertebral fractures. Radius’s Phase III drug abaloparatide, in a group of parathyroid hormone analog drugs that includes Eli Lilly’s Forteo, may get to duke it out with the pharma giant, Porges adds. The sclerostin drugs, including Lilly’s experimental blosozumab, may have to settle for approvals restricted to reducing the risk of vertebral fractures. Analysts’ peak sales projections for these drugs have been all over the map. Deutsche Bank last year pegged abalo’s peak at $1.1 billion, though they believed that romo would come out on top as the better drug with a bigger market share, depending on how the generics shake out. While both Amgen and Radius stand a good chance of winning an approval, commercial success is a completely different issue. As The New York Times reported recently, patients are generally started on bisphosphanates 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 that 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.
FRAME Phase III trial of UCB/Amgen’s romosozumab (osteoporosis) has been presented. While detailed data give some comfort over the lack of a significant effect on more clinically important non-vertebral fractures, we continue to view the drug's clinical differentiation and market opportunity as uncertain. With the drug likely to launch with a disadvantaged label and with safety concerns likely to hamper initial uptake. We believe detailed data from the FRAME study will give some comfort over the drug’s possible benefits on more clinically important fractures. However, a supportive post hoc analysis, which excluded close to 50% of all recruited patients, falls short of being fully convincing in our view and is unlikely to impact the drug’s approved label. This leaves Amgen/UCB dependent on a more robust outcome from the ARCH head-to-head study due in 1H 2017 to support the drug's clinical differentiation. Physicians we have spoken to have been skeptical of the drug’s positioning given that alternative options have more robust evidence to support benefits in most clinically important fractures. Feedback from physicians also suggests that expectations that approval of new anabolic drugs will drive a significant market expansion are too optimistic given reimbursement access challenges. As a result, we view previous bull case scenarios for sales of $2-3bn as unlikely to be achieved. We assume ~$1bn in peak sales at an 80% probability (1) Compelling benefit on vertebral fractures confirmed; (2) 25% reduction in non-vertebral fractures missed statistical significance (p=0.096). This may have been impacted by a lower than expected event rate (2.1% placebo rate vs expected 3.5%); (3) Lack of benefit in Latam region may have limited the trials ability to demonstrate a benefit on non-vertebral fractures. A more meaningful 42% reduction was seen elsewhere. While this and the numerical reduction in non-vertebral fractures is encouraging, physicians at the conference have been skeptical of the validity of a post hoc analysis which required almost half of recruited patients to be excluded; (4) Romo was associated with a numerical reduction in hip fractures (0.2% vs 0.4%; 46% reduction); (5) Physicians remain nervous about the drug’s safety given cases of osteonecrosis of the jaw and an atypical fracture. We note the ONJ rate of ~1 in 1,800 patients is 5x that seen in a recent cohort of bisphosphonate users. We expect the severity and implications of these cases to be a subject of close regulatory scrutiny by the FDA, leaving a timely approval still less than certain
actually in latin america the nonvertebral fracture rate was HIGHER in the romo arm than in placebo !!! -- gee you mean if we ignore those patients the drug looks better in the other ones ? Dad - I got straight A's on my report card Julie - How can that be you got an F in math and a D in history Dad the test frequency in those classes was too low, ignore those grades - look I got an A in PE and Art !! Congratulations Julie once I knew to ignore the bad grades... wow you do have straight A's
romo is an nfl color commentator now. Amgen’s drug is headed for a deny or approval with severe restrictions.
Laid off depending on the scenario. Either scenario will result in a layoff, just a matter of how large it will be
