Posted by Jeff Berk; BOLT International
Now that I write a blog I get a lot more emails than ever before. My favorites are from patients who we either connected to some of BOLT’s thought leaders for treatment, or else gave them something to discuss with their physicians. I get about one a day of these, and they’re really gratifying stories (thanks guys). I also get some from other people, not pharma people but patients, who attribute the most ridiculous adverse events to their being on one of the drugs that they read about. Something like: “I started to take Mirena. The next week I lost my job at the Department of Motor Vehicles”. In such a case, sensitive person that I am, I try to respond in a way that doesn’t hurt my emailer’s feelings. But I bet even they didn’t want her coming into work looking like this. Do ya think that just maybe getting fired wasn’t an adverse effect of the drug? Maybe being on birth control isn’t the same thing as a license to be a completely irresponsible ^%$#@. Just sayin’. Finally, I get emails from people telling me either that they don’t like my snide non-pharma comments (too bad. stop being offended by everything), or even more to the point, they don’t like my pharma comments. Now that offends ME! HaHa. Just kidding. I’m the grown-up in the room. So long as you take out the profanity, post it to the blog and I’ll let it through.
So a couple of weeks ago I got another email, from a lady who WAS a blog subscriber. She took one administration of Prolia (denosumab) and said that it caused “side effects from my first (and last) injection of Prolia”. I guess I wasn’t sufficiently sympathetic (I was dubious of her tale of woe, but I don’t claim to have all the facts), so she dumped the BOLT Pharma Blog. Jokes on you, nameless ex-blog reader; as here’s another tidbit from BOLT’s Osteoporosis Thought Leader Panel, published this past June:
AMG-785 / CDP7851 (Amgen / UCB )
- The introduction of AMG-785 will give Amgen the first opportunity to capture the high risk patients early by treating to lower fracture risk with monthly or eventually quarterly doses of AMG-785, and then switching them to a long-term maintenance regimen of denosumab twice yearly. Amgen is just starting a Ph-III trial for osteoporosis. It will include 8,000 – 9,000 patients. There is a 1-year trial, presumably with bone mineral density (BMD) as an endpoint but Amgen has expressed the expectation that they will also see a fracture reduction. We do not know if fractures are a primary or secondary endpoint. The extension phase of this trial will clearly have fracture endpoints as the primary. Together there will be short-term and long term safety. Based on current status, this puts the US registration for AMG-785 at late 2015/early 2016.
“When you are talking about Amgen starting a phase III is that for bone healing or is that an actual osteoporosis trial? That is a relatively traditional osteoporosis trial. Well it is two studies by the way and they run at the same time with 8000 or 9000 patients. They are very similar, but that is because they have been pushed by FDA to do them that way. And part of that is running for one year and part of that study is running for a longer period of time. So they will get the first safety data from the one year? Yeah. I think that they expect because it is so potent that they can see the effect of the fractures within a year. So they do the two studies also from a safety point of view. So if they start that January 2012 then the theory would be regardless of what happens with the fracture healing trial the earliest that we have a registration for use of antisclerostin in osteoporosis would be say early or mid-2015? That is about three years. End of 2015, beginning of 2016, something like that”.
I guess the other thing about teriparatide is that it is not particularly patient friendly. It is daily injections and you have really got to have a motivated patient to do that whereas if you go with an antisclerostin monoclonal antibody then potentially saying to a patient we would like to attack that and then how often do you give that antibody, but it is certainly not every day. If they haven’t gone into phase III year we don’t quite know how often they are going to give it. But in their fracture healing they are giving perhaps three or four doses over three months or something like that. Yeah, I was wondering if they were going to go to like a once a quarter kind of dosing? I did say that it is something they are actively considering at the moment but I am just recalling that they had just published in JBMR their effects after a single dose of antibody, and I think from what I was recall there extending out a number of months that we are seeing stimulation of bone formation markers. I do say they will be thinking carefully about what the data should be. I think suggesting to someone that, look, we will give you a subcutaneous injection every three months for the first year and then we will give you an infusion of zoledronic acid and that will hold you for a year or two years after you have had that infusion after you have those course of injections; that is a very easy regimen for doctor and patient alike. So I guess we will need to wait and see how much it costs. But I can see that being really quite attractive. I agree with you. I think if you have got someone who hasn’t had a fracture and their T-score is -2.6 or something then maybe just giving bisphosphonate alone is sensible but people who are presenting with fractures and they have got a FRAX score, particularly elderly people, so somebody who is 80 and has got a FRAX risk or hip fracture risk of 5 percent or something then I would agree that a more aggressive up front approach makes a lot more sense”.