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Abaloparatide approved · 'Bone Up'

• 0:00
  Hello and welcome to Bone Up, the podcast all
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  about bones, how we make them, why we break them
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  and if we fully understand them. I'm David Armstrong.
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  Hi and I'm Richie Abel and over this series we're
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  going to be exploring osteoporosis, bones, what
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  we know and what we're yet to discover and we
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  hope you will join us on the journey. So for
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  anyone keen to learn more about our infrastructure
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  of calcified collagen, this is bone up hello
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  and welcome to a special mini episode of bone
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  up We had a mini episode last year, Richie, when
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  we were able to talk about a new drug, romacizumab.
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  And like London buses, you don't get a new drug
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  for 10 years and then two come along at once
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  because we're here today to talk about abaloperatide,
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  which has been approved for use in the UK just
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  within the last week. So exciting times in the
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  world of osteoporosis treatments. The whole bone
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  research field just seems to go from strength
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  to strength, and it's resulting in a lot of new
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  treatments for patients. I guess for you listeners
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  at home, the most important question you might
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  want to get the answer to today is, what are
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  the treatment guidelines for Avaloparatide? Well,
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  the UK's National Institute for Clinical Excellence,
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  NICE, have issued a statement just within the
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  last week saying that they... Recommend the baloperitide
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  for patients who are at very high risk of fracture.
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  Postmenopausal women at very high risk of fracture.
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  Very high risk is defined, of course, according
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  to the FRAC score and the NOG guidance as patients
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  who are at least 60 % above the treatment threshold.
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  And in practical terms at the clinic, that's
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  usually patients who've had new vertebral fractures.
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  Because we know from, well, almost all the podcasts
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  we've done in the last few years, that there's
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  a lot of focus now on new vertebral fractures
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  as identifying patients at really high risk who
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  we want to treat as quickly and as early as possible
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  with the strongest possible drug. So that's what
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  we're looking at here. We're looking at a sort
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  of a high end drug for the worst patients, which
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  is great news. If you prescribe a patient then.
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  How will they take the drug and how long will
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  they take it for? Well, this is one of the red
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  list medicines. In other words, you have to come
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  to the hospital to get it and be supervised by
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  a consultant. It's an injectable treatment like
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  many new medicines. You will inject yourself
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  with it once a day for 18 months. If that sounds
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  rather like teriparatide that you inject for
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  24 months and romosuzumab that you inject for
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  12 months, well then it fits very much into the
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  paradigm in that area. And after you've finished
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  the 18 -month treatment, then you will have to
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  switch to one of the other drugs, to one of the
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  anti -resorptive drugs which prevents bone loss.
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  So David, you have a lot of treatments available
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  to you now to discuss and to prescribe to your
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  patients. How do you think Abalaparatide is going
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  to fit into the clinic? Have NICE been able to
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  give any information about the organization and
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  funding etc? No I think that's something that
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  many of us as sort of UK bone experts are talking
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  about and are working on at the moment. And we
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  will need to see just how it fits into the clinic.
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  There's no doubt that there has been a paradigm
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  shift in the last three to five years on how
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  we deal with very high risk patients. And lots
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  of clinics now will have been set up with fast
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  track clinics and clinics just for vertebral
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  fractures to get these patients in and get them
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  seen. So it will no doubt sit alongside teriparatide
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  and rumosuzumab for those groups of patients.
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  It doesn't have to be kept in the fridge. That
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  might offer some advantages to some groups of
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  patients. And as I say, the course lasts for
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  18 months rather than 12 or 24. And that may
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  influence some choice as well. There's some suggestion
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  that you may not get just as high calcium levels
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  in the blood as you get sometimes as a side effect
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  with teriparatide. But apart from those sort
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  of feelers, we're really not just quite certain
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  yet how it will fit in. how it will be funded
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  in different areas. But, you know, that's a nice
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  thing to be able to talk about. It's good fun
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  to be able to talk about how we get a new drug
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  to the patients and how we get funding for it.
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  Much better that than having, you know, having
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  no new drugs available. I sort of mentioned there
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  briefly in passing about drugs that sort of build
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  bone, drugs that remove bone. Just remind us
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  where this sort of drug fits then in that category.
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  Richie, is this a drug that builds bone or a
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  drug that removes bone? A balaparotide is classed
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  as an anabolic agent, which means that it builds
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  bone. The simple explanation is that a balaparotide
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  improves bone mineral density and bone mass by
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  stimulating bone cells. And obviously, if you
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  improve density and mass, a bone is going to
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  be better able to resist a fracture when somebody
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  has a triple fall. complex explanation is that
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  abalaparotide works by mimicking a natural hormone
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  in our bodies. And that's parathyroid hormone.
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  Parathyroid hormone is very important for regulating
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  calcium in our bodies. So you can see straight
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  away how this hormone is going to be important
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  for a disease like osteoporosis, which is fundamentally
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  a loss of calcium and a loss of bone. And basically
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  the medicine will travel to a patient's bone
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  cells bind with receptors on the cell surface,
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  like a docking station. And once a baliparotide
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  docks with a bone cell, it will trigger a set
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  of chemical reactions inside the cell that stimulate
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  its activity. And regular listeners, you'll know
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  that there's two really important types of bone
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  cells, osteoblasts, which form new bone, and
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  osteoclasts, which resorb old and damaged bone.
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  And normally in a healthy adult, the osteoclasts
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  take away the damaged bone, the old bone and
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  the osteoblasts replace it. And in somebody with
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  osteoporosis, there's an imbalance. The osteoclasts
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  take away too much bone and the osteoblasts don't
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  put back enough. Well, abalaparatide resets that
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  imbalance by stimulating the osteoblast cells
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  a lot more than the osteoclast cells. And in
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  their clinical trials, when they tested the drug,
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  They measured biomarkers in the blood to see
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  how big that effect was. What they reported is,
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  is that abaloparatide increases osteoblastic
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  bone formation markers by about 80%, and the
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  bone resorption markers are only increased by
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  about 20%. By improving the formation over the
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  resorption, you get a net gain in bone mineral
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  density and bone mass, which is... essentially
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  what's going to prevent the fractures. That's
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  exciting and I find patients love to hear how
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  drugs actually work because as much as anything
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  it's an incentive to persevere with the drug
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  if you understand how it's working. That of course
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  is okay in the laboratory or at the science level.
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  We have evidence that it actually works of course
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  in humans and that it does increase bone mineral
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  density. and that it does reduce fracture. Isn't
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  that right? If you follow these things, there
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  was a study published, it must be maybe seven,
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  eight years ago now, called the ACTIV study,
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  which specifically compared abaloparatide to
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  patients who weren't getting any drug and also
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  looked at some patients getting teriparatide.
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  Do you want to let us know just the headline
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  findings from that in terms, Richie? Did it work
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  in terms of reducing fractures? So the headline
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  then is that the treatment greatly reduced the
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  chance of a postmenopausal woman with osteoporosis
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  sustaining a fracture. The people recruited into
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  the trial were all women between 49 and 86 years
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  old. They were all defined as being at high risk.
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  Essentially, like you were saying earlier, they
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  had very low bone mineral density and they'd
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  either suffered a fracture or they were over
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  65 years old. And as you say, the drug was compared
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  to a placebo. The study showed that in the balaparotide
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  patients, they increased their bone mineral density
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  by about 12 % in the lumbar vertebrae. and about
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  4 % at the hip in comparison to the patients
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  who didn't take any treatment. And this was associated
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  with a really big reduction in the risk of fracture.
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  The patients who took a balaparatide had about
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  an 88 % reduction in the risk of fracture in
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  the vertebrae and about a 69 % reduction in risk
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  of a major osteoporotic fracture. And of course,
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  that includes fractures like hip fractures. which
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  are the ones which really devastate lives and
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  cause a lot of death. Great results from the
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  trial. You need to get back to us then in six
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  months or 12 months to see where this will actually
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  fit into your clinics. Some of the great things
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  that have happened in the last few years in terms
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  of osteoporosis treatment have allowed us to
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  develop these fast -track clinics where we get
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  patients with vertebral fractures in as quickly
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  as possible to get them new drugs. So it's great
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  that we have those sort of clinics and those
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  sort of channels already set up where people
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  are getting teriparatide or romosuzumab or sometimes
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  denosumab. So those are already set up. I'm quite
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  certain abaloparatide will fit into that clinic.
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  Exactly where it fits in yet, I don't think we're
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  absolutely certain. How it will compare with
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  teriparatide or romosuzumab, I don't think we're
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  absolutely certain. But we're certainly excited
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  about this and we're excited to see the benefits
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  that it will offer patients. Brilliant. We better
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  leave it there. Thank you for joining, listeners.
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  Bye -bye. See you in the next episode. Bye now.