Romosozumab

Last updated

Romosozumab
Monoclonal antibody
Type Whole antibody
Source Humanized (from mouse)
Target Sclerostin
Clinical data
Trade names Evenity
Other namesAMG 785, romosozumab-aqqg
AHFS/Drugs.com Monograph
MedlinePlus a619026
License data
Pregnancy
category
  • AU:B3
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C6452H9926N1714O2040S54
Molar mass 145877.58 g·mol−1
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Romosozumab, sold under the brand name Evenity, is a medication used to treat osteoporosis. [7] [8] It has been found to decrease the risk of fractures of the spine. [7]

Contents

Common side effects include headache, joint pain, and injection site reactions including pain. [7] It may increase the risk of heart attacks, strokes, and deaths from cardiovascular disease. [7] It is a humanized monoclonal antibody that targets sclerostin. [9] Research shows the drug increases bone formation and decreases bone resorption in postmenopausal women with low bone density. Romosozumab was approved for medical use in Japan, the United States and the European Union in 2019. [7] [10] [11]

The US Food and Drug Administration (FDA) considers it to be a first-in-class medication. [12]

Medical uses

Romosozumab is used for osteoporosis to decrease the risk of fractures. [10] Two trials found that it reduced the rate of vertebral fracture. In one, there was a 73% lower risk of vertebral fracture after one year, and the benefit was maintained after a second year of taking denosumab. In the other, one year of romosozumab followed by one year of alendronate had a 50% vertebral fracture reduction compared to two years of alendronate. [10]

Side effects

Common side effects include headache, joint pain, and injection site reactions including pain. [7]

In one trial, more patients in the romosozumab group had serious cardiovascular events compared to the alendronate group (0.8% vs 0.3%), [13] though this was not found in a trial of romosozumab vs placebo. [14] Currently, the drug contains a FDA boxed warning on its labeling stating that it may increase the risk of heart attack, stroke and cardiovascular death and should not be used in patients who have had a heart attack or stroke within the previous year. [7] Such a limitation does not exist in Japan. [15] In a large real-world study, prescription of romosozumab was associated with less adverse cardiovascular events compared to other osteoanabolic therapies. [16]

History

Romosozumab was approved for medical use in Japan in January 2019, [10] the United States in April 2019 [10] and the European Union in December 2019. [11]

It was originally discovered by Chiroscience, [17] which was acquired by Celltech (now[ when? ] owned by UCB). [18] Celltech entered in a partnership with Amgen in 2002 for the product's development. [19]

The UK's National Institute for Health and Care Excellence (NICE) decided to recommend romosozumab for use in England and Wales. [20]

Related Research Articles

<span class="mw-page-title-main">Osteoporosis</span> Skeletal disorder

Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in fracture risk. It is the most common reason for a broken bone among the elderly. Bones that commonly break include the vertebrae in the spine, the bones of the forearm, the wrist, and the hip. Until a broken bone occurs there are typically no symptoms. Bones may weaken to such a degree that a break may occur with minor stress or spontaneously. After the broken bone heals, the person may have chronic pain and a decreased ability to carry out normal activities.

<span class="mw-page-title-main">Parathyroid hormone</span> Mammalian protein found in humans

Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.

<span class="mw-page-title-main">Bisphosphonate</span> Pharmaceutical drugs for preventing bone loss

Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they have two phosphonate groups. They are thus also called diphosphonates.

<span class="mw-page-title-main">Teriparatide</span> Pharmaceutical drug for treating osteoporosis

Teriparatide, sold under the brand name Forteo, is a form of parathyroid hormone (PTH) consisting of the first (N-terminus) 34 amino acids, which is the bioactive portion of the hormone. It is an effective anabolic agent used in the treatment of some forms of osteoporosis. Teriparatide is a recombinant human parathyroid hormone analog. It has an identical sequence to the 34 N-terminal amino acids of the 84-amino acid human parathyroid hormone.

<span class="mw-page-title-main">Alendronic acid</span> Chemical compound

Alendronic acid, sold under the brand name Fosamax among others, is a bisphosphonate medication used to treat osteoporosis and Paget's disease of bone. It is taken by mouth. Use is often recommended together with vitamin D, calcium supplementation, and lifestyle changes.

<span class="mw-page-title-main">Raloxifene</span> Chemical compound

Raloxifene, sold under the brand name Evista among others, is a medication used to prevent and treat osteoporosis in postmenopausal women and those on glucocorticoids. For osteoporosis it is less preferred than bisphosphonates. It is also used to reduce the risk of breast cancer in those at high risk. It is taken by mouth.

<span class="mw-page-title-main">Zoledronic acid</span> Chemical compound

Zoledronic acid, also known as zoledronate and sold under the brand name Zometa among others, by Novartis among others, is a medication used to treat a number of bone diseases. These include osteoporosis, high blood calcium due to cancer, bone breakdown due to cancer, Paget's disease of bone and Duchenne muscular dystrophy (DMD). It is given by injection into a vein.

<span class="mw-page-title-main">Osteopenia</span> Medical condition

Osteopenia, known as "low bone mass" or "low bone density", is a condition in which bone mineral density is low. Because their bones are weaker, people with osteopenia may have a higher risk of fractures, and some people may go on to develop osteoporosis. In 2010, 43 million older adults in the US had osteopenia. Unlike osteoporosis, osteopenia does not usually cause symptoms, and losing bone density in itself does not cause pain.

<span class="mw-page-title-main">Gemtuzumab ozogamicin</span> Pharmaceutical drug

Gemtuzumab ozogamicin, sold under the brand name Mylotarg, is an antibody-drug conjugate that is used to treat acute myeloid leukemia.

<span class="mw-page-title-main">Sclerostin</span> Protein-coding gene in the species Homo sapiens

Sclerostin is a protein that in humans is encoded by the SOST gene. It is a secreted glycoprotein with a C-terminal cysteine knot-like (CTCK) domain and sequence similarity to the DAN family of bone morphogenetic protein (BMP) antagonists. Sclerostin is produced primarily by the osteocyte but is also expressed in other tissues, and has anti-anabolic effects on bone formation.

<span class="mw-page-title-main">Ibandronic acid</span> Chemical compound

Ibandronic acid is a bisphosphonate medication used in the prevention and treatment of osteoporosis and metastasis-associated skeletal fractures in people with cancer. It may also be used to treat hypercalcemia. It is typically formulated as its sodium salt ibandronate sodium.

<span class="mw-page-title-main">Denosumab</span> Human monoclonal antibody

Denosumab, sold under the brand names Prolia and Xgeva among others, is a human monoclonal antibody used for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone.

<span class="mw-page-title-main">Strontium ranelate</span> Chemical compound

Strontium ranelate, a strontium(II) salt of ranelic acid, is a medication for osteoporosis marketed as Protelos or Protos by Servier. Studies indicate it can also slow the course of osteoarthritis of the knee. The drug is unusual in that it both increases deposition of new bone by osteoblasts and reduces the resorption of bone by osteoclasts. It is therefore promoted as a "dual action bone agent" (DABA).

<span class="mw-page-title-main">Lasofoxifene</span> Chemical compound

Lasofoxifene, sold under the brand name Fablyn, is a nonsteroidal selective estrogen receptor modulator (SERM) which is marketed by Pfizer in Lithuania and Portugal for the prevention and treatment of osteoporosis and for the treatment of vaginal atrophy, and the result of an exclusive research collaboration with Ligand Pharmaceuticals (LGND). It also appears to have had a statistically significant effect of reducing breast cancer in women according to a study published in The Journal of the National Cancer Institute.

Senile osteoporosis has been recently recognized as a geriatric syndrome with a particular pathophysiology. There are different classification of osteoporosis: primary, in which bone loss is a result of aging and secondary, in which bone loss occurs from various clinical and lifestyle factors. Primary, or involuntary osteoporosis, can further be classified into Type I or Type II. Type I refers to postmenopausal osteoporosis and is caused by the deficiency of estrogen. While senile osteoporosis is categorized as an involuntary, Type II, and primary osteoporosis, which affects both men and women over the age of 70 years. It is accompanied by vitamin D deficiency, body's failure to absorb calcium, and increased parathyroid hormone.

<span class="mw-page-title-main">Clodronic acid</span> Chemical compound

Clodronic acid (INN) or clodronate disodium (Na2CH2Cl2O6P2) (USAN) is a first generation (non-nitrogenous) bisphosphonate. It is an anti-osteoporotic drug approved for the prevention and treatment of osteoporosis in post-menopausal women and men to reduce vertebral fractures, hyperparathyroidism, hypercalcemia in malignancy, multiple myeloma and fracture related pain because of its anti-inflammatory effects shown as a reduction in inflammatory markers like IL-1β, IL-6, and TNF-α.

<span class="mw-page-title-main">Medication-related osteonecrosis of the jaw</span> Medical condition

Medication-related osteonecrosis of the jaw is progressive death of the jawbone in a person exposed to a medication known to increase the risk of disease, in the absence of a previous radiation treatment. It may lead to surgical complication in the form of impaired wound healing following oral and maxillofacial surgery, periodontal surgery, or endodontic therapy.

Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such as hot flashes, accelerated skin aging, vaginal dryness, decreased muscle mass, and complications such as osteoporosis, sexual dysfunction, and vaginal atrophy. They are mostly caused by low levels of female sex hormones that occur during menopause.

Abaloparatide, sold under the brand name Tymlos among others, is a parathyroid hormone-related protein (PTHrP) analog medication used to treat osteoporosis. It is an anabolic agent.

Recombinant human parathyroid hormone, sold under the brand name Preotact among others, is an artificially manufactured form of the parathyroid hormone used to treat hypoparathyroidism. Recombinant human parathyroid hormone is used in the treatment of osteoporosis in postmenopausal women at high risk of osteoporotic fractures. A significant reduction in the incidence of vertebral fractures has been demonstrated. It is used in combination with calcium and vitamin D supplements.

References

  1. "2.4. Romosozumab". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 21 May 2024.
  2. "AusPAR: Romosozumab". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 21 May 2024.
  3. "Evenity Product information". Health Canada. 25 April 2012. Retrieved 29 May 2022.
  4. "Summary Basis of Decision (SBD) for Evenity". Health Canada . 23 October 2014. Retrieved 29 May 2022.
  5. "Evenity- romosozumab-aqqg injection, solution". DailyMed. 30 April 2020. Retrieved 21 May 2024.
  6. "Evenity EPAR". European Medicines Agency (EMA). 9 December 2019. Retrieved 21 May 2024.
  7. 1 2 3 4 5 6 7 "FDA approves new treatment for osteoporosis in postmenopausal women at high risk of fracture". U.S. Food and Drug Administration (FDA) (Press release). 9 April 2019. Retrieved 12 April 2019.
  8. "Drug Trials Snapshot: Evenity". U.S. Food and Drug Administration (FDA). 26 May 2021.
  9. "Statement On A Nonproprietary Name Adopted By The USAN Council: Romosozumab" (PDF). American Medical Association. Archived from the original (PDF) on 29 September 2012.
  10. 1 2 3 4 5 Kaplon H, Muralidharan M, Schneider Z, Reichert JM (2020). "Antibodies to watch in 2020". mAbs. 12 (1): 1703531. doi:10.1080/19420862.2019.1703531. PMC   6973335 . PMID   31847708.
  11. 1 2 Rees V (13 December 2019). "EC approves treatment for severe osteoporosis postmenopausal women". European Pharmaceutical Review. Retrieved 27 February 2020.
  12. "New Drug Therapy Approvals 2019". U.S. Food and Drug Administration (FDA). 31 December 2019. Retrieved 15 September 2020.
  13. Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, et al. (October 2017). "Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis". The New England Journal of Medicine. 377 (15): 1417–1427. doi: 10.1056/nejmoa1708322 . hdl: 2158/1094968 . PMID   28892457. S2CID   205102366.
  14. Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, et al. (October 2016). "Romosozumab Treatment in Postmenopausal Women with Osteoporosis". The New England Journal of Medicine. 375 (16): 1532–1543. doi: 10.1056/nejmoa1607948 . PMID   27641143.
  15. Stokar J, Szalat A (20 May 2024). "Response to Letter to the Editor From Kawaguchi: "Cardiovascular Safety of Romosozumab vs PTH Analogs for Osteoporosis Treatment: A Propensity Score Matched Cohort Study"". The Journal of Clinical Endocrinology & Metabolism. doi:10.1210/clinem/dgae348. ISSN   0021-972X.
  16. Stokar J, Szalat A (March 2024). "Cardiovascular Safety of Romosozumab vs. PTH Analogs for Osteoporosis Treatment: a Propensity Score Matched Cohort Study". The Journal of Clinical Endocrinology and Metabolism. doi: 10.1210/clinem/dgae173 . PMID   38482603.
  17. Quested T (7 June 2015). "Cream of life science entrepreneurs' first venture was selling doughnuts". Business Weekly. Cambridge, England: Q Communications. Retrieved 24 December 2018.
  18. Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, et al. (December 2003). "Osteocyte control of bone formation via sclerostin, a novel BMP antagonist". The EMBO Journal. 22 (23): 6267–6276. doi:10.1093/emboj/cdg599. PMC   291840 . PMID   14633986.
  19. "Celltech group Interim Report 2002" (PDF). Celltech Group plc.
  20. {{cite web | vauthors = NICE (2022) | date = 25 May 2022 | work = Evening Standard | url = https://www.nice.org.uk/guidance/ta791/chapter/1-Recommendations}