Roche Laboratories and GlaxoSmithKline's Boniva (ibandronate sodium)

Osteoporosis is a disease of the bonesthat results in loss of bone mass andstructural breakdown of bone tissue,which ultimately leads to bone weaknessand an increased risk of fractures.Osteoporosis, or "porous bones," affects~10 million Americans, of whom 8 millionare women. Also, an estimated 34million Americans have low bone mass,placing them at elevated risk for osteoporosis.¹ The disease is mostly asymptomatic,and diagnosis may not be determineduntil a sudden incident causes afracture. Some symptoms associatedwith osteoporosis include severe backpain or stooped posture.¹

Current therapies for the preventionand treatment of osteoporosis include bisphosphonates,estrogen therapy, selectiveestrogen receptor modulators, calcium,and vitamin D supplementation.¹ RocheLaboratories released ibandronate sodium(Boniva) tablets in 2003 for the managementof postmenopausal osteoporosis.In January 2006, the FDA approvedBoniva for injection, a once-quarterlyintravenous injection for the treatment ofpostmenopausal osteoporosis.

Pharmacology

Boniva is a bisphosphonate and worksby inhibiting osteoclast activity, whichresults in a reduction in bone resorption.In postmenopausal women, it reducesbone turnover and may cause anincrease in bone mass.²

Clinical Trials

An early clinical trial examined thesafety and efficacy of intravenous ibandronatesodium for the prevention ofpostmenopausal osteoporosis.The multicenter,randomized, double-blind, placebo-controlled trial included ~630 postmenopausalwomen. Patients received adose of either ibandronate 0.5 mg, 1 mg,or 2 mg, or placebo, intravenously every3 months. The primary outcome was themean change in bone mineral density(BMD) of the lumbar spine, comparedwith baseline. Results demonstrated adose-dependent increase in BMD for thepatients receiving active drug therapy.Increase in BMD from baseline for the0.5-, 1-, and 2-mg groups were standarddeviations 1, 1.8, and 2.5, respectively (P= .001). Those receiving placebo therapyhad a decrease in BMD of 0.4 (P = .001).³

The Dosing Intravenous Administration(DIVA) study compared 2 different intravenousibandronate regimens with itsoral dosage form. The multicenter, randomized,double-blind, noninferiority trialincluded ~1400 women and took placeover a 2-year period. Treatment groupsincluded intravenous ibandronate 2 mgevery 2 months, 3 mg every 3 months, ororal ibandronate 2.5 mg daily. All womenreceived supplemental calcium and vitaminD throughout the trial. DIVA comparedthe efficacy, safety, and tolerabilityof the different treatment arms, with theprimary end point being the meanchange of lumbar spine BMD from baselineat 1 year, with a noninferiority marginof 1%. Results after 1 year of therapydemonstrated an increased percentagechange in lumbar spine BMD from baselinein the 2-and 3-mg injection groupsversus oral therapy (3.8%, 5.1%, and4.8%, respectively, P = .001). Two-yearfindings included increased lumbar BMDmore so with the intravenous dosinggroups than the oral dosing group—6.4% and 6.3% with 2 and 3 mg, respectively,and 4.8% with oral ibandronate(P <.001).⁴

Safety

The most common adverse eventswith ibandronate include arthralgia, backpain, abdominal pain, hypertension, andinfluenza-like symptoms.² Intravenousibandronate is eliminated renally andtherefore should not be given to anypatient with a creatinine clearance lessthan 30 mL/min. No dose adjustmentsare necessary in patients with hepaticimpairment. Hypocalcemia and hypovitaminosisD must be treated prior to startingibandronate injection, and it is recommendedto continue supplementationduring therapy.² Ibandronate is in pregnancycategory C and should only beused in pregnancy only if the potentialbenefit outweighs the risk to the fetus.

Outlook

Boniva injection can be used to treatosteoporosis in postmenopausal womenwho may have compliance problemswith their current oral regimen. The recommendeddose of Boniva injection is 3mg every 3 months administered over aperiod of 15 to 30 seconds and must beadministered by a health care professional.²

Dr. Soo is a senior research pharmacistwith the Investigational DrugService at Brigham and Women'sHospital, Boston, Mass. Nolan Cookis a sixth-year PharmD candidatefrom Massachusetts College ofPharmacy currently on clinical clerkshipin the Investigational DrugService at Brigham and Women'sHospital.

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