Amgen Osteoporosis Drug Prolia Is Hit With FDA’s Strictest Warning

A blockbuster Amgen drug for osteoporosis now carries the FDA’s strictest warning that its use can result in dangerously low ranges of calcium within the blood.

This complication, hypocalcemia, is a specific threat for sufferers with superior kidney illness, the black field warning states. In these sufferers, this antagonistic impact resulted in hospitalization, life-threatening occasions, and in some circumstances loss of life. Extreme hypocalcemia may be asymptomatic however signs the FDA warned that sufferers and physicians ought to look ahead to embody confusion, irregular coronary heart rhythm, fainting, muscle spasms, and weak point.

Prolia, a monoclonal antibody administered each six months as a subcutaneous injection, was first accepted in 2010 as a remedy for osteoporosis in postmenopausal girls at excessive threat of fracture. The drug works by binding to a protein key to the perform and survival of cells concerned within the pure course of wherein bone is damaged down and absorbed by the physique. Lowering this bone resorption is meant to extend bone mass and energy.

Whereas the black field warning is new, the hypocalcemia threat just isn’t. This complication was amongst these listed on the drug’s unique label. Approval of Prolia got here with a Danger Analysis and Mitigation Technique, an FDA program that imposes strict oversight of a drug to protect in opposition to security issues. The FDA additionally required Amgen to conduct extra medical testing to additional assess security.

In 2022, the FDA issued an alert stating it’s investigating the danger that Prolia might trigger extreme hypocalcemia in sufferers with superior kidney illness that requires dialysis remedy. That alert stemmed from the continued assessment of Amgen’s longer-term testing of its osteoporosis drug.

The black field warning comes after an FDA assessment of Facilities for Medicare & Medicaid Companies research discovered that remedy with Prolia led to a big improve within the threat of creating extreme hypocalcemia in comparison with bisphosphonates, an older class of osteoporosis medicine. The FDA stated the complication usually developed two to 10 weeks following every Prolia injection, with the best threat throughout weeks two to 5. The company additionally reviewed 25 circumstances submitted by means of the FDA Hostile Occasion Report System database.

The FDA stated sufferers taking Prolia ought to preserve sufficient calcium and vitamin D consumption. For these with superior kidney illness, the FDA advises frequent monitoring of calcium ranges within the blood. The FDA additionally stated clinicians ought to take into account Prolia’s hypocalcemia threat within the context of different osteoporosis medicine accessible.

Final 12 months, Prolia accounted for $2.9 billion in income within the 9 months ending Sept. 30, in response to Amgen’s most up-to-date monetary report. Amgen additionally sells a newer osteoporosis drug referred to as Evenity, although hypocalcemia has additionally been reported in sufferers handled with this product. Various osteoporosis therapies embody Eli Lilly’s Forteo and Tymlos from Radius Well being. The labels of all of those merchandise carry black field warnings that flag numerous security dangers.

Right here’s a recap of different latest regulatory information:

—Vertex Prescription drugs gene remedy Casgevy landed FDA approval as a remedy for the uncommon blood illness beta thalassemia. This approval comes about six weeks after the company first accepted the remedy as a remedy for sickle cell illness. Vertex set a $2.2 million worth for the one-time remedy, the identical worth it fees within the sickle cell illness indication. It can compete in opposition to Bluebird Bio’s Zynteglo, the $2.8 million gene remedy accepted in 2022 for treating beta thalassemia.

—Authorities in Japan accepted AstraZeneca drug danicopan as a brand new remedy for paroxysmal nocturnal hemoglobinuria (PNH), a uncommon blood dysfunction wherein the complement system assaults pink blood cells. The oral drug can be marketed underneath the model identify Voydeya. AstraZeneca already markets the PNH medicine Soliris and Ultomiris, each of which work by blocking a complement system protein referred to as C5. Voydeya addresses a unique protein referred to as issue D.

Japanese authorities accepted Voydeya as an add-on remedy for sufferers whose illness just isn’t sufficiently addressed by a C5 inhibitor. The approval is the primary wherever on this planet for this drug.

—The European Fee accepted a subcutaneously injected model of Roche most cancers immunotherapy Tecentriq. The drug, which blocks the checkpoint protein PD-L1 on most cancers cells, has been accessible as an intravenous infusion that takes between 30 and 60 minutes. Roche stated the subcutaneous model will take between 4 and eight minutes.

—The FDA turned down Satsuma Prescription drugs’ drug/system mixture remedy for migraine, citing manufacturing points, Satsuma dad or mum firm Shin Nippon Biomedical Laboratories introduced. Satsuma’s product candidate, STS101, is a dry powder formulation of the outdated migraine drug dihydroergotamine. It’s administered by way of an intranasal system meant to deliver sufferers quicker ache aid.

The FDA full response letter is the newest in a string of setbacks for Satsuma. In 2020, STS101 failed a Part 3 medical trial. Evaluation of the trial knowledge discovered issues with the system and the way in which sufferers have been utilizing it. Satsuma modified the system and ran one other Part 3 research.

—Manufacturing points have been additionally responsible for the FDA rejection of zolbetuximab, an Astellas Pharma drug developed for treating gastric or gastroesophageal junction adenocarcinoma. The antibody drug is on the entrance of a aggressive pack of drug candidates designed to focus on claudin 18.2, a protein ample on cancerous abdomen cells.

Picture by FDA