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 danger 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 might be asymptomatic however signs the FDA warned that sufferers and physicians ought to look ahead to embrace 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 therapy for osteoporosis in postmenopausal ladies at excessive danger of fracture. The drug works by binding to a protein key to the perform and survival of cells concerned within the pure course of through which bone is damaged down and absorbed by the physique. Decreasing this bone resorption is meant to extend bone mass and energy.
Whereas the black field warning is new, the hypocalcemia danger isn’t. This complication was amongst these listed on the drug’s unique label. Approval of Prolia got here with a Threat 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 further scientific testing to additional assess security.
In 2022, the FDA issued an alert stating it’s investigating the chance that Prolia could trigger extreme hypocalcemia in sufferers with superior kidney illness that requires dialysis therapy. That alert stemmed from the continuing 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 therapy with Prolia led to a big improve within the danger of creating extreme hypocalcemia in comparison with bisphosphonates, an older class of osteoporosis medication. The FDA mentioned the complication usually developed two to 10 weeks following every Prolia injection, with the best danger throughout weeks two to 5. The company additionally reviewed 25 circumstances submitted by way of the FDA Antagonistic Occasion Report System database.
The FDA mentioned sufferers taking Prolia ought to keep 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 mentioned clinicians ought to think about Prolia’s hypocalcemia danger within the context of different osteoporosis medication 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 known as Evenity, although hypocalcemia has additionally been reported in sufferers handled with this product. Different osteoporosis therapies embrace 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 current regulatory information:
—Vertex Prescription drugs gene remedy Casgevy landed FDA approval as a therapy for the uncommon blood illness beta thalassemia. This approval comes about six weeks after the company first accepted the remedy as a therapy for sickle cell illness. Vertex set a $2.2 million value for the one-time remedy, the identical value it fees within the sickle cell illness indication. It’s going to 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 therapy for paroxysmal nocturnal hemoglobinuria (PNH), a uncommon blood dysfunction through which the complement system assaults crimson blood cells. The oral drug shall be marketed beneath the model title Voydeya. AstraZeneca already markets the PNH medication Soliris and Ultomiris, each of which work by blocking a complement system protein known as C5. Voydeya addresses a unique protein known as issue D.
Japanese authorities accepted Voydeya as an add-on remedy for sufferers whose illness isn’t sufficiently addressed by a C5 inhibitor. The approval is the primary wherever on the earth 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 mentioned the subcutaneous model will take between 4 and eight minutes.
—The FDA turned down Satsuma Prescription drugs’ drug/machine mixture therapy for migraine, citing manufacturing points, Satsuma mum or dad 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 through an intranasal machine supposed to deliver sufferers quicker ache reduction.
The FDA full response letter is the most recent in a string of setbacks for Satsuma. In 2020, STS101 failed a Part 3 scientific trial. Evaluation of the trial information discovered issues with the machine and the best way sufferers had been utilizing it. Satsuma modified the machine and ran one other Part 3 examine.
—Manufacturing points had been additionally guilty 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
