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 adversarial impact resulted in hospitalization, life-threatening occasions, and in some circumstances demise. Extreme hypocalcemia could 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 accredited in 2010 as a remedy for osteoporosis in postmenopausal ladies at excessive threat of fracture. The drug works by binding to a protein key to the operate and survival of cells concerned within the pure course of during 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 threat just isn’t. This complication was amongst these listed on the drug’s authentic 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 overview of Amgen’s longer-term testing of its osteoporosis drug.

The black field warning comes after an FDA overview of Facilities for Medicare & Medicaid Companies research discovered that remedy with Prolia led to a big enhance within the threat of growing extreme hypocalcemia in comparison with bisphosphonates, an older class of osteoporosis medication. The FDA stated the complication sometimes 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 the FDA Adversarial Occasion Report System database.

The FDA stated sufferers taking Prolia ought to preserve enough 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 contemplate Prolia’s hypocalcemia threat within the context of different osteoporosis medication out there.

Final yr, Prolia accounted for $2.9 billion in income within the 9 months ending Sept. 30, based on 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 Prescribed 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 accredited the remedy as a remedy for sickle cell illness. Vertex set a $2.2 million value for the one-time remedy, the identical value it costs within the sickle cell illness indication. It would compete in opposition to Bluebird Bio’s Zynteglo, the $2.8 million gene remedy accredited in 2022 for treating beta thalassemia.

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

Japanese authorities accredited 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 the earth for this drug.

—The European Fee accredited 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 out there 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 Prescribed drugs’ drug/system mixture remedy for migraine, citing manufacturing points, Satsuma mother or father 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 system 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 medical trial. Evaluation of the trial knowledge discovered issues with the system and the best way sufferers had been utilizing it. Satsuma modified the system and ran one other Part 3 research.

—Manufacturing points had been additionally accountable 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 plentiful on cancerous abdomen cells.

Photograph by FDA