Soliris biosimilar drug Bkemv found to have equivalent safety, efficacy
New trial data show biosimilar is interchangeable with brand name product
Bkemv (eculizumab-aeeb) — a biosimilar of Soliris (eculizumab) that was approved in the U.S. earlier this year as a treatment for paroxysmal nocturnal hemoglobinuria (PNH) — shows equivalent safety and efficacy to its reference drug, according to newly published data from a Phase 3 clinical trial.
Results from that study, called DAHLIA (NCT03818607), also showed that Amgen’s Bkemv is an interchangeable biosimilar, meaning a switch between the two products did not affect the safety or effectiveness of treatment.
DAHLIA’s full data, detailed in a study titled “Comparative clinical efficacy and safety of biosimilar ABP 959 and eculizumab reference product in patients with paroxysmal nocturnal hemoglobinuria,” had supported the therapy’s approval for PNH in the U.S. and Europe — where it’s sold as Bekemv. That study now has been published in the American Journal of Hematology.
“This relatively large study population of adult patients with PNH who were stable on [Soliris] treatment was determined to be an appropriate and homogeneous [comparable] study population in terms of expected response to … treatment to provide the essential information required,” the researchers wrote. “The results presented in this study add to the totality of scientific evidence of no clinical difference between [Bkemv] and [Soliris].”
DAHLIA trial tested Bkemv biosimilar drug in patients on Soliris
In PNH, the abnormal activation of the complement cascade, a part of the immune system, leads to the destruction of red blood cells, called hemolysis. This, in turn, results in a deficiency of these cells, or anemia, and symptoms such as fatigue, shortness of breath, and abdominal pain.
Soliris is a therapy long approved to reduce hemolysis in PNH patients. Its active ingredient, eculizumab, is an antibody that blocks the C5 complement protein, thereby suppressing the activation of the complement system.
As a biosimilar of Soliris, Bkemv, previously known as ABP 959, contains the same active ingredient as its reference drug and shows comparable quality, safety, and efficacy.
Because biosimilars typically don’t need to undergo clinical testing as comprehensive as that supporting the approval of the reference medication, they are usually available at lower prices.
Amgen launched the DAHLIA trial in 2019 to evaluate whether Bkemv had comparable safety and efficacy to Soliris when treating adults with PNH. A total of 42 patients, with a mean age of 50.2, were recruited at several sites in the U.S. and Europe. All were on stable treatment with Soliris.
The participants were randomly assigned to either receive Bkemv for one year followed by Soliris for six months (20 patients), or start with Soliris and then change to Bkemv (22 patients). Each treatment was given as a 900 mg dose via intravenous or into-the-vein injection, every two weeks.
The trial met its primary goal of showing no clinically meaningful differences between the two treatments in controlling hemolysis, as measured by blood levels of a hemolysis marker called lactate dehydrogenase (LDH).
This comparable efficacy was further confirmed in secondary measures. These included stable levels of complement activity, hemoglobin — the protein in red blood cells that carries oxygen — and bilirubin, another marker of hemolysis, that were comparable between both groups. Also comparable were the levels of red blood cells susceptible to complement-mediated destruction over time.
The therapies also showed equivalent pharmacological properties and immunogenicity, or the ability to promote the production of anti-drug antibodies (ADAs), which bind to the medication. Some of these ADAs may have neutralizing properties, reducing the therapy’s effect.
Specifically, two patients (9.1%) in the Soliris-to-Bkemv group tested positive for ADAs following the switch to Bkemv. However, this positivity was temporary and not associated with any serious adverse effects. No patient in either group tested positive for neutralizing ADAs.
Study IDs no new safety concerns with Bkemv despite more adverse events
In terms of safety, at least one adverse event was reported by 33 of the 41 patients who received at least one dose of Bkemv (80%), and by 39 of the 42 who received one or more doses of Soliris (92.9%).
Most events were considered mild to moderate in severity and mainly included infections and infestations (about 50% of patients) and infusion site reactions (about 36%).
Hemolysis occurred in two patients (4.9%) during Bkemv treatment and in four (9.5%) during Soliris treatment.
Overall, seven patients (17.1%) experienced 14 serious adverse events during Bkemv treatment, including heart failure, gallbladder inflammation, gastroenteritis, and anemia, while two patients (4.8%) experienced anemia and heart failure during Soliris treatment.
Although serious adverse events were more frequent with Bkemv, “these events were determined to be either [influenced] by other factors or are events known to occur in the PNH population,” the researchers wrote.
[Analyses did not identify] any new safety concerns or new patterns of [serious adverse events].
Further analyses did not identify “any new safety concerns or new patterns of [serious adverse events]; therefore, these numeric differences were not conclusive of a difference in the safety profile between [Bkemv and Soliris],” the team wrote.
“The results of this study … along with previously demonstrated similarity of analytical, nonclinical, and clinical [pharmacological properties] in healthy volunteers support a demonstration of no clinically meaningful differences between [Bkemv] and [Soliris],” the researchers concluded.
About the Author
