Janssen‘s new under-the-skin formulation of daratumumab, called Darzalex Faspro, has been recommended for approval in Europe by the Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency, as a faster and easier alternative to treat people with multiple myeloma.
The new formulation, combining daratumumab and hyaluronidase, is given to patients by a healthcare provider as an abdominal injection that takes a few minutes. It is seen as an equally effective option to the original formulation, Darzalex, which requires an into-the-vein (intravenous) infusion given over several hours.
CHMP’s recommendation is for all four myeloma indications for which Darzalex is currently approved, including for patients who are newly diagnosed and for those given prior therapies.
Indications for patients with newly diagnosed myeloma include a combination of Revlimid (lenalidomide), and dexamethasone, or Velcade (bortezomib), melphalan, and prednisone for people who cannot receive a stem cell transplant; and a combination with Velcade, thalidomide, and dexamethasone for those able to undergo stem cell transplant.
Darzalex Faspro is also recommended for use in combination with Velcade and dexamethasone, or Revlimid and dexamethasone, for patients who received at least one previous therapy; and as a single agent for patients who failed at least one proteasome inhibitor and an immunomodulatory agent.
“Despite therapeutic advances in the treatment of multiple myeloma, the time taken for administration of most intravenous treatments is relatively long and there have been few significant improvements over the years,” Maria-Victoria Mateos, MD, PhD, director of the myeloma unit at University Hospital of Salamanca-IBSAL, Spain, said in a press release.
“The daratumumab subcutaneous formulation has the potential to transform the treatment experience for patients and physicians as it reduces time in the chair from hours to minutes, and, because it is administered as a fixed dose from the first treatment, it reduces preparation time and chances of error by eliminating the need for dose calculations,” Mateos added.
CHMP’s recommendation was based on the findings from two ongoing clinical trials: the multicenter and randomized COLUMBA Phase 3 trial (NCT03277105), and the multicenter and open-label PLEIADES Phase 2 trial (NCT03412565).
COLUMBA enrolled 522 people with relapsed or refractory myeloma who had tried at least three lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who failed to respond to both types of therapy.
The goal was to compare the two daratumumab formulations to find out if Darzalex Faspro was similar to Darzalex in safety, response rates, time to disease worsening or death, and overall survival.
Results showed that the proportion of patients responding to treatment and the time lived without disease worsening was also similar in both groups. However, fewer patients receiving Darzalex Faspro experienced infusion-related reactions (13%) compared to those on Darzalex (35%).
Also, patients were treated with Darzalex Faspro over a median injection time of five minutes, while those on Darzalex required a median of seven hours to receive the first infusion, 4.3 hours for the second, and 3.4 hours for subsequent infusions.
PLEIADES is also investigating the efficacy of Darzalex Faspro, but as a combination therapy and in a range of myeloma patients. These include combinations with Velcade, melphalan, and prednisone in newly diagnosed patients, and with Revlimid and dexamethasone in relapsed or refractory patients.
In these two populations, response rates were close to 90% and combinations were safe and well-tolerated. Lung infections were the most common side effect in the Velcade group, while fatigue, diarrhea, infections, fever, constipation, and shortness of breath were the most commonly reported in the Revlimid group.
“Since its first European approval in 2016, intravenous daratumumab has been used in the treatment of more than 100,000 patients worldwide and, if approved, both new and existing patients with multiple myeloma will be able to start or switch to the subcutaneous formulation as part of their multiple myeloma daratumumab-based treatment regimens,” said Craig Tendler, MD, vice president of oncology clinical development and global medical affairs at Janssen.
“Today’s Positive Opinion represents Janssen’s commitment to continuing to improve the treatment experience for patients living with multiple myeloma,” he added.
Darzalex Faspro was recently approved by the U.S. Food and Drug Administration as a 1,800 mg fixed dose by subcutaneous injection for four of the six indications for which Darzalex is approved in the U.S. For more information on specific indications, click here.
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