New Under-the-skin Darzalex Formulation Approved in EU

The European Commission (EC) has approved a new under-the-skin (subcutaneous), fixed-dose formulation of Janssen’s Darzalex (daratumumab) for the treatment of adults with multiple myeloma.

The approval of the new type of delivery applies to all indications for which the therapy’s original intravenous (into-the-vein) formulation is currently approved. That includes its use with newly diagnosed patients and those who have received prior lines of therapy. This also means that people currently receiving intravenous Darzalex may now switch to the under-the-skin formulation if they choose.

With this new fixed-dose formulation, patients in the E.U. will now have access to an equally effective form of the medication that can be administered within a few minutes instead of hours. In addition, only the first dose of the new formulation needs to be given in an environment with available resuscitation facilities. That also will ease the treatment’s administration.

“This new formulation was specifically designed as the next step in enhancing the treatment experience with daratumumab, without compromising on safety or efficacy,” Patrick Laroche, MD, lead of Janssen’s hematology therapy area of Europe, the Middle East, and Africa (EMEA), said in a press release.

“Since its first launch, daratumumab has been used by more than 130,000 patients globally, and Janssen is pleased to expand our offering by making the subcutaneous formulation available for all previously approved indications,” Laroche added.

Darzalex is an antibody designed to recognize and block the activity of CD38, a protein found on the surface of myeloma cells, to prevent their growth and eliminate them. It was originally developed by Genmab, and then licensed to Janssen in August 2012.

The new formulation combines Darzalex’s active ingredient, daratumumab, with Halozyme Therapeutics’ recombinant or man-made hyaluronidase PH20 enzyme. That enzyme is the core of the company’s proprietary ENHANZE drug-delivery technology. Hyaluronidase destroys components making up the connective tissue locally, enhancing the absorption of drugs and fluids injected under the skin. 

The EC’s decision to approve this new delivery method for Darzalex came soon after the Committee for Medicinal Products for Human Use (CHMP), a branch of the European Medicines Agency (EMA), recommended its approval in April 2020.

“We are delighted that the subcutaneous formulation of Darzalex has been granted marketing authorization in the EU with a broad label so soon after the CHMP positive opinion,” Helen Torley, president and CEO of Halozyme, said in another press release.

“Darzalex SC has the potential to improve the treatment experience for multiple myeloma patients and physicians in the European Union as patients may benefit from a shorter treatment time when compared with a multi-hour intravenous infusion,” Torley said.

The approval was supported by data from two ongoing clinical trials: the COLUMBA Phase 3 trial (NCT03277105), and the PLEIADES Phase 2 trial (NCT03412565).

COLUMBA is comparing the safety and efficacy of into-the-vein and under-the-skin Darzalex. The trial enrolled 522 adults with relapsed or refractory multiple myeloma who received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or failed to respond to both types of therapy.

The study findings showed that, at a median follow-up of 7.5 months, the percentage of participants responding to treatment was similar in those receiving intravenous (37%) and subcutaneous (41%) Darzalex.

Likewise, the time patients lived without showing signs of disease progression was identical in both formulations, at 6.1 months for intravenous Darzalex and 5.6 months for subcutaneous Darzalex.

Although both formulations had similar rates of serious or life-threatening adverse events, fewer patients receiving the subcutaneous formulation experienced infusion-related reactions (13%) compared with those receiving intravenous Darzalex (35%).

The median duration for administering treatment was much shorter in the individuals receiving the medication subcutaneously as compared with those receiving Darzalex intravenously. Specifically, the under-the-skin administration took approximately five minutes, as compared with more than three hours for the into-the-vein delivery.

“Today’s approval marks important progress for the oncology community as it means daratumumab can now be administered in significantly less time, thereby reducing the time patients need to be in the clinical setting,” said Maria-Victoria Mateos, MD, PhD, director of the myeloma unit at the University Hospital of Salamanca-IBSAL in Spain, and the primary investigator of COLUMBA.

In addition to COLUMBA, the approval was supported by PLEIADES, which is evaluating the safety and efficacy of subcutaneous Darzalex in combination with other medications. These include combinations with Velcade (bortezomib), melphalan, and prednisone for newly diagnosed patients, and Revlimid (lenalidomide) along with dexamethasone for those with relapsed or refractory disease.

The findings from PLEIADES showed that nearly all patients (approximately 90%) responded to both combination therapies, which were also found to be safe and well-tolerated.

In the U.S., the fixed-dose subcutaneous formulation of Darzalex, locally known as Darzalex Faspro, was recently approved for four of the six indications for which intravenous Darzalex is currently approved. More information about the specific indications for which Darzalex Faspro has been approved in the U.S. can be found here.