Approval of Injection Darzalex Combo for Advanced Myeloma Sought in US, EU

Janssen is seeking to extend approval of its under-the-skin formulation of Darzalex (daratumumab) to include its use in combination with Pomalyst (pomalidomide) and dexamethasone to treat relapsed or refractory multiple myeloma patients who received at least one prior line of therapy.

The company submitted applications for this combination therapy to regulatory agencies in the U.S. and the European Union. Darzalex as a subcutaneous injection treatment is available as Darzalex Faspro in the U.S., and as Darzalex SC across the EU.

Janssen’s filings are supported by data from the ongoing APOLLO Phase 3 trial (NCT03180736), where the combination significantly extended the time patients lived without disease worsening and improved complete response rates, compared with Pomalyst and dexamethasone alone.

“Despite strong progress in multiple myeloma over the last decade, it remains a disease with significant unmet need,” Catherine Taylor, MD, a vice president in Medical Affairs Therapeutic Area Strategy with Johnson & Johnson, which owns Janssen, said in a press release.

“We are pleased to pursue this important Darzalex-based combination regimen, which was in the first study showing a significant increase in progression-free survival of a subcutaneous anti-CD38 in combination with pomalidomide and dexamethasone in patients with previously treated multiple myeloma,” Taylor 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 licensed to Janssen in 2012.

This medication was originally developed as an intravenous (into-the-vein) infusion treatment. But Janssen developed a formulation that combines the active ingredient, daratumumab, with recombinant human hyaluronidase, which enables the absorption of drugs and fluids injected under the skin.

Compared with intravenous Darzalex, this subcutaneous formulation demands markedly less expertise to do safely, and takes minutes rather than hours. It is seen as a faster and easier alternative to the original.

While subcutaneous Darzalex was recently approved in the European Union and in the U.S. for some of same indications as the intravenous formulation, none of these approvals covered the combination of subcutaneous Darzalex with Pomalyst and dexamethasone. This combination is approved in the U.S., but for the intravenous formulation.

“The IV formulation of Darzalex, which is approved in combination with pomalidomide and dexamethasone, is an important option for patients with multiple myeloma,” said Craig Tendler, MD, vice president, late development and global medical affairs, Oncology, Janssen Research & Development.

“We are excited to pursue the subcutaneous formulation of Darzalex for this indication as we look to reduce administration time from hours to minutes compared with the IV formulation,” Tendler added.

APPOLO is investigating subcutaneous Darzalex plus Pomalyst and dexamethasone in myeloma patients who had received at least one prior line of therapy, including the immunomodulatory agent Revlimid (lenalidomide) and a proteasome inhibitor.

Sponsored by the European Myeloma Network in collaboration with Janssen, it enrolled 304 patients (median age, 67) and randomly assigned them to either the triple combination or to Pomalyst and dexamethasone alone. Patients were treated until their disease progressed or signs of unacceptable toxicity were reported.

The trial’s main goal is to determine the time patients on each treatment live without disease worsening. Secondary measures include response rates, duration of responses, overall survival, safety, and quality of live.

Janssen announced that APOLLO had met its primary objective earlier this year, with the triple combination resulting in longer periods without disease worsening or death than the combination of Pomalyst and dexamethasone.

The company is presenting full trial results in the abstract “Apollo: Phase 3 Randomized Study of Subcutaneous Daratumumab Plus Pomalidomide and Dexamethasone (D-Pd) Versus Pomalidomide and Dexamethasone (Pd) Alone in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM),” to be discussed at the virtual 62th American Society of Hematology (ASH) Annual Meeting, in December.

After a median follow-up of 16.9 months, these results demonstrate that the subcutaneous Darzalex combination reduced the risk of disease progression or death by 37%. Patients given this triple combination lived without their disease progressing for a median of 12.4 months, compared with 6.9 months for those on Pomalyst and dexamethasone.

At the time of the analysis, survival data was immature and not enough to draw a definite conclusion, but pointed towards better overall survival among patients given the triple combo.

In agreement with these results, complete response rates were higher in the triple combo group (24.5% vs. 3.9%), as was the proportion of very good partial responses (51.0% vs. 19.6%). Patients receiving the subcutaneous Darzalex combination also remained on treatment for longer periods — 11.5 months vs. 6.6 months.

Its safety profile was consistent with the known safety of each these three therapies individually. Serious adverse events experienced more often by patients receiving the triple combination included low levels of several blood cell types and pneumonia.

A similar proportion of patients in both groups discontinued treatment due to treatment-related adverse events. The rate of infusion-related reactions with subcutaneous Darzalex was deemed low (6%).

“Collectively, these data show that D-Pd [Darzalex plus Pomalyst and dexamethasone] is an effective and convenient treatment” for people with relapsed-refractory multiple myeloma who have gone through at least one prior therapy line, its researchers reported.