Janssen files submission for subcutaneous Darzalex in Europe

Janssen Pharmaceutical has submitted an application to the European Medicines Agency (EMA) seeking approval for subcutaneous formulation of Darzalex (daratumumab) to treat multiple myeloma.

Currently approved for intravenous administration, daratumumab is a human IgG1k monoclonal antibody (mAb) that targets the CD38 protein. The protein is highly expressed on multiple myeloma cells.

The drug stimulates a patient’s immune system against cancer cells. Janssen licensed daratumumab from Genmab in August 2012.

Subcutaneous daratumumab has been formulated using Halozyme’s ENHANZE drug delivery technology, which controls recombinant human hyaluronidase PH20 (rHuPH20) enzyme. 

Janssen’s application for the new formulation is based on positive results from the Phase II PLEIADES and the Phase III COLUMBA clinical trials. 

Janssen-Cilag Europe, Middle East and Africa haematology therapy area lead Dr Patrick Laroche said: "Importantly, subcutaneous daratumumab demonstrated comparable efficacy with the existing IV formulation, reduced the rate of infusion-related reactions and significantly shortened the time it takes for patients to receive treatment, from several hours to approximately five minutes."

PLEIADES is a non-randomised, open-label, parallel assignment trial that assessed 1,800mg subcutaneous formulation of the drug in 240 adults with newly diagnosed or relapsed or refractory multiple myeloma.

Patients were given the drug in combination with bortezomib, lenalidomide and dexamethasone (D-VRd), bortezomib, melphalan, prednisone and dexamethasone (D-VMPd) or lenalidomide and dexamethasone (D-Rd).

The primary aim for the D-VMPd and D-Rd cohorts is overall response rate, while that for the D-VRd cohort is a good partial response or better rate.

The trial was later expanded to include relapsed and refractory multiple myeloma patients who were treated with daratumumab plus carfilzomib and dexamethasone.

In the randomised, open-label, multi-centre COLUMBA trial, the company enrolled 522 patients who had received at least three previous lines of therapy.

This study compared subcutaneous daratumumab to the intravenous formulation. Its co-primary endpoints were objective response rate (ORR) and pre-dose C3D1 daratumumab Ctrough.

Earlier this month, Janssen submitted an application for the subcutaneous formulation to the US Food and Drug Administration (FDA).

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