22 November 2017 - - US-based healthcare company Johnson and Johnson's (NYSE: JNJ) Janssen-Cilag International NV business has submitted a Type II variation application to the European Medicines Agency, for the immunotherapy Darzalex (daratumumab), the company said.

Janssen-Cilag said the application seeks to broaden the existing marketing authorisation to include daratumumab in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.

The regulatory submission is now pending validation by the EMA and is supported by data from the Phase 3 ALCYONE (MMY3007) study.

Additional information about this study can be found at www.ClinicalTrials.gov (NCT02195479), and study findings will be presented at the 59th annual meeting of the American Society of Hematology.

Daratumumab is currently indicated for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent, and who have demonstrated disease progression on the last therapy.

It is a first-in-class biologic targeting CD38, a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage.

Daratumumab is believed to induce tumour cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity and antibody-dependent cellular phagocytosis, as well as through apoptosis, in which a series of molecular steps in a cell lead to its death.

A subset of myeloid derived suppressor cells (MDSCs), CD38+ regulatory T cells (Tregs) and CD38+ B cells (Bregs) were decreased by daratumumab.

Daratumumab is being evaluated in a comprehensive clinical development programme that includes nine Phase 3 studies across a range of treatment settings in multiple myeloma, such as in frontline and relapsed settings.

Additional studies are ongoing or planned to assess its potential for a solid tumour indication and in other malignant and pre-malignant diseases in which CD38 is expressed, such as smouldering myeloma.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialise daratumumab.

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterised by an excessive proliferation of plasma cells.

MM is the second most common form of blood cancer, with around 39,000 new cases worldwide in 2012. MM most commonly affects people over the age of 65 and is more common in men than in women.

The most recent five-year survival data for 2000-2007 show that across Europe, up to half of newly diagnosed patients do not reach five-year survival. Almost 29% of patients with MM will die within one year of diagnosis.

Although treatment may result in remission, unfortunately, patients will most likely relapse as there is currently no cure. While some patients with MM have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.

Patients who relapse after treatment with standard therapies, including PIs and immunomodulatory agents, have poor prognoses and few treatment options available.