Janssen files promising myeloma contender in Europe

Janssen-Cilag has submitted its new myeloma treatment, daratumumab, for regulatory review in Europe.

The drug has been filed for use in patients with relapsed and refractory multiple myeloma, and has shown impressive results in these heavily pre-treated patients.

Patients with the incurable blood cancer who become refractory to both proteasome inhibitors (PI) such as Janssen’s own Velcade or immunomodulatory (IMiD) agents such as Celgene’s Revlimid have a poor prognosis.

These patients have an estimated median overall survival of nine months, and currently have few options for further treatment.

Daratumumab works by binding to CD38, a signalling molecule found on the surface of multiple myeloma cells. In doing so, the drug triggers the patient’s own immune system to attack the cancer cells, resulting in rapid tumour cell death through multiple immune-mediated, and other, mechanisms of action.

The filing is based on data from the phase II MMY2002 (SIRIUS) monotherapy study, which was presented at the ASCO cancer congress in May, plus data from the phase 1I/II GEN501 monotherapy study, recently published in the NEJM.

The primary efficacy endpoint was overall response rate (ORR). Ninety-five percent of patients in the study were double refractory to a PI and IMiD. Patients received three or more lines of prior therapy (median of five), including a PI and an IMiD. Daratumumab achieved an ORR of 29 per cent in the group of patients who received 16 mg/kg (n=106) as a single-agent therapy, with a well-tolerated safety profile.

The ORR outcomes of MMY2002 are similar to the ORR data in the phase I/II GEN501 study, in which safety was the primary endpoint.

Five phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases in which CD38 is expressed, such as smouldering myeloma and non-Hodgkin lymphoma.

The myeloma market has become increasingly crowded in the last few years, but Janssen’s drug looks promising against other new players. Amgen’s Kyprolis is already approved in refractory patients, with a 23 per cent ORR and median duration of 7.8 months.

Janssen’s drug was one of the first to gain the FDA’s breakthrough therapy designation in 2013, and has just been accepted by the US regulator for priority review.

Janssen acquired rights to the drug via a $1.1 billion deal with Genmab, and analysts believe it should recoup this cost with blockbuster peak sales.

The firm is now pursuing late-stage combination studies for use as a front-line treatment, which will be vital to maximise revenues.

Meanwhile Bristol-Myers Squibb also has a contender in late-stage development, elotuzumab, which has shown good performance when combined with Revlimid and dexamethasone.

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