close

Products

Date: 2018-08-31

Type of information: Granting of a Market Authorisation in the EU

Product name: Darzalex® in combination with bortezomib, melphalan and prednisone

Compound: daratumumab in combination with bortezomib, melphalan and prednisone

Therapeutic area: Cancer - Oncology

Action mechanism:

  • monoclonal antibody. Daratumumab is a human CD38 monoclonal antibody with broad-spectrum killing activity. Daratumumab is in clinical development for multiple myeloma. It targets the CD38 molecule which is highly expressed on the surface of multiple myeloma cells and may also have potential in other cancers on which CD38 is expressed, including diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, plasma cell leukemia, acute myeloid leukemia, follicular lymphoma and mantle cell lymphoma. In May, 2013, Daratumumab has been granted Breakthrough Therapy Designation from the FDA for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD.
  • In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab. With the exception of one study sponsored globally by the French multiple myeloma cooperative group, Intergroupe Francophone du Myelome (IFM), Janssen is the global sponsor of all current and future clinical studies for daratumumab.

Company: Janssen Biotech, a J&J company (USA - NJ)

Disease:

  • adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant

Latest news:

  • • On August 31, 2018, Genmab announced that the European Commission (EC) has granted marketing authorization for Darzalex® (daratumumab) in combination with bortezomib, melphalan and prednisone (VMP), for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT).
  • Genmab will receive a milestone payment of $ 13 million from Janssen in connection with the first commercial sales of Darzalex® under the expanded label. The sales are expected to occur quickly after the approval. This milestone payment was included in the financial guidance issued by Genmab originally on February 21, 2018 and then reiterated in subsequent quarterly financial reports, most recently on August 8, 2018, and as such there is no change to the company’s financial guidance following this approval.
  • The positive opinion of the CHMP was based on data from the Phase III ALCYONE (MMY3007) study that showed a reduction of the risk of disease progression or death by 50 percent (Hazard Ratio [HR] = 0.50; 95 percent CI [0.38-0.65], p<0.0001) in patients with newly diagnosed multiple myeloma ineligible for ASCT when daratumumab is combined with VMP. The safety of Darzalex® combination therapy was consistent with the known safety profiles of Darzalex® monotherapy and of therapy with bortezomib, melphalan and prednisone, respectively. This data was presented as a Late-Breaking Abstract at the 2017 American Society of Hematology (ASH) Annual Meeting and simultaneously published in The New England Journal of Medicine in December, 2017.
  • • On 26 July 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for Darzalex®. The committee adopted an extension to the existing indication as follows:
  • - Darzalex® is indicated 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 full indications for Darzalex® will be as follows:
  • • 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.
  • • as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.
  • • 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.
  • • On May 8, 2018, the FDA has approved the use of Darzalex® (daratumumab) in combination with bortezomib, melphalan and prednisone (VMP) for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). The supplemental Biologics License Application (sBLA) for this indication was submitted by Genmab’s licensing partner, Janssen Biotech, Inc., in November 2017. The FDA subsequently granted priority review to the sBLA, with a Prescription Drug User Fee Act (PDUFA) target date of May 21, 2018. “With this label expansion, Darzalex becomes the first antibody therapeutic to be approved for patients with newly diagnosed multiple myeloma,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
  • The approval was based on data from the Phase III ALCYONE study that showed a reduction of the risk of disease progression or death by 50 percent (Hazard Ratio [HR] = 0.50; 95 percent CI [0.38-0.65], p<0.0001) in patients with newly diagnosed multiple myeloma ineligible for ASCT when daratumumab is combined with VMP. The safety of Darzalex combination therapy was consistent with the known safety profiles of Darzalex monotherapy and of therapy with bortezomib, melphalan and prednisone, respectively. This data was presented as a Late-Breaking Abstract at the 2017 American Society of Hematology (ASH) Annual Meeting and simultaneously published in The New England Journal of Medicine in December, 2017. The ALCYONE study (NCT02195479) is a randomized, open-label, multicenter study that included 706 newly diagnosed patients with multiple myeloma who are ineligible for ASCT. Patients were randomized to receive 9 cycles of either VMP [bortezomib (a proteasome inhibitor), melphalan (an alkylating chemotherapeutic agent) and prednisone (a corticosteroid)] combined with daratumumab, or VMP alone. In the daratumumab treatment arm, patients received 16 mg/kg of daratumumab once weekly for six weeks (cycle 1; 1 cycle = 42 days), once every three weeks from cycles 2 to 9, and once every 4 weeks from cycle 9 until disease progression. The primary endpoint of the study is progression free survival (PFS).

Patents:

Submission of marketing authorization application USA :

Submission of marketing authorization application UE:

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2018-05-08

UE authorization: 2018-08-31

Favourable opinion UE: 2018-07-26

Favourable opinion USA:

Orphan status USA:

Orphan status UE:

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes