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FDA grants Priority Review for Roche’s Gazyva in previously untreated follicular lymphoma

On august 28, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for Gazyva (obinutuzumab) in combination with chemotherapy followed by Gazyva alone for people with previously untreated follicular lymphoma, one of the most common blood cancers among adults (Press release, Hoffmann-La Roche, AUG 28, 2017, View Source [SID1234520315]). Follicular lymphoma, a slow-growing (indolent) form of non-Hodgkin lymphoma, is incurable and characterized by cycles of remission and relapse.
"Follicular lymphoma becomes harder to treat each time it returns, and the goal of initial treatment is to prevent the cancer from progressing for as long as possible," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Based on the GALLIUM study, Gazyva-based treatment significantly improved progression-free survival over the current standard of care, and we are committed to bringing this potential new option to patients as soon as possible."

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The sBLA is based on results of the GALLIUM study, which is the first Phase III study in previously untreated follicular lymphoma to show superior progression-free survival (PFS) over Rituxan (rituximab)-based treatment, the current standard of care. Adverse events (AEs) with either Gazyva or Rituxan were consistent with those seen in previous studies.

The FDA is expected to make a decision on approval under Priority Review by 23 December, 2017. Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention or diagnosis of a serious disease. Additional submissions of the GALLIUM data to health authorities around the world are ongoing.

About the GALLIUM study
GALLIUM (NCT01332968) is a global Phase III open-label, multicenter, randomized two-arm study examining the efficacy and safety of Gazyva plus chemotherapy followed by Gazyva alone for up to two years, as compared head-to-head against Rituxan plus chemotherapy followed by Rituxan alone for up to two years. Chemotherapies used were CHOP, CVP or bendamustine and were selected by each participating study site prior to beginning enrollment.

GALLIUM included 1401 patients with previously untreated indolent non-Hodgkin lymphoma (iNHL), of which 1202 patients had follicular lymphoma. The primary endpoint of the study was investigator-assessed progression-free survival (PFS) in patients with follicular lymphoma, with secondary endpoints including PFS assessed by independent review committee (IRC) in patients with follicular lymphoma, PFS in the overall study population (iNHL), response rate (overall response, ORR; and complete response, CR), overall survival (OS) and safety. The study is being conducted in cooperation with the GLSG (Germany), the East German Study Group Hematology and Oncology (OSHO; Germany) and the NCRI (United Kingdom). Results after a follow-up period of 41.1 months showed:
Gazyva-based treatment reduced the risk of disease worsening or death (PFS, as assessed by investigator) by 32 percent compared to Rituxan-based treatment (HR=0.68; 95 percent CI 0.54-0.87; p=0.0016).

IRC-assessed PFS was consistent with investigator-assessed PFS. As assessed by IRC, Gazyva-based treatment reduced the risk of disease worsening or death by 28 percent compared to Rituxan-based treatment (HR=0.72; 95 percent CI 0.56-0.93; p=0.0018). Median PFS has not yet been reached in either treatment arm.

The most common Grade 3-5 AEs that occurred more often in the Gazyva arm compared to the Rituxan arm were low white blood cell count (neutropenia, 46.7 percent vs. 39.5 percent), infections (20.3 percent vs. 16.4 percent), infusion-related reactions (IRRs, 12.4 percent vs. 6.7 percent), low platelet count (thrombocytopenia, 6.1 percent vs. 2.7 percent), new tumors (second malignancies, 4.7 percent vs. 2.7 percent) and cardiac events (3.9 percent vs. 2.8 percent).

GALLIUM is the third positive Phase III study for Gazyva, following the CLL11 study in patients with previously untreated chronic lymphocytic leukaemia (CLL) and the GADOLIN study in patients with indolent (slow-growing) non-Hodgkin lymphoma whose disease progressed during or within six months of prior Rituxan-based therapy.

About Gazyva (obinutuzumab)
Gazyva is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells. Gazyva is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system.

Gazyva is marketed as Gazyvaro in the EU and Switzerland. Gazyva/Gazyvaro is currently approved in more than 80 countries in combination with chlorambucil, for people with previously untreated chronic lymphocytic leukaemia (CLL), and in combination with bendamustine for people with certain types of previously treated follicular lymphoma. The approvals in CLL were based on the CLL11 study, showing significant improvements with Gazyva/Gazyvaro plus chlorambucil across multiple clinical endpoints, including PFS, overall response rate (ORR), complete response rate (CR), and minimal residual disease (MRD) when compared head-to-head with MabThera/Rituxan plus chlorambucil.

The approvals in certain types of previously treated follicular lymphoma were based on the phase III GADOLIN study, in people with follicular lymphoma who did not respond to or who progressed during or within six months of prior MabThera/Rituxan-based therapy, showing a significant improvement in PFS and overall survival (OS) with Gazyva/Gazyvaro-based therapy compared to bendamustine alone.

Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

About Follicular Lymphoma
Follicular lymphoma is the most common indolent (slow-growing) form of non-Hodgkin lymphoma (NHL), accounting for about one in five cases of NHL1. It is considered incurable and relapse is common. Every day, more than 50 people in Europe are diagnosed with this type of NHL2. It is estimated that more than 75,000 people are diagnosed with follicular lymphoma each year worldwide2.
About Roche in haematology

Faslodex receives US FDA approval as monotherapy for expanded use in breast cancer

On August 28, 2017 AstraZeneca reported that the US Food and Drug Administration (FDA) has approved Faslodex (fulvestrant) 500mg as monotherapy for expanded use in women with hormone-receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer, who have gone through menopause and have not received previous endocrine therapy (Press release, AstraZeneca, AUG 28, 2017, View Source [SID1234520314]).

The FDA approval is based on data from the Phase III FALCON trial, which were published in the November 2016 issue of The Lancet.

Jamie Freedman, Executive Vice President, Head of the Oncology Business Unit, AstraZeneca said: "We’re pleased that the landmark FALCON trial results demonstrated the efficacy of Faslodex as initial monotherapy treatment for women who are living with HR+ HER2- advanced breast cancer. This approval, building on more than 15 years of clinical experience, means more patients can have the opportunity to receive Faslodex earlier in the treatment journey."

Matthew Ellis, MD, PhD, Director of the Lester and Sue Smith Breast Center, part of the NCI-designated Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, said: "This study provides evidence that using fulvestrant as the first option for previously untreated hormone receptor-positive advanced breast cancer will prolong the time before the disease advances and alternative therapies are required."

The FALCON trial was designed to demonstrate superiority and included 462 postmenopausal women with HR+ metastatic or locally-advanced breast cancer. The results showed a statistically-significant increase in investigator-assessed median progression-free survival (PFS), representing a 20% reduction in the risk of disease progression or death – median PFS of 16.6 months in patients who received Faslodex, compared to 13.8 months in patients receiving the aromatase inhibitor anastrozole 1mg (HR: 0.797; 95% CI: 0.637-0.999; p=0.049).

Faslodex is a hormonal therapy that targets the oestrogen receptor (ER), which can influence the growth of HR+ metastatic breast cancer (MBC), and helps to slow cancer growth by blocking the ER and targeting it for degradation. The most common adverse reactions (≥10%) of any grade reported in patients in the Faslodex arm were arthralgia, hot flash, fatigue, and nausea.

About FALCON

The FALCON (Fulvestrant and AnastrozoLe COmpared in hormonal therapy-Naïve advanced breast cancer) trial is a Phase III, randomised, double-blind, multicentre trial comparing the antitumour effects and tolerability profile of a 500mg dose of Faslodexplus placebo with a 1mg dose of anastrozole plus placebo, in postmenopausal women with HR+, locally-advanced or metastatic breast cancer who have not been treated previously with any hormonal medicine.

The FALCON trial was designed on the basis of positive results from the Phase II FIRST trial, which demonstrated a median overall survival nearly six months longer with Faslodex compared to anastrozole.

About Advanced Breast Cancer

Advanced/metastatic breast cancer refers to Stage III and IV breast cancer. Stage III disease may also be referred to as locally-advanced breast cancer, while metastatic disease is the most-advanced stage of breast cancer (Stage IV), and occurs when cancer cells have spread beyond the initial tumour site to other organs of the body outside the breast. Since there is no cure for the disease, the goal of current treatment is to delay disease worsening or death.

About Faslodex

First approved in 2002, Faslodex was used as a monotherapy for the treatment of postmenopausal women with HR+ MBC whose cancer had progressed following prior anti-oestrogen therapy. In 2016, FDA approved Faslodex in combination with palbociclib for the treatment of women with HR+, HER2- advanced or MBC, whose cancer has progressed after endocrine therapy.

On 26 July 2017, the European Commission (EC) approved Faslodex for the treatment of oestrogen-receptor positive, locally-advanced breast cancer in postmenopausal women not previously treated with endocrine therapy.

Novartis announces analysis published in The Lancet showing ACZ885 reduced lung cancer mortality by 77% in the CANTOS study with further studies planned

On August 27, 2017 Novartis reported primary data from the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), a Phase III study evaluating the role of ACZ885, an interleukin-1ß antibody, in people with a prior heart attack and inflammatory atherosclerosis as measured by high-sensitivity C-reactive protein (hsCRP), a known marker of inflammation, at levels of >=2mg/L (Press release, Novartis, AUG 27, 2017, View Source [SID1234520317]). An additional pre-planned analysis showed that ACZ885 reduced the rate of lung cancer incidence and mortality among study participants. Effects were dose-dependent with a relative risk reduction of 67% finding for lung cancer (HR 0.33 [95% CI: 0.18-0.59]) and 77% for lung cancer mortality (HR 0.23 [95% CI: 0.10-0.54]) observed among patients receiving the 300mg dose of ACZ885 every three months[1]. As part of the study design, all cases of cancers were reviewed by an independent panel of oncologists unaware of study drug allocation. Details of the lung cancer analysis were presented today, alongside the cardiovascular outcomes data, at the European Society of Cardiology (ESC) Congress and published simultaneously in The Lancet[1],[2]. The details of the cardiovascular findings were also presented at ESC and simultaneously published in The New England Journal of Medicine[3].

"The results of CANTOS are exciting because we now have clear evidence that in addition to lowering cholesterol, targeting inflammation reduces patients’ risk of cardiovascular disease, and perhaps even lung cancer," said Paul Ridker, MD, CANTOS Study Chairman and
Director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital. "From a cardiologist perspective, these findings represent a novel approach to the treatment of heart disease with the potential to also help patients with certain cancers."

"By targeting the IL-1ß pathway, CANTOS study findings provide further insights into the role of inflammation in lung cancer and medical researchers additional data to conduct trials to prove this important hypothesis," said Howard A. "Skip" Burris, MD, President of Clinical Operations and Chief Medical Officer, Sarah Cannon Research Institute (Nashville, TN) and Chair of the CANTOS Cancer Adjudication Committee.

"These data are a significant milestone because they show that selectively targeting inflammation with ACZ885 reduces cardiovascular risk and that ACZ885 may also be an important immuno-oncology therapy targeting IL-1ß for lung cancer," said Vas Narasimhan, Global Head, Drug Development and Chief Medical Officer, Novartis. "We look forward to submitting the CANTOS cardiovascular data to regulatory authorities for approval and initiating additional phase III studies in lung cancer."

IL-1ß is a key cytokine in the inflammatory pathway known to drive the continued progression of inflammatory atherosclerosis. By inhibiting the tumor micro-environment mediated by interleukin-1ß, the CANTOS study data analysis explored whether ACZ885, a monoclonal antibody that targets and inhibits the action of IL-1ß, could have an impact on the occurrence and progression of cancer.

With more than 10,000 patients enrolled in the study over the last six years, CANTOS was one of the largest and longest-running clinical trials in Novartis’ history. Trial participants with a prior history of atherosclerosis, a hsCRP level of >=2mg/L, and who were free of previously-diagnosed cancer, received either placebo or one of three doses of ACZ885 (50mg, 150mg, and 300mg subcutaneously every 3 months). All participants received current standard of care therapies, with 91% of participants taking lipid-lowering statins. During a median follow up of 3.7 years, as compared to placebo, ACZ885 resulted in dose dependent reduction in hsCRP of 26 to 41% and a dose-dependent reduction in IL-6 of 25 to 43% (p=<0.0001). For all cancer related mortality (n=196 across treatment), ACZ885 resulted in a significant reduction compared to placebo at the 300mg dose (HR 0.49: [95% CI: 0.31-0.75] p=0.0009). Incident lung cancer (n=129 across treatment) was reduced at the 300mg dose versus placebo (HR 0.33 [95% CI: 0.18-0.59]; p=<0.0001) and the 150mg dose versus placebo (HR 0.61 [95% CI: 0.39-0.97]; p=0.034). Lung cancer mortality was significantly less common at the 300mg dose versus placebo (HR 0.23 [95% CI: 0.10-0.54] p=0.0002)[1].

The overall rates of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar to placebo across all ACZ885 doses. In the six year-long study, serious infections were reported in 11.7% vs 10.2% and malignancies were reported in 6.7% vs 7.1% of participants (ACZ885 300mg vs placebo, respectively). Fatal infections occurred in about one per 1,000 patients in placebo. Although rare, this occurrence was higher in the combined ACZ885 group than placebo. On the other hand, cancer deaths were cut in half by ACZ885 such that there was a non-significant reduction in death from any cause[1].

Over the last decade, the development of immuno-oncology agents have become a primary therapeutic category in fighting certain types of cancers and have improved the outcome for patients, especially those living with lung cancer. Novartis is exploring a number of immunotherapy approaches including priming or educating the immune system so that it can recognize cancer as a threat, attempting to unleash immune cells that have already been primed, and investigating ways to make the tumor more accessible to immune cells. This scientific research is helping the medical community to understand how cancer is responding to therapy – including which patients may benefit from treatments.

About CANTOS (NCT01327846)
The Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) (NCT01327846) is a randomized, double-blind, placebo-controlled, event-driven Phase III study designed to evaluate the efficacy, safety and tolerability of quarterly subcutaneous injections of ACZ885 (also known as canakinumab) in combination with standard of care in the prevention of recurrent cardiovascular (CV) events among 10,061 people with a prior myocardial infarction (MI) and with a high-sensitivity C-reactive protein (hsCRP) level of >=2mg/L. The study evaluated three different doses of ACZ885 vs placebo. The primary endpoint of the study was time to first occurrence of major adverse CV event (MACE), a composite of CV death, non-fatal MI, and non-fatal stroke. Secondary endpoints included time to first occurrence of the composite CV endpoint consisting of CV death, non-fatal MI, non-fatal stroke and hospitalization for unstable angina requiring unplanned revascularization; time to new onset type 2 diabetes among people with pre-diabetes at randomization; time to occurrence of non-fatal MI, non-fatal stroke or all-cause mortality; and time to all-cause mortality. The median follow-up time was 3.7 years. The study ran for approximately six years.
In agreement with the US Food and Drug Administration in 2010, incident cancers were adjudicated by a blinded independent oncology monitoring committee. Data on incident cancers, including cancer deaths, were collected as serious adverse events and analyzed in a prospective fashion. History of cancer was an exclusion criteria to study enrollment (baseline CT scans were not conducted) and diagnosis of cancer led to a discontinuation of treatment with ACZ885 as per protocol.

About ACZ885 (canakinumab)
ACZ885 (canakinumab) is a selective, high-affinity, fully human monoclonal antibody that inhibits IL-1ß, a key cytokine in the inflammatory pathway known to drive the continued progression of inflammatory atherosclerosis. ACZ885 works by blocking the action of IL-1ß for a sustained period of time, therefore inhibiting inflammation that is caused by its over-production. ACZ885 is the first and only investigational treatment which has shown that selectively targeting inflammation significantly reduces cardiovascular risk.

TESARO Announces Nine Data Presentations at the 2017 European Society for Medical Oncology (ESMO) Annual Meeting

On August 25, 2017 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that data from nine abstracts will be presented at the 2017 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) annual meeting, September 8 to September 12, 2017, in Madrid (Press release, TESARO, AUG 25, 2017, View Source [SID1234520316]).

"We are excited that a wealth of data from the landmark ENGOT-OV16/NOVA trial will be presented at this year’s ESMO (Free ESMO Whitepaper) Annual Meeting," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "Patient-reported quality of life data for patients treated with niraparib versus placebo will be featured in an oral presentation and the results of two post-hoc analyses, the observed exposure-response relationship of niraparib in gBRCAmut and non-gBRCAmut patients, and the safety and efficacy of niraparib in elderly patients, will be subjects for poster discussions. In addition, data from the Phase 1/2 trial of niraparib plus pembrolizumab in patients with triple-negative breast cancer or recurrent platinum-resistant ovarian cancer (TOPACIO) will be highlighted in a poster discussion. Finally, a poster will be presented detailing results from the Phase 1 study of TSR-042, our anti-PD-1 antibody."

Please plan to visit TESARO at Booth #53 for information about VARUBY and our pipeline.

Presentation Details (all times local):

ZEJULA (niraparib)

Friday, September 8, 2017, 4:00 PM to 5:30 PM
Quality of life in recurrent ovarian cancer patients treated with niraparib: Results from the ENGOT-OV16/NOVA TRIAL
Proffered Paper Session, Abstract: 930O, Location: Cordoba Auditorium

Saturday, September 9, 2017, 9:15 AM to 10:45 AM
Safety and efficacy of niraparib in elderly patients (Pts) with recurrent ovarian cancer (OC)
Poster Discussion Session, Abstract: 934PD, Location: Cartagena Auditorium

Saturday, September 9, 2017, 9:15 AM to 10:45 AM
The exposure-response relationship of niraparib in patients (pts) with gBRCAmut and non-gBRCAmut: results from the Phase 3 ENGOT-OV16/NOVA Trial
Poster Discussion Session, Abstract:933PD, Location: Cartagena Auditorium

Saturday, September 9, 2017, 1:15 PM to 2:15 PM
Modeling and impact of organ function on the population pharmacokinetics (PK) of niraparib, a selective poly (ADP-ribose) polymerase (PARP)—1 and —2 inhibitor
Poster Display Session, Abstract: 964P, Location: Hall 8

Saturday, September 9, 2017, 1:15 PM to 2:15 PM
A randomized, double-blind, placebo-controlled multicenter phase 3 trial of niraparib maintenance treatment in patients with advanced ovarian cancer following frontline chemotherapy (PRIMA)
Poster Display Session, Abstract: 986TiP, Location: Hall 8

Saturday, September 9, 2017, 1:15 PM to 2:15 PM
A phase 1 study to evaluate the safety and tolerability of bevacizumab-niraparib combination therapy and determine the recommended phase 2 dose (RP2D) in women with platinum-sensitive epithelial ovarian cancer (ENGOT-OV24/AVANOVA1)
Poster Display Session, Abstract: 953P, Location: Hall 8

Saturday, September 9, 2017, 1:15 PM to 2:15 PM
Disease burden during the "watchful waiting" period in patients with recurrent ovarian cancer
Poster Display Session, Abstract: 962P, Location: Hall 8

Monday, September 11, 2017, 9:15 AM to 10:45 AM
Dose-finding combination study of niraparib and pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC) or recurrent platinum-resistant epithelial ovarian cancer (OC) (TOPACIO/Keynote-162)
Poster Discussion Session, Abstract: 1143PD, Location: Bilbao Auditorium

Niraparib is marketed in the United States under trade name ZEJULA. Niraparib has not been approved by any regulatory agencies outside of the United States.

The TOPACIO trial is being conducted in collaboration with Merck Sharp & Dohme B.V., a subsidiary of Merck & Co., Inc., which is providing support for the trial.

TSR-042 (anti-PD-1 antibody)

Sunday, September 10, 2017, 1:15 PM to 2:15 PM
Safety, pharmacodynamic, and pharmacokinetic profile of TSR-042, an anti—PD—1 monoclonal antibody, in patients with advanced solid tumors
Poster Display Session, Abstract: 1185P, Location: Hall 8

About ZEJULA (Niraparib)
Niraparib is marketed in the United States under trade name ZEJULA. ZEJULA (niraparib) is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. In preclinical studies, ZEJULA concentrates in the tumor relative to plasma, delivering greater than 90% durable inhibition of PARP 1/2 and a persistent antitumor effect. Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including some fatal cases, was reported in patients treated with ZEJULA. Discontinue ZEJULA if MDS/AML is confirmed. Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia), as well as cardiovascular effects (hypertension and hypertensive crisis) have been reported in patients treated with ZEJULA. Monitor complete blood counts to detect hematologic adverse reactions, as well as to detect cardiovascular disorders, during treatment. ZEJULA can cause fetal harm and females of reproductive potential should use effective contraception. Please see full prescribing information, including additional important safety information, available at www.zejula.com.

About TSR-042

TSR-042 is a monoclonal antibody targeting PD-1 and was developed as part of the collaboration between TESARO and AnaptysBio, Inc. This collaboration was initiated in March of 2014, and is focused on the development of monospecific antibody drugs targeting PD-1, TIM-3 (TSR-022), and LAG-3 (TSR-033), in addition to a bi-specific antibody drug candidate targeting PD-1/LAG-3.

Genmab Announces Positive Topline Results in Phase III ALCYONE Study of Daratumumab in Front Line Multiple Myeloma

On August 24, 2017 Genmab A/S (Nasdaq Copenhagen: GEN) reported topline results from the Phase III ALCYONE study (MMY3007) of daratumumab in combination with bortezomib, melphalan and prednisone (VMP) versus VMP alone as front line treatment for newly diagnosed patients who are not considered candidates for autologous stem cell transplantation (ASCT) (Press release, Genmab, AUG 24, 2017, View Source [SID1234520312]). The study met the primary endpoint of improving progression free survival (PFS) at a pre-planned interim analysis (Hazard Ratio (HR) = 0.50 (95% CI 0.38-0.65), p < 0.0001).

Treatment with daratumumab reduced the risk of disease progression or death by 50%, as compared to those who did not receive daratumumab. The median PFS for patients treated with daratumumab in combination with VMP has not been reached, compared to an estimated median PFS of 18.1 months for patients who received VMP alone.
Overall, the safety profile of daratumumab in combination with VMP is consistent with the known safety profile of the VMP regimen and the known safety profile of daratumumab.

Based on the results at the pre-planned interim analysis conducted by an Independent Data Monitoring Committee (IDMC), it was recommended that the data be unblinded. All patients will continue to be monitored for safety and overall survival. Further analysis of the safety and efficacy data is underway and Janssen Biotech, Inc., which licensed daratumumab from Genmab in 2012, will discuss with health authorities the potential for a regulatory submission for this indication. The data are expected to be submitted for presentation at an upcoming medical conference and for publication in a peer-reviewed journal.

"The interim results of the ALCYONE study yet again illustrate the potential of daratumumab in multiple myeloma in combination with existing treatment regimens; this time with VMP in the front line setting. We are very pleased with the outcome of the pre-planned interim analysis in this study, which adds further to our hope that daratumumab could potentially become the critical driver redefining combination treatment in multiple myeloma," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

Today’s news does not impact Genmab’s 2017 financial guidance.

About the study
This Phase III study (NCT02195479) is a randomized, open-label, multicenter study and includes 706 newly diagnosed patients with multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT). Patients were randomized to receive 9 cycles of either daratumumab combined with VMP [bortezomib (a proteasome inhibitor), melphalan (an alkylating chemotherapeutic agent) and prednisone (a corticosteroid)], 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), followed by once every three weeks (cycles 2-9). Following the 9 cycles, patients in the daratumumab treatment arm continued to receive 16 mg/kg of daratumumab once every four weeks until disease progression. The primary endpoint of the study is progression free survival (PFS).

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 30,330 new patients were expected to be diagnosed with multiple myeloma and approximately 12,650 people were expected to die from the disease in the U.S. in 2016.3 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5 Patients who relapse after treatment with standard therapies, including proteasome inhibitors or immunomodulatory agents, have poor prognoses and few treatment options.6

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.7 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe 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. DARZALEX is the first human CD38 monoclonal antibody approved in Europe. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death). 7,8,9,10,11

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline multiple myeloma settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, NKT-cell lymphoma, amyloidosis, myelodysplastic syndromes and solid tumors. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.