1stOncology™: Cancer Intelligence Service – Page 17029 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

U.S. FDA Grants Priority Review for Daratumumab for Double Refractory Multiple Myeloma

On September 4, 2015 Genmab A/S (OMX: GEN) reported that the U.S. Food and Drug Administration (FDA) has granted Priority Review to the Biologics License Application (BLA) for daratumumab (Press release, Genmab, SEP 4, 2015, View Source [SID:1234507401]). The BLA is for daratumumab as a treatment for patients with multiple myeloma who have received at least three different lines of therapy including both a proteasome inhibitor and an immunomodulatory agent (IMiD) or who are double refractory to a proteasome inhibitor and an IMiD. A rolling BLA submission was started by Genmab’s licensing partner, Janssen Biotech, Inc. in June and was completed on July 9, 2015. In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

Priority Review is an FDA designation for drugs that treat a serious condition and may provide a significant improvement in safety or efficacy. The FDA aims to complete its review of the daratumumab BLA within six months and has assigned a Prescription Drug User Fee Act (PDUFA) target date of March 9, 2016.

"We are pleased that the FDA has granted Priority Review for daratumumab in double refractory multiple myeloma. If approved, daratumumab has the potential to make a real difference in the lives of people who have run out of other treatment options for multiple myeloma," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The BLA submission includes data from the Phase II study (Sirius MMY2002) of daratumumab in multiple myeloma patients who have received at least three prior lines of therapy including both a PI and an IMiD, or who are double refractory to a PI and an IMiD. However, safety and efficacy data from the Phase I/II study (GEN501) and safety data from three other studies, have also been included in the BLA submission. Daratumumab received a Breakthrough Therapy Designation for this indication from the FDA in May 2013.

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 26,850 new patients will be diagnosed with multiple myeloma and approximately 11,240 people will die from the disease in the U.S. in 2015.3 Globally, it is estimated that 124,225 people will be diagnosed and 87,084 will 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 PIs or IMiDs, have poor prognoses and few treatment options.6

About daratumumab
Daratumumab is an investigational 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. It induces rapid tumor cell death through multiple immune-mediated mechanisms7, including complement-dependent cytotoxicity7, antibody-dependent cellular phagocytosis8 and antibody-dependent cellular cytotoxicity7, as well as via induction of apoptosis9 . 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 on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin lymphoma. Daratumumab has been granted Breakthrough Therapy Designation from the US FDA.

Clovis Oncology Announces Data Presentations at 16th World Conference on Lung Cancer

On September 4, 2015 Clovis Oncology (NASDAQ:CLVS)reported that rociletinib, the company’s oral targeted covalent (irreversible) mutant-selective inhibitor of epidermal growth factor receptor (EGFR) in development for the treatment of EGFR-mutated, T790M positive non-small cell lung cancer (NSCLC), is the subject of four mini-oral presentations and two poster sessions at the 16th World Conference on Lung Cancer (Press release, Clovis Oncology, SEP 4, 2015, View Source;p=RssLanding&cat=news&id=2085448 [SID:1234507399]). Hosted by the International Association for the Study of Lung Cancer (IASLC), the conference will take place September 6-9, 2015 in Denver.

"We look forward to sharing updated data from the pivotal TIGER-X trial, analyzing the clinical activity of rociletinib in multiple subsets of patients with advanced EGFR mutant NSCLC, specifically in those with a history of CNS metastases, as well as in patients with T790M negative disease," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "The coming months are shaping up to be a very busy and important time for rociletinib, as we move forward with our pivotal TIGER clinical trial program and prepare for potential product launches in both the United States and Europe."

Mini-Oral Presentations

Rociletinib in NSCLC patients with negative central testing for T790M in TIGER-X (Abstract #951/MINI03.10)

Heather Wakelee, MD, Stanford University Medical Center
Monday, Sept. 7, 4:45-6:15pm MT
Location: Four Seasons Ballroom F1 + F2
Identification of effective drug combinations to prevent or delay resistance to the EGFR mutant selective inhibitor rociletinib (CO-1686) (Abstract #3010/MINI09.04)

Andrew D. Simmons, PhD, Clovis Oncology
Monday, Sept. 7, 4:45-6:15pm MT
Location: Rooms 205 + 207
Dose optimization of rociletinib for EGFR mutated NSCLC (Abstract #967/MINI16.03)

Jonathan W. Goldman, MD, UCLA Health
Tuesday, Sept. 8, 4:45-6:15pm MT
Location: Four Seasons Ballroom F3 + F4
Activity of rociletinib in EGFR mutant NSCLC patients with a history of CNS involvement (Abstract #965/MINI16.04)

D. Ross Camidge, MD, PhD, University of Colorado Denver
Tuesday, Sept. 8, 4:45-6:15pm MT
Location: Four Seasons Ballroom F3 + F4
Poster Sessions

Poster P1.01-076 – TIGER-1: A randomized, open-label, phase 2/3 study of rociletinib (CO-1686) or erlotinib as first-line treatment for EGFR-mutant non-small cell lung cancer

D. Ross Camidge, MD, PhD, University of Colorado Denver
Monday, Sept. 7, 9:30am-4:45pm MT
Location: Exhibit Hall
Poster P1.01-086 – TIGER-3: A phase 3, open-label, randomized study of rociletinib versus cytotoxic chemotherapy in patients with mutant EGFR non-small cell lung cancer progressing on prior EGFR tyrosine kinase inhibitor therapy and doublet chemotherapy

James Chih-Hsin Yang, National Taiwan University Hospital
Monday, Sept. 7, 9:30am-4:45pm MT
Location: Exhibit Hall
About Rociletinib

Rociletinib is an oral, potent, mutant-selective inhibitor of epidermal growth factor receptor (EGFR) under investigation for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). Rociletinib targets the activating mutations of EGFR (L858R and Del19), while also inhibiting the dominant acquired resistance mutation, T790M, which develops in approximately 60 percent of patients treated with first- and second-generation EGFR inhibitors, while sparing wild-type, or "normal" EGFR at anticipated therapeutic doses. Rociletinib was granted Breakthrough Therapy designation by the U.S. FDA in May 2014.

DelMar Pharmaceuticals Reports Fiscal 2015 Year-End Financial Results and Provides Corporate Update

On September 4, 2015 DelMar Pharmaceuticals, Inc. (OTCQX: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported its financial results for the fiscal year ending June 30, 2015 and provided an overview of recent Company highlights and expected near-term milestones (Press release, DelMar Pharmaceuticals, SEP 4, 2015, View Source [SID:1234507397]).

RECENT HIGHLIGHTS

VAL-083 (dianhydrogalactitol), for the treatment of refractory glioblastoma multiforme (GBM)

Completed Phase I dose-escalation in the clinical trial in refractory GBM and presented data supporting a dose response trend.
Patients receiving a dose >/= 30mg/m2 had a median survival of nine (9) months vs. five (5) months at doses up to 5mg/m2.
Initiated a Phase II expansion cohort for the GBM study at a dose of 40mg/m2. We anticipate enrolling approximately 14 patients in the Phase II expansion cohort.

To date, 19 patients have been screened and six (6) patients have initiated treatment with VAL-083 at the 40mg/m2 dose.
To further explore the therapeutic window, three (3) patients have also initiated treatment at an interim dose of 45mg/m2. The Phase II expansion cohort may be continued at this higher dose if warranted by safety data.

Continued preparation for advancement into registration-directed Phase II/III clinical trials.

Presented additional data on the activity of VAL-083 against temozolomide-resistant GBM and its potential as a therapeutic option for patients who fail or are unlikely to respond to current front-line therapy.

Added the fourth and fifth Phase I/II clinical trial sites at Mayo Clinic Cancer Center in Rochester, MN and Sarah Cannon Cancer Research Center at HealthOne in Denver, CO.

Expanding our drug development pipeline: Lung and Ovarian Cancer

Non-small cell lung cancer (NSCLC)

Presented preclinical data in lung cancer models supporting differentiation of VAL-083 versus platinum-based chemotherapy in treatment of drug-resistant NSCLC.
Announced plans to initiate clinical research in NSCLC in collaboration with Guangxi Wuzhou Pharmaceutical Group (Co) Ltd.
Ovarian Cancer

Announced the upcoming presentation of new non-clinical data supporting the activity of VAL-083 in treatment-resistant ovarian cancer.

Corporate

Raised $2.6 million gross proceeds in a registered direct offering.

Announced an additional non-dilutive funding increase of up to CDN$287,000 from the National Research Council of Canada Industrial Research Assistance Program for continued support of our non-clinical research programs.

Continued to take steps toward listing our common shares on a national stock exchange including reducing the derivative liability component of our balance sheet, appointing new independent directors and establishing required corporate governance structures and policies.

"We have made tremendous progress during this fiscal year in executing our clinical development strategy and driving value into our lead product candidate VAL-083. The promising results of the Phase I dose-escalation study were instrumental in advancing the program in GBM. We anticipate reporting additional data from the Phase II expansion cohort at upcoming peer reviewed scientific meetings and are implementing our plan to advance VAL-083 into a Phase II/III registration-directed clinical program in refractory GBM," stated Jeffrey Bacha, president & CEO of DelMar Pharmaceuticals.

"Based on promising results of grant-funded research, we are also preparing to expand the VAL-083 clinical research portfolio into non-small cell lung cancer (NSCLC), which will be funded through our collaboration with Guangxi Wuzhou Pharmaceutical (Group) Co., Ltd.," added Mr. Bacha. "We believe our VAL-083 program in NSCLC has significant future potential for partnering opportunities."

Mr. Bacha concluded, "We believe that the unique mechanism of action of VAL-083 provides a basis to address unmet medical needs in a range of cancers."

FY2016 MILESTONES

Complete enrollment of the Phase II expansion study in refractory GBM;
Advance VAL-083 into registration-directed Phase II/III clinical trials;
Expand our clinical development activities through new trials supported by our collaboration with Guangxi Wuzhou Pharmaceutical (Group) Co. Ltd.;
Continue to actively communicate our progress to the investment and medical communities through presentations at peer-reviewed scientific meetings;
Continue to build our intellectual property portfolio; and
Implement strategies to enable DelMar to meet qualifications to list its shares on a national stock exchange.

CONFERENCE CALL DETAILS
The DelMar business update conference call and live webcast is scheduled to begin today at 11:00 a.m. Eastern Time / 8:00 a.m. Pacific Time. For both "listen-only" participants and those who wish to take part in the question and answer portion of the call, the telephone Dial-in Number is (866) 394-9399 (toll-free) with Conference ID 22042321. A link to the webcast and slides will be available on the IR Calendar of the Investors section of the Company’s website at www.delmarpharma.com, and will be archived for 30 days.

SUMMARY OF FINANCIAL RESULTS FOR THE FISCAL YEAR ENDED JUNE 30, 2015
For the twelve months ended June 30, 2015 the Company reported a net loss of $4,796,030, or a net loss per share of $0.13, compared to a net income of $3,129,348, or a net income per share of $0.10 for the twelve months ended June 30, 2014. The income from 2014 was due to the revaluation of our derivative liability. During the twelve months ended June 30, 2015 the Company has reduced its derivative liability from approximately $3.3 million at June 30, 2014 to approximately $1.0 million at June 30, 2015 through warrant exercises and exchanges.

The Company ended the 2015 fiscal year with approximately $1.75 million of cash and cash equivalents. Subsequent to the 2015 fiscal year end, the company announced the closing of a registered direct placement with $2.6 million in gross proceeds received from the offering.

Based on management’s current projections, the Company has enough capital to fund its operations into the third quarter of 2016.

Novartis receives EU approval for Farydak®, the first in its class of anticancer agents approved for patients with multiple myeloma

On September 4, 2015 Novartis reported that the European Commission has approved Farydak (panobinostat, previously known as LBH589) capsules, in combination with bortezomib* and dexamethasone, for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD) (Press release, Novartis, SEP 4, 2015, View Source [SID:1234507398]). The approval of Farydak marks the first time a histone deacetylase (HDAC) inhibitor with epigenetic activity is available in the European Union (EU), providing a new treatment option for patients living with multiple myeloma whose disease has progressed after standard-of-care therapy[1,2].

"Farydak is a welcome advance for people living with relapsed and/or refractory multiple myeloma in Europe," said Philippe Moreau, MD, Department of Hematology, Centre Hospitalier Universitaire de Nantes, France. "Patients with multiple myeloma often relapse or stop responding to treatments; Farydak offers a new mechanism of action, which may improve the effectiveness of response to standard-of-care treatment in patients."

Multiple myeloma is a cancer of the plasma cells, a type of white blood cell present in the bone marrow, and affects approximately 84,000 people in Europe[3,4]. Farydak is the first HDAC inhibitor to show efficacy in multiple myeloma[5]. As an HDAC inhibitor, its epigenetic activity may help restore cell function in patients with multiple myeloma[2].

The EU approval of Farydak is based on efficacy and safety data in a subgroup analysis of 147 patients who had received at least two prior regimens, including bortezomib and an IMiD, during the Phase III, randomized, double-blind, placebo-controlled, multicenter global registration trial, called PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA), evaluating Farydak in combination with bortezomib and dexamethasone against bortezomib and dexamethasone alone in patients with relapsed and/or relapsed and refractory multiple myeloma. The trial found that the median progression-free survival (PFS) benefit in this subgroup increased by 7.8 months in Farydak patients who had received prior treatment with both bortezomib and an IMiD (12.5 months; n=73), as compared to the placebo arm (4.7 months; n=74) (hazard ratio=0.47 [95% confidence interval (CI): 0.31, 0.72])[1].

The most common non-hematological adverse reactions included diarrhea, fatigue, nausea and vomiting. Treatment-emergent hematological toxicities included thrombocytopenia, anemia, neutropenia and lymphopenia. QTc prolongation of >480 and <500 msec was recorded in 1.3% of patients and change from baseline of >60 msec was observed in 0.8% of patients. No patients had an absolute QTc prolongation of >500 msec. Cardiac events (most frequently atrial fibrillation, tachycardia, palpitation and sinus tachycardia) were reported in 17.6% of the Farydak-treated patients versus 9.8% of placebo-treated patients and syncope events were reported in 6.0% versus 2.4%. Discontinuation due to adverse events (AEs), regardless of causality, was observed in 36.2% of patients. The most common AEs leading to treatment discontinuation were diarrhea (4.5%), asthenia and fatigue (2.9% each) and pneumonia (1.3%). On treatment deaths not due to the study indication (multiple myeloma) were reported in 6.8% of Farydak-treated patients versus 3.2% of placebo-treated patients[1].

"With the approval of Farydak in the European Union, we hope to address critically important treatment needs faced by the multiple myeloma community-disease progression and treatment resistance," said Bruno Strigini, President, Novartis Oncology. "This milestone, the approval of a first in its class treatment option for patients in need of new therapies, is the result of more than 13 years of dedicated research, which has helped us better understand the development of multiple myeloma."

Farydak in combination with bortezomib and dexamethasone is also approved in the US, Chile and Japan for certain patients with previously treated multiple myeloma. The exact indication for Farydak varies by country. In the US, Farydak is approved in combination with bortezomib and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior regimens, including bortezomib and an IMiD. Continued approval in the US may be contingent upon verification and description of clinical benefit in confirmatory trials.

About multiple myeloma
Multiple myeloma impacts approximately 84,000 people in Europe[4]. Multiple myeloma is a cancer of the plasma cells, a kind of white blood cell present in bone marrow-the soft, blood-producing tissue that fills the center of most bones. The cancer is caused by the production and growth of abnormal cells within the plasma, which multiply and build up in the bone marrow, pushing out healthy cells and preventing them from functioning normally[3]. Multiple myeloma is an incurable disease with a high rate of relapse (when the cancer returns) and resistance (when the therapy stops working)[6]. Standard-of-care regimens of proteasome inhibitors and IMiDs are often used to treat multiple myeloma, but most patients will stop responding to these treatments creating an unmet need for new options with novel mechanisms of action[6,7,8]. Multiple myeloma typically occurs in individuals 60 years of age or older, with few cases in individuals younger than 40[9].

About the PANORAMA Clinical Trial Program
PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA) is a Phase III, randomized, double-blind, placebo-controlled, multicenter global registration trial to evaluate panobinostat in combination with bortezomib and dexamethasone against bortezomib and dexamethasone alone in patients with relapsed or relapsed and refractory multiple myeloma who failed on at least one prior treatment. The study of 768 patients took place in 215 clinical trial sites worldwide making it the largest global registration trial for multiple myeloma to date. The primary endpoint of the trial was PFS. Data for overall survival, the key secondary endpoint of the trial, are not yet mature. Other secondary endpoints include overall response rate, duration of response and safety[10].

Farydak Important Safety Information
Farydak can cause serious side effects, including diarrhea and heart problems.

Diarrhea is common with Farydak and can be severe. Patients should tell their healthcare provider (HCP) right away if they have abdominal (stomach) cramps, loose stool, diarrhea, or feel like they are becoming dehydrated. HCPs may prescribe medicines to help prevent or treat these side effects. Taking or using stool softeners or laxative medicines may worsen diarrhea, patients should talk to their HCP before taking or using these medicines.

Farydak can cause severe heart problems which can lead to death. Risk of heart problems may be increased with a condition called "long QT syndrome" or other heart problems. Patients should call their HCP and get emergency medical help right away if they have any of the following symptoms of heart problems: chest pain, faster or slower heart beat, palpitations (feel like heart is racing), feel lightheaded or faint, dizziness, blue colored lips, shortness of breath, or swelling in legs.

Farydak can cause severe bleeding which can lead to death. It may take patients longer than usual to stop bleeding while taking Farydak. Patients should tell their HCP right away if they get any of the following signs of bleeding: blood in stools or black stools (look like tar), pink or brown urine, unexpected bleeding or bleeding that is severe or that cannot be controlled, vomit blood or vomit looks like coffee grounds, cough up blood or blood clots, increased bruising, feeling dizzy or weak, confusion, change in speech, or headache that lasts a long time.

Farydak is a prescription medicine used, in combination with bortezomib and dexamethasone, to treat people with a type of cancer called multiple myeloma after at least two other types of treatment have been tried. It is not known if Farydak is safe and effective in children.

Patients should tell their HCP about all of the medicines they take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

Patients should take Farydak exactly as the HCP tells them to take it. The HCP will tell patients how much Farydak to take and when to take it. The HCP may change the dose or stop treatment temporarily if patients experience side effects. Patients should not change the dose or stop taking Farydak without first talking with their HCP.

Patients should avoid eating star fruit, pomegranate or pomegranate juice, and grapefruit or grapefruit juice while taking Farydak. These foods may affect the amount of Farydak in the blood.

Low blood cell counts are common with Farydak and can be severe. Low platelet count (thrombocytopenia) can cause unusual bleeding or bruising under the skin. Low white blood cell count (neutropenia) can cause infections. Low red blood cell count (anemia) may make a patient feel weak, tired, or they may get tired easily, look pale, or feel short of breath.

There is an increased risk of infection while taking Farydak. Patients should contact their HCP right away if they have a fever or have any signs of an infection including sweats or chills, cough, flu-like symptoms, shortness of breath, blood in phlegm, sores on body, warm or painful areas on body, or feeling very tired.

Patients should call their HCP right away with any of the following symptoms of liver problems: feel tired or weak, loss of appetite, dark amber colored urine, upper abdominal pain, yellowing of skin or the white of eyes.

The most common side effects of Farydak include tiredness, nausea, swelling in arms or legs, decreased appetite, fever and vomiting. Patients should tell their HCP if they have any side effect that is bothersome or that does not go away.

* Trade name Velcade registered to Millennium Pharmaceuticals, Inc.

10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

(Filing, 10-K, DelMar Pharmaceuticals, SEP 3, 2015, View Source [SID:1234507396])