On June 23, 2016 Mateon Therapeutics, Inc. (Nasdaq:MATN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported that it has enrolled the first patient into its FOCUS Study, a phase 2/3 clinical trial of CA4P for the treatment of patients with platinum-resistant ovarian cancer (Press release, Mateon Therapeutics, JUN 23, 2016, View Source [SID:1234513521]). The FOCUS Study is designed to demonstrate whether the addition of CA4P to bevacizumab and chemotherapy, the current standard of care for platinum-resistant ovarian cancer, improves treatment outcomes for these patients. Schedule your 30 min Free 1stOncology Demo! "The initiation of the FOCUS Study is an important achievement for the company," stated William D. Schwieterman, M.D., President and Chief Executive Officer of Mateon. "Building upon the results of the GOG-0186I study recently published in the Journal of Clinical Oncology, we have designed this trial to be the one that we believe is most likely to lead to an FDA approval for CA4P in the shortest time possible. I look forward to providing updates as the trial progresses."
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The FOCUS Study has two stages. In the first stage the company plans to enroll up to 80 patients and conduct regular interim analyses to verify the safety and efficacy of the drug combination and to confirm powering assumptions for the second stage. In the second stage, which would support a New Drug Application (NDA) if positive, the company plans to enroll up to 356 patients without any planned interim analyses. The primary endpoint of the FOCUS Study is progression free survival (PFS). The company will also evaluate CA4P’s effect on objective response rate (ORR), overall survival (OS) and other parameters.
For further information about the clinical trial, please visit www.clinicaltrials.gov, Study NCT02641639.
Mateon reminds investors that it plans to hold an event to describe advances in ovarian cancer treatment, including updated data from the GOG-0186I Study in recurrent ovarian cancer, on Monday, June 27, 2016 at 12:00 pm at the Lotte New York Palace Hotel, with presentations expected to begin at approximately 12:15 pm eastern time. To listen to a webcast, please visit the company’s website, www.mateon.com – under the "Investors & News" tab, select the link to "Events & Presentations." A replay of the webcast will be available after the conclusion of the live event.
Author: [email protected]
Genmab Provides Update on Marketing Authorization Application for Arzerra® (ofatumumab) as Maintenance Therapy for Patients with Relapsed CLL
On June 23, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a negative opinion for the use of Arzerra (ofatumumab) as maintenance therapy for patients with relapsed chronic lymphocytic leukemia (CLL) (Press release, Genmab, JUN 23, 2016, View Source [SID:1234513520]). The Marketing Authorization Application (MAA) was submitted by Novartis in July 2015 under the ofatumumab collaboration between Novartis and Genmab.
“We are disappointed that we did not receive a positive recommendation for Arzerra in the maintenance CLL setting in Europe. We will continue to work with Novartis to define the best path forward for Arzerra,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
The MAA was based on positive data from an interim analysis from the Phase III PROLONG study (OMB112517), which evaluated ofatumumab maintenance therapy versus no further treatment in patients with a complete or partial response after second or third line treatment for CLL.
Safety and Efficacy Data from the Phase III PROLONG study
A total of 474 patients were included in the analysis. Patients who received ofatumumab maintenance treatment lived 14.2 months longer without their disease worsening than patients who received no further treatment. Median progression free survival (PFS) as assessed by the investigators was 29.4 months for the ofatumumab treatment arm, and 15.2 months for the observation arm (Hazard Ratio 0.50; p<0.0001).
There were no unexpected safety findings. The most common adverse reactions (≥10%) were infusion reactions, neutropenia, and upper respiratory tract infection. The two most common grade 3-4 adverse events were neutropenia (22% in ofatumumab arm vs 8% in observation arm), and pneumonia (5% in ofatumumab arm vs 3% in observation arm). During the period between the first dose and 60 days after the last dose there were two patients (1%) in the ofatumumab group and five patients (2%) in the observation group who died due to adverse events.
About the Phase III PROLONG study
This Phase III study was designed to randomize up to 532 patients with relapsed CLL who have responded to treatment at relapse, to either ofatumumab maintenance treatment or no further treatment (observation). Patients in the ofatumumab arm received an initial dose of 300 mg of ofatumumab, followed one week later by a second dose of 1,000 mg, then doses of 1,000 mg every 8 weeks for up to two years, while patients in the observation treatment arm received no further treatment.
The primary endpoint of the study was PFS. Secondary objectives were evaluation of clinical benefit, overall survival, safety, tolerability, the health-related quality of life of subjects treated with ofatumumab versus no further treatment, and pharmacokinetics among relapsed CLL patients receiving maintenance therapy with ofatumumab.
About CLL
CLL is the most commonly diagnosed adult leukemia in Western countries, and accounts for approximately 1 in 4 cases of leukemia.1 Most CLL patients experience disease progression despite initial response to therapy and may require additional treatment.2
About Ofatumumab (Arzerra)
Ofatumumab is a human monoclonal antibody that is designed to target the CD20 molecule found on the surface of chronic lymphocytic leukemia (CLL) cells and normal B lymphocytes.
In the United States, Arzerra is approved for use in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate and for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL. In the European Union, Arzerra is approved for use in combination with chlorambucil or bendamustine for the treatment of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy. In more than 50 countries worldwide, Arzerra is also indicated as monotherapy for the treatment of patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab.
Please see full Prescribing Information, including Boxed WARNING for Arzerra (ofatumumab).
Arzerra is marketed under a collaboration agreement between Genmab and Novartis. Novartis has rights to develop ofatumumab in autoimmune indications, including multiple sclerosis.
Genmab Provides Update on Marketing Authorization Application for Arzerra® (ofatumumab) as Maintenance Therapy for Patients with Relapsed CLL
On June 23, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a negative opinion for the use of Arzerra (ofatumumab) as maintenance therapy for patients with relapsed chronic lymphocytic leukemia (CLL) (Press release, Genmab, JUN 23, 2016, View Source [SID:1234513520]). Schedule your 30 min Free 1stOncology Demo! The Marketing Authorization Application (MAA) was submitted by Novartis in July 2015 under the ofatumumab collaboration between Novartis and Genmab.
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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
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"We are disappointed that we did not receive a positive recommendation for Arzerra in the maintenance CLL setting in Europe. We will continue to work with Novartis to define the best path forward for Arzerra," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
The MAA was based on positive data from an interim analysis from the Phase III PROLONG study (OMB112517), which evaluated ofatumumab maintenance therapy versus no further treatment in patients with a complete or partial response after second or third line treatment for CLL.
Safety and Efficacy Data from the Phase III PROLONG study
A total of 474 patients were included in the analysis. Patients who received ofatumumab maintenance treatment lived 14.2 months longer without their disease worsening than patients who received no further treatment. Median progression free survival (PFS) as assessed by the investigators was 29.4 months for the ofatumumab treatment arm, and 15.2 months for the observation arm (Hazard Ratio 0.50; p<0.0001).
There were no unexpected safety findings. The most common adverse reactions (≥10%) were infusion reactions, neutropenia, and upper respiratory tract infection. The two most common grade 3-4 adverse events were neutropenia (22% in ofatumumab arm vs 8% in observation arm), and pneumonia (5% in ofatumumab arm vs 3% in observation arm). During the period between the first dose and 60 days after the last dose there were two patients (1%) in the ofatumumab group and five patients (2%) in the observation group who died due to adverse events.
About the Phase III PROLONG study
This Phase III study was designed to randomize up to 532 patients with relapsed CLL who have responded to treatment at relapse, to either ofatumumab maintenance treatment or no further treatment (observation). Patients in the ofatumumab arm received an initial dose of 300 mg of ofatumumab, followed one week later by a second dose of 1,000 mg, then doses of 1,000 mg every 8 weeks for up to two years, while patients in the observation treatment arm received no further treatment.
The primary endpoint of the study was PFS. Secondary objectives were evaluation of clinical benefit, overall survival, safety, tolerability, the health-related quality of life of subjects treated with ofatumumab versus no further treatment, and pharmacokinetics among relapsed CLL patients receiving maintenance therapy with ofatumumab.
About CLL
CLL is the most commonly diagnosed adult leukemia in Western countries, and accounts for approximately 1 in 4 cases of leukemia.1 Most CLL patients experience disease progression despite initial response to therapy and may require additional treatment.2
About Ofatumumab (Arzerra)
Ofatumumab is a human monoclonal antibody that is designed to target the CD20 molecule found on the surface of chronic lymphocytic leukemia (CLL) cells and normal B lymphocytes.
In the United States, Arzerra is approved for use in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate and for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL. In the European Union, Arzerra is approved for use in combination with chlorambucil or bendamustine for the treatment of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy. In more than 50 countries worldwide, Arzerra is also indicated as monotherapy for the treatment of patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab.
Please see full Prescribing Information, including Boxed WARNING for Arzerra (ofatumumab).
Arzerra is marketed under a collaboration agreement between Genmab and Novartis. Novartis has rights to develop ofatumumab in autoimmune indications, including multiple sclerosis.
First-in-class Immunometabolic Modulator, PAK4/NAMPT Inhibitor, to be Evaluated in Patients with Advanced Solid Malignancies or Non-Hodgkin’s Lymphoma
On June 22, 2016 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company reported dosing of the first patient in a Phase 1 clinical trial evaluating KPT-9274, an oral, first-in-class, dual-acting p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, in patients with advanced solid malignancies (including sarcoma, colon and lung cancer) or non-Hodgkin’s lymphoma (NHL) whose disease has relapsed after standard therapy(s) (NCT02702492) (Press release, Karyopharm, JUN 22, 2016, View Source [SID1234517065]).
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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
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This first-in-human, multi-center, open-label, dose-escalation trial is expected to enroll up to 175 patients. The primary endpoints of this study are to determine the recommended Phase 2 dose (RP2D) and the maximum tolerated dose (MTD) of KPT-9274 administered alone and with extended release niacin, and to evaluate safety and tolerability. The key secondary endpoint is to assess anti-tumor activity in patients predicted to be more sensitive to PAK4/NAMPT inhibition, including those with NAPRT-deficient tumors and tumors harboring IDH1 mutations.
"Our first-in-class, oral, small molecule PAK4 and NAMPT modulator, KPT-9274, has synergistic anti-tumor effects through several mechanisms including immune cell activation by inhibiting ß-catenin, reduction of NAD levels which tumor cells use as a key energy source, blockade of DNA damage repair mechanisms, and induction of tumor cell apoptosis," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "We are encouraged by the preclinical profile of KPT-9274, highlighted at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) and 2016 American Association of Cancer Research annual meetings, which support the novel mechanism and demonstrated encouraging preclinical anti-tumor activity. To our knowledge, we are the only company with a compound in clinical development that directly targets both PAK4 and NAMPT. This important Phase 1 study will continue to build upon the body of scientific evidence supporting KPT-9274’s safety and efficacy, and we look forward to reporting top-line data next year."
This Phase 1 clinical study is supported by extensive preclinical data demonstrating KPT-9274’s anti-cancer activity against hematological and solid tumors while showing minimal toxicity to normal cells in vitro. Preclinical studies demonstrate that by blocking PAK4, KPT-9274 potently inhibits ß-catenin as well as certain Ras oncogene-dependent pathways. ß-catenin is believed to be a key mediator of immune suppression, including resistance to immune-activating therapies. In addition, both ß-catenin and Ras are key growth signaling pathways for many common tumors such as colon and lung cancers. NAMPT, which can be found in a complex with PAK4 within the cell, is a pleiotropic protein with intra- and extra-cellular functions as an enzyme, cytokine, growth factor and hormone, and is thought to play a role in cellular energy metabolism. Hematologic and solid tumor cells become dependent on both PAK4 and NAMPT pathways and are therefore susceptible to single-agent cytotoxicity by KPT-9274. In mouse and rat xenograft studies, orally administered KPT-9274 showed robust anti-cancer activity with favorable tolerability. Based on in vitro and in vivo activity, Karyopharm believes KPT-9274 holds significant potential for the treatment of a wide variety of both solid and hematological cancers.
About KPT-9274
KPT-9274 is a first-in-class, orally bioavailable, small molecule immunometabolic modulator that works through non-competitive dual inhibition of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). Co-inhibition of these targets is believed to lead to synergistic anti-tumor effects through suppression of ß-catenin by blocking PAK4, leading to both immune cell activation and inhibition of tumor growth, energy depletion through NAMPT inhibition, blockade of DNA repair, cell cycle arrest and ultimately apoptosis. KPT-9274 may therefore have both immune-activating and direct antitumor effects. In contrast, normal cells are less sensitive to inhibition by KPT-9274 due in part to their relative genomic stability and lower metabolic demands.
Nymox Reports Long-Term Prostate Cancer Results in 7 Year Prospective Study of 995 U.S. Middle-Aged and Elderly Men Without Cancer
On June 22, 2016 Nymox Pharmaceutical Corporation (NASDAQ:NYMX) reported results from the Company’s 7 year prospective placebo controlled double blind studies of treatment of 995 U.S. men with the Company’s lead drug fexapotide (Press release, Nymox, JUN 22, 2016, View Source;fvtc=4&fvtv=6907 [SID:1234513492]). Men who received fexapotide showed a major reduction in the incidence of prostate cancer, compared to placebo and compared to the known and expected normal incidence of the disease.
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The men in the study received fexapotide or placebo for the treatment of their prostate enlargement (BPH) symptoms. All men were thoroughly evaluated to exclude any prostate cancer prior to qualifying for enrollment in the studies. The participants were enrolled at over 70 top well-known U.S. urological investigational centers, and were followed for up to 7 years (median of 5 years) after treatment. The study analyzed all cases of prostate cancer that were subsequently diagnosed. The expected rate of new prostate cancer in the U.S. general male population in this age group is in the 5-20% range after 7 years. In the BPH population in published large trials of drugs for the prevention of prostate cancer, the incidence of new prostate cancer cases after 4-7 years has been reported in major studies to be 20-25%. The new data analysis from the Nymox fexapotide study has now shown the statistically significant and very low incidence of 1.3% for prostate cancer in this comparable fexapotide treated BPH population.
"These results are astonishingly good. Other drug treatments and controls tested in similar studies have been associated with a prostate cancer incidence 10 times higher than the results reported today by Nymox for fexapotide. This is truly good news. The data strongly indicate that in addition to benefit for BPH symptoms, fexapotide will also help to prevent cancer in these patients," said Dr. Ronald Tutrone, one of the Principal Investigators in the Nymox Fexapotide Prostate Cancer and BPH studies. Dr. Tutrone is Chief of the Division of Urology, Greater Baltimore Medical Center; Medical Director of Chesapeake Urology Research Associates and Chairman of the William E. Kalhert Endowment for Urological Research.
Fexapotide is a safe and painless single injection treatment given in the urologist’s office. The drug is in Phase 3 for BPH and Phase 2 for prostate cancer. It has been tested in over 1700 drug and placebo treatment administrations in the U.S. As a treatment for BPH, fexapotide shows long-term efficacy without the safety risk and side effect concerns or added cancer risk associated with currently approved BPH treatments. As a treatment for prostate cancer fexapotide was found to lead to highly statistically significant reduction in disease progression in a large 147 patient multi-year Phase 2 study of U.S. men with low grade cancer.
Dr. Paul Averback, CEO of Nymox said, "The new results now add a third dimension to fexapotide utility: clinical prostate cancer prevention. The drug has now demonstrated statistically significant prospective long-term outcome data showing dramatic reduction in the incidence of newly diagnosed prostate cancer after minimal BPH treatment with fexapotide. Nymox announced in Q3 last year that it will seek regulatory approvals for fexapotide for BPH based on the long-term BPH safety and efficacy data announced Q3 last year. We believe that the exciting new prostate cancer prevention results reported today will add to the evidence in fexapotide’s favor towards our goal of widespread major benefit for middle-aged and elderly men."
Dr. Averback added, "We are extremely grateful to the thousands of people who have been part of these clinical trials. The Company also thankfully acknowledges our shareholders for their long-term commitment that supports these studies."