On September 15, 2016 Celsion Corporation (NASDAQ:CLSN) reported that the independent Data Safety Monitoring Board (DSMB) has completed its safety review of data from the first three patient cohorts in the ongoing Phase Ib OVATION Study (Press release, Celsion, SEP 15, 2016, View Source [SID:SID1234515152]). Based on the DSMB’s recommendation, the study will continue as planned and the Company will proceed with dosing in its fourth and final patient cohort at an escalated dose. The OVATION Study is a dose-escalating clinical trial combining GEN-1, the Company’s DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with advanced ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery. Schedule your 30 min Free 1stOncology Demo! "The DSMB’s recommendation and the lack of any dose limiting toxicities in the trial to date underscore the improved tolerability of GEN-1 over recombinant IL-12 protein-based therapies," said Nicholas Borys, M.D., senior vice president and chief medical officer of Celsion. "The favorable safety profile we have seen thus far is consistent with the translational data that we reported earlier this year, which show that GEN-1 produces a sustained, localized secretion of IL-12 protein and avoids the high levels of systemic exposure which have limited the development of recombinant IL-12 therapies in the past."
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!
"We could not be more excited to progress with the OVATION Study and look forward to reporting clinical findings from the third patient cohort, as well as translational data from the first two cohorts, early in the fourth quarter. Furthermore, we expect to report final data from this highly promising study in the first quarter of 2017," said Michael H. Tardugno, Celsion’s chairman, CEO and president. "We have been encouraged, as have been our Investigators, by the findings to-date in this difficult-to-treat patient population. As we have previously reported, all six patients in the first two cohorts experienced a clinically meaningful response, ranging from stable disease to one pathologically confirmed complete response. In addition, we saw sustained decreases of 90% or greater of the prospective indicator of the presence of ovarian cancer cells, CA-125 protein, in all patients, as well as highly impressive pathologically responses, which is associated with prolonged survival."
The OVATION Study is designed to enroll three to six patients per dose cohort at escalating doses of GEN-1 with the goal to identify a safe, tolerable and therapeutically active dose of GEN-1 by recruiting and maximizing an immune response. The first three cohorts each enrolled three patients. Enrollment in the fourth and final cohort is underway, and Celsion expects to report full data from the OVATION Study by the first quarter of 2017. Future studies of GEN-1 will include a Phase I/II study combining GEN-1 with Avastin and Doxil.
Year: 2016
ArQule Announces Publication of Manuscript Highlighting Preclinical Activity of FGFR Inhibitor, ARQ 087, in Peer Reviewed Journal
On September 15, 2016 ArQule, Inc. (Nasdaq: ARQL) reported the publication of a paper detailing the preclinical profile of ARQ 087, an orally available fibroblast growth factor receptor (FGFR) inhibitor (Press release, ArQule, SEP 15, 2016, View Source [SID:SID1234515151]). The findings, published on-line by PLOS ONE, View Source, demonstrate that ARQ 087 has anti-proliferative activity in cell lines driven by FGFR dysregulation, including amplifications, fusions, and mutations.
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!
ARQ 087 is being dosed in intrahepatic cholangiocarcinoma (iCCA) patients with FGFR2 genetic alterations as part of the phase 2 portion of a biomarker driven phase 1/2 trial. The company has been granted orphan drug designation by the U.S. Food and Drug Administration and European Medicines Agency for ARQ 087 in this indication.
About Intrahepatic Cholangiocarcinoma
Cholangiocarcinoma (CCA) is the most common biliary malignancy and the second most common hepatic malignancy after hepatocellular carcinoma (HCC)1. Depending on the anatomic location, CCA is classified as intrahepatic (iCCA), perihilar (pCCA), and extrahepatic (eCCA). iCCA originates from the intrahepatic biliary ductal system and forms an intrahepatic mass. The average age adjusted incidence rate for iCCA is approximately one in 100,000 per year in the United States and Europe2,3.
About FGFR and ARQ 087
ARQ 087 is a multi-kinase inhibitor designed to preferentially inhibit the fibroblast growth factor receptor ("FGFR") family with demonstrated activity in FGFR2 genetic alterations. The FGFR pathway is disrupted in several ways in human cancer, thus providing numerous therapeutic targets for an inhibitor of this pathway. ARQ 087 has demonstrated in vivo inhibition of tumor growth and downstream signaling in tumors whose growth is driven by FGFR targets.
Signals of single agent activity with this drug were observed in phase 1a testing. Phase 1b expansion cohorts with ARQ 087 include patients with cholangiocarcinoma and adrenocortical tumors, as well as those with FGFR translocations, amplifications and mutations. Clinical development of ARQ 087 has advanced into phase 2 for intrahepatic cholangiocarcinoma (iCCA) following the observation of two confirmed responses in this patient population in the phase 1 portion of the program.
EISAI RECEIVES LICENSE FOR NEW INDICATION FOR ANTICANCER AGENT KISPLYX(R) ? (LENVATINIB MESYLATE) FOR TREATMENT OF ADVANCED RENAL CELL CARCINOMA
On September 15, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that its European regional headquarters Eisai Europe Ltd. (Location: U.K.) has received license from the European Commission for anticancer agent Kisplyx ▼ (generic name: lenvatinib mesylate, "lenvatinib") in combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma following one prior vascular endothelial growth factor (VEGF) targeted therapy (Press release, Eisai, SEP 15, 2016, View Source [SID:SID1234515149]). Following the United States, Europe marks the second region where lenvatinib has been licensed for the advanced renal cell carcinoma indication. Schedule your 30 min Free 1stOncology Demo! This license was based on a Phase II clinical study (Study 205)1 that evaluated the safety and efficacy of lenvatinib in combination with everolimus in patients with unresectable advanced or metastatic renal cell carcinoma following one prior VEGF-targeted therapy. From the results of the study, the lenvatinib plus everolimus group (n=51) demonstrated a significant extension in the study’s primary endpoint of progression free survival (PFS) compared to the everolimus alone group (n=50) (median PFS for the lenvatinib plus everolimus group: 14.6 months vs median PFS for the everolimus alone group: 5.5 months; Hazard Ratio (HR) 0.40 [95% CI: 0.24-0.68], p=0.0005). Furthermore, updated median overall survival in the study population was 25.5 months in the lenvatinib plus everolimus group compared with 15.4 months in the everolimus alone group (HR 0.59 [95% CI: 0.36-0.97]).2 The most common treatment-emergent adverse events (TEAEs) reported in the lenvatinib plus everolimus group were diarrhea, decreased appetite and fatigue. The most common TEAEs of Grade 3 or higher (Common Terminology Criteria for Adverse Events) were diarrhea, hypertension and fatigue.
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!
The number of patients with renal cancer is estimated to be approximately 338,000 worldwide, including approximately 115,000 in Europe, 58,000 in the United States and 17,000 in Japan.3 Renal cell carcinoma comprises more than 90% of all malignancies of the kidney,4 and originates from malignant cells in the lining of the tubules of the kidney. The incidence of renal cell carcinoma in people over 55 years of age is rising, and it is more likely to affect men than women. For advanced or metastatic renal cell carcinoma that is difficult to treat with surgery, the standard treatment is molecular targeted drug therapy, however with low 5-year survival rates, this remains a disease with significant unmet medical need.
In Europe, lenvatinib has been designated as an orphan drug for thyroid cancer and is marketed as Lenvima for this indication. In Europe, renal cell carcinoma does not meet the criteria for orphan drug designation. Accordingly, under European regulations, any licensed medicine that previously received orphan drug designation for an indication and subsequently receives license for a non-orphan indication must be marketed under a different trade name. As such, lenvatinib will be marketed as Kisplyx ▼ in the European Union for the indication covering renal cell carcinoma.
Eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. Eisai remains committed to providing further clinical evidence for lenvatinib aimed at maximizing value of the drug as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.
*Please refer to the following notes for the licensed indications in the United States, Japan and Europe
Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120
1. About lenvatinib mesylate (generic name, "lenvatinib")
Discovered and developed in-house, lenvatinib is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other proangiogenic and oncogenic pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor proliferation.
Currently, Eisai has obtained license for lenvatinib as a treatment for refractory thyroid cancer in over 45 countries including in the United States, Japan, in Europe, Korea, Canada, and Mexico, and has submitted applications for regulatory review in countries throughout the world including South Africa and Malaysia. Specifically, Eisai has obtained license for the agent indicated in the United States for treatment for locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer, in Japan for the treatment of unresectable thyroid cancer, and in Europe for the treatment of adult patients with progressive, locally advanced or metastatic differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine, respectively.
Furthermore, lenvatinib was also licensed in the United States in May 2016 for an additional indication in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy.
Meanwhile, Eisai is conducting clinical studies of lenvatinib in several other tumor types such as hepatocellular carcinoma (Phase III), endometrial carcinoma (Phase II), biliary tract cancer (Phase II), and in combination with an immune checkpoint inhibitor for various types of cancer (Phase Ib/II).
Lenvatinib is marketed globally for use in the treatment of thyroid cancer and also in the United States for use in the treatment of renal cell carcinoma under the brand name Lenvima. Lenvatinib has been designated as an orphan drug for thyroid cancer by the regulatory authorities in Japan, the United States and Europe. Under European regulations, any licensed medicine that previously received orphan drug designation for an indication and now received license for a non-orphan indication must be marketed under a different trade name. As such, lenvatinib will be marketed as Kisplyx ▼ in the European Union for the indication covering renal cell carcinoma.
About the Phase II Clinical Study (Study 205)1
Study 205 was a multicenter, randomized, open-label study of the combination of lenvatinib (18 mg) plus everolimus (5 mg), lenvatinib alone (24 mg), and everolimus alone (10 mg) in patients with unresectable advanced or metastatic renal cell carcinoma following one prior VEGF-targeted therapy, and was conducted in Europe and the United States. 153 patients were randomized in a 1:1:1 ratio to one of three treatment arms to compare the efficacy and safety of these three regimens.
From the results of the study, the combination of lenvatinib plus everolimus group demonstrated a significant extension in the study’s primary endpoint of progression free survival (PFS) compared to the everolimus alone group (median PFS for the lenvatinib plus everolimus group: 14.6 months vs median PFS for the everolimus alone group: 5.5 months; Hazard Ratio (HR) 0.40 [95% CI: 0.24-0.68], p=0.0005). Additionally, median PFS for the lenvatinib alone group was 7.4 months, demonstrating an extension in PFS compared to the everolimus alone group (HR: 0.61 [95% CI: 0.38-0.98]).
The study also assessed objective response rate (ORR) and overall survival (OS) as secondary endpoints. Regarding ORR, both the lenvatinib plus everolimus group and the lenvatinib alone group showed an improvement in ORR compared to the everolimus alone group (lenvatinib plus everolimus: 43%, lenvatinib alone: 27%, everolimus alone: 6%). Furthermore, regarding OS, updated median overall survival in the study population was 25.5 months in the lenvatinib plus everolimus group compared with 15.4 months in the everolimus group (HR 0.59; 95% CI 0.36 – 0.97).2
The most common any-grade treatment-emergent adverse events (TEAEs) reported in the lenvatinib plus everolimus group were diarrhea, decreased appetite and fatigue. The most common TEAEs of Grade 3 or higher (Common Terminology Criteria for Adverse Events) were diarrhea, hypertension and fatigue.
10-Q – Quarterly report [Sections 13 or 15(d)]
Champions Oncology has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .
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!
Allergan to Acquire Vitae Pharmaceuticals Adding Innovative Development Programs for Dermatologic Conditions
On September 14, 2016 Allergan plc (NYSE: AGN), a leading global pharmaceutical company, and Vitae Pharmaceuticals, Inc. (NASDAQ: VTAE), a clinical-stage biotechnology company, reported that they have entered into a definitive agreement under which Allergan will acquire Vitae for $21.00 per share, in cash, for a total transaction value of approximately $639 million (Press release, Allergan, SEP 14, 2016, View Source [SID1234523885]). The Boards of Directors of both companies have unanimously approved the transaction.
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!
The acquisition will strengthen Allergan’s dermatology product pipeline, with the addition of VTP-43742, a Phase 2 first-in-class, orally active RORγt (retinoic acid receptor-related orphan receptor gamma) inhibitor for the potential treatment of psoriasis and other autoimmune disorders. VTP-43742 acts through the potent inhibition of IL-17 activity. In preclinical studies, VTP-43742 has been observed to inhibit RORγt activity, is highly selective versus other ROR isotypes and may provide a treatment that could be administered as a once-daily oral dose. The compound recently completed a Phase 2 proof-of-concept multiple ascending dose trial in patients with moderate to severe psoriasis.
The acquisition also adds VTP-38543, a topical LXRβ (Liver X Receptor beta) selective agonist for the potential treatment of atopic dermatitis. It is believed that VTP-38543 works by decreasing inflammation in damaged skin tissue and repairing the damaged outer layer of skin. VTP-38543 is currently in a Phase 2a proof-of-concept clinical trial assessing the safety, tolerability and efficacy in patients with mild to moderate atopic dermatitis.
Vitae has developed and utilizes its Contour structure-based drug design platform to discover product candidates for validated therapeutic targets where biopharmaceutical research and development has traditionally struggled to develop drugs due to challenges related to potency, selectivity and pharmacokinetics. This has provided Vitae’s R&D team the ability to create first-in-class product candidates for challenging therapeutic targets.
"The acquisition of Vitae is a strategic investment for Allergan that adds strength and depth to our innovative medical dermatology franchise," said Brent Saunders, CEO and President of Allergan. "Vitae has pioneered the discovery and development of highly differentiated first-in-class compounds in atopic dermatitis, psoriasis and autoimmune diseases, areas of medicine where innovation is needed for patients."
"The Vitae team has been tremendously successful in discovering and conducting early development work in areas of medicine that can benefit from significant innovation," said Jeff Hatfield, President and Chief Executive Officer of Vitae. "Allergan has a long track record in developing and commercializing innovative dermatologic treatments. I believe our programs will be poised for successful development as part of Allergan’s portfolio. I am very proud of the tremendous contributions of our research teams and the clinical community who have led the discovery and development of our pipeline programs, and I thank them for their dedication to this science that may one day help many patients with dermatologic conditions, autoimmune disorders and potentially other conditions."
"Both the VTP-43742 and VTP-38543 programs offer the potential for highly differentiated mechanisms of action for the treatment of dermatologic conditions where patients are underserved by currently approved treatments," said David Nicholson, Chief Research & Development Officer, Allergan. "In addition, Vitae’s novel Contour drug discovery platform and its team, which have been instrumental in the discovery of novel ‘difficult to drug’ compounds, will be highly complementary to Allergan’s existing R&D discovery efforts in key therapeutic areas."
Under the terms of the merger agreement, a subsidiary of Allergan will commence a cash tender offer to purchase all of the outstanding shares of Vitae common stock for $21.00 per share. The closing of the tender offer is subject to customary closing conditions, including U.S. antitrust clearance and the tender of a majority of the outstanding shares of Vitae common stock. The merger agreement contemplates that Allergan will acquire any shares of Vitae that are not tendered into the offer through a second-step merger, which will be completed promptly following the closing of the tender offer. Pending approvals, Allergan anticipates closing the transaction by the end of 2016.
Additional information about Vitae, VTP-43742 and VTP-38543, as well as the unmet medical need in the treatment of psoriasis and atopic dermatitis, is available as a slide presentation on the Allergan web site at View Source
Debevoise & Plimpton LLP is serving as Allergan’s legal counsel. J.P. Morgan is serving as financial advisor to Vitae and Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP is serving as Vitae’s legal counsel.