On June 26, 2017 Eisai Co., Ltd. reported that it has submitted applications to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for its in-house discovered and developed anticancer agent lenvatinib mesylate (lenvatinib) for the treatment of hepatocellular carcinoma (HCC) (Press release, Eisai, JUL 26, 2017, View Source [SID1234528955]). This follows the application in Japan. Lenvatinib for the treatment of HCC is designated as an orphan drug by the FDA.

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This application is based on the results of the REFLECT study (Study 304), a multicenter, open-label, randomized, global Phase III trial comparing the efficacy and safety of lenvatinib versus sorafenib, a standard treatment for HCC, as a first-line treatment for 954 patients with unresectable HCC.(1)

In the REFLECT study, lenvatinib met the primary endpoint and demonstrated an overall survival (OS) treatment effect by the statistical confirmation of non-inferiority compared to sorafenib. Developing first-line treatments for HCC is challenging, and over the past 10 years, four previous first-line Phase III studies investigating other agents compared to sorafenib have failed to achieve this endpoint in OS.(2)

Additionally, lenvatinib showed highly statistically significant and clinically meaningful improvements in the secondary endpoints of Progression Free Survival (PFS), Time To Progression (TTP), and Objective Response Rate (ORR). In this study, the five most common adverse events observed in the lenvatinib arm were hypertension, diarrhea, decreased appetite, weight loss and fatigue, which is consistent with the known side-effect profile of lenvatinib.
Liver cancer is the second leading cause of cancer related death and is estimated to be responsible for 750,000 deaths per year globally (27,000 per year in the US, 62,000 per year in Europe), with 780,000 cases newly diagnosed each year (30,000 per year in the US, 63,000 per year in Europe).(3) HCC accounts for 85 percent to 90 percent of liver cancer cases. Treatment options for unresectable HCC are limited and the prognosis is very poor, making this an area of high unmet medical need.

Lenvatinib is approved as a treatment for refractory thyroid cancer in over 50 countries, including the United States, Japan, and in Europe, under the brand name Lenvima. Additionally, lenvatinib in combination with everolimus is approved for the treatment of renal cell carcinoma (RCC) in over 35 countries, including the United States and in Europe. In Europe, lenvatinib was launched under the brand name Kisplyx for RCC.

Eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. Eisai is committed to exploring the potential clinical benefits of lenvatinib 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.

About lenvatinib mesylate (generic name, "lenvatinib", product name: Lenvima/ Kisplyx)

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 PDGFRalpha; KIT; and RET) involved in tumor proliferation. Currently, Eisai has obtained approval for lenvatinib as a treatment for refractory thyroid cancer in over 50 countries, including the United States, Japan, and in Europe, under the brand name Lenvima. Additionally, Eisai has obtained approval for the agent in combination with everolimus as a treatment for renal cell carcinoma (second-line) in over 35 countries, including the United States and in Europe. In Europe, the agent was launched under the brand name Kisplyx for RCC. A Phase III study of lenvatinib in separate combinations with everolimus and pembrolizumab in renal cell carcinoma (first-line) was initiated and is underway. A Phase Ib/II study to investigate the agent in combination with pembrolizumab in select solid tumors (non-small cell lung cancer, renal cell carcinoma, endometrial cancer, urothelial cancer, head and neck cancer, and melanoma) and a Phase Ib study in HCC are also underway. Following the submission of applications in Japan (June 2017), the United States and Europe (July 2017), Eisai also plans to submit an application for lenvatinib for the treatment of HCC in China within the latter half of fiscal 2017.

About the RELECT study (Study 304)(1)

The REFLECT study (A Multicenter, Randomized, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib (E7080) Versus Sorafenib in First-Line Treatment of Subjects With Unresectable HCC) is a multicenter, open-label, randomized, global Phase III study comparing the efficacy and safety of lenvatinib versus sorafenib. In the study, 954 patients were randomized in a 1:1 ratio to receive lenvatinib 12 mg (=/>60 kg) or 8 mg (<60 kg) once a day, depending on baseline body weight (n= 478) or sorafenib 400 mg twice a day (n= 476). Treatment was continued until disease progression or unacceptable toxicity.

On July 26, 2017 Oncolytics Biotech Inc. (Oncolytics or the Company) (TSX:ONC) (OTCQX:ONCYF) reported that two abstracts describing both pooled safety and tolerability data and the mechanism of REOLYSIN, also known as pelareorep, have been selected for poster presentation (display) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress (Press release, Oncolytics Biotech, JUL 26, 2017, View Source [SID1234519895]). The abstracts will be published online on the ESMO (Free ESMO Whitepaper) website at 3:05 ET on Wednesday, August 30. The conference is taking place from September 8-12, 2017, in Madrid, Spain.

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"The pooled analysis of patients treated with intravenous pelareorep is the largest safety database available for this class of agents in combination with chemotherapy," said Dr. Andres Gutierrez, Chief Medical Officer at Oncolytics Biotech. "While our efficacy in metastatic breast cancer announced earlier this year at AACR (Free AACR Whitepaper) was captivating, the safety component of pelareorep increases the benefit-risk ratio of the therapy and supports its further development. We are particularly excited to present these results as other immuno-oncology agents in the same class have had limited or no experience with systemic administration."

Publication number: 1193P
Title: Pooled data analysis of the safety and tolerability of intravenous Pelareorep in combination with chemotherapy in 500 + cancer patients
Lead Author: Dr. Andres Gutierrez, Oncolytics Biotech

Publication number: 523P
Title: Mechanism of Pelareorep (Pel)-mediated cell death in a Phase I study in combination with irinotecan/ fluorouracil/ leucovorin/ bevacizumab (FOLFIRI/B) in patients with KRAS mutant metastatic colorectal cancer (mCRC)
Lead Author: Dr. Sanjay Goel, Montefiore Medical Center, NY

The Company also announced that it has been granted an End-of-Phase 2 meeting with the United States Food and Drug Administration (FDA), taking place in August 2017. The meeting will address registration pathways for REOLYSIN for the treatment of metastatic breast cancer, the indication for which the FDA has granted Fast Track designation. The Company expects to announce the outcome of this meeting in the fourth quarter of 2017.

On July 25, 2017 HedgePath Pharmaceuticals, Inc. (OTCQX:HPPI), a clinical stage biopharmaceutical company that discovers, develops and plans to commercialize innovative therapeutics for patients with cancer, reported that the U.S. Food and Drug Administration (FDA) has provided further guidance regarding HPPI’s ongoing, open-label Phase 2(b) clinical trial studying the effect of SUBA-Itraconazole (SUBA-Cap) oral capsules in patients with Basal Cell Carcinoma Nevus Syndrome (BCCNS), also known as Gorlin Syndrome (Press release, HedgePath Pharmaceuticals, JUL 25, 2017, View Source [SID1234519943]).

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The FDA’s guidance came in the form of a written response by FDA to HPPI’s Type-C meeting background package. Such a meeting is a standard element of the regulatory review process leading to a potential New Drug Application (NDA) to FDA.

Nicholas Virca, President and CEO of HPPI, stated that, "We are pleased with the FDA’s guidance, since we believe it adds clarity to our regulatory and clinical road going forward for the BCCNS indication of SUBA-Cap. FDA confirmed that we may follow the more streamlined 505(b)(2) regulatory pathway, which will allow us to reference safety data from previous third-party itraconazole trials, to be supplemented by our own safety database. The acceptability of this combined safety database will then be determined by the FDA during the course of its review of the future NDA. FDA also agreed that no additional nonclinical toxicology studies appear necessary to support filing an NDA for SUBA-Itraconazole under the 505(b)(2) pathway."

Importantly, FDA also indicated that it "[w]ould accept a single study to support an NDA if results show a significant effect on a clinically meaningful endpoint. The results of the single trial must be sufficiently robust and so compelling that it would be unethical to repeat the study . . . [e]vidence of an objective reduction in tumor burden that is durable is important in order to demonstrate antitumor effects of SUBA-Itraconazole in patients with BCCNS and these data should be collected and independently reviewed."

Mr Virca further stated that, "In light of FDA’s additional guidance on what might constitute a clinically significant response, we are now undertaking further detailed analyses of individual tumor responses from our ongoing trial seeking to verify the robustness of our therapy in reducing the tumour burden in BCCNS patients. We intend to present the results of this additional analysis to FDA and continue discussions with them about the utility of such results in a potential NDA submission."

Readers are cautioned that no assurances can be given that (i) the final study results will match the results previously reported on May 30, 2017 or (ii) the study, when and if completed, will achieve its primary and secondary endpoints or (iii) that the study results will be found by FDA to be sufficient for the filing of a NDA, or that one or more additional studies will not be required or (iv) if an NDA is filed, that it will be approved by FDA. Further, HPPI is not committing to providing further interim updates prior to the reporting of the final study results.

About BCCNS
BCCNS results from a genetic mutation which causes the Hedgehog pathway (a major regulator of processes in cells) to function improperly, leading to the chronic formation of basal cell tumors, including potentially disfiguring lesions on the face. Industry sources estimate that there are approximately 10,000 patients in the United States with BCCNS, which has qualified SUBA-Itraconazole under the FDA’s Orphan Drug Designation Program.

About SUBA-Itraconazole
SUBA-Itraconazole is a patented and proprietary itraconazole formulation that enhances the absorption of itraconazole to improve the bioavailability of orally administered drugs that are poorly soluble. The U.S. rights to SUBA-Itraconazole for the treatment of cancer are exclusively licensed to HPPI by an affiliate of Mayne Pharma Group Limited. SUBA-Itraconazole was developed to improve absorption and significantly reduce variability compared to generic itraconazole. These benefits provide enhancements to patients and prescribers with reduced intra- and inter-patient variability, enabling a more predictable clinical response and a reduction in the active drug quantity to deliver the required therapeutic blood levels.

On July 25, 2017 RedHill Biopharma Ltd. (NASDAQ:RDHL) (Tel-Aviv Stock Exchange:RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company primarily focused on late clinical-stage development and commercialization of proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, reported its financial results for the quarter ended June 30, 2017 (Press release, RedHill Biopharma, JUL 25, 2017, View Source [SID1234519868]).

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The Company will host a conference call on Tuesday, July 25, 2017 at 9:00 am EDT to review the financial results and business highlights. Dial-in details are included below.

Financial highlights for the quarter ended June 30, 20172
Net Revenues for the second quarter of 2017 were approximately $0.5 million, compared to immaterial Net Revenues in the second quarter of 2016 and in the first quarter of 2017. The increase was due to the initiation, in mid-June 2017, of the U.S. promotional activities of Donnatal (Phenobarbital, Hyoscyamine Sulfate, Atropine Sulfate, Scopolamine Hydrobromide)3 and the sale of EnteraGam (serum-derived bovine immunoglobulin/protein isolate, SBI)4.

Cost of Revenues for the second quarter of 2017 were $0.3 million, reflecting costs related to the initiation of the sale of EnteraGam in mid-June 2017.

Research and Development Expenses for the second quarter of 2017 were $8.4 million, an increase of $2.4 million or 40% compared to the second quarter of 2016. The increase was mainly due to the ongoing Phase III and Phase II studies with BEKINDA (RHB-102) for gastroenteritis and IBS-D, respectively, the ongoing Phase III study with RHB-104 for Crohn’s disease, the ongoing and planned studies with YELIVA (ABC294640) for multiple indications, and the initiation of the ongoing confirmatory Phase III study with TALICIA (RHB-105)5 for H. pylori infection. Research and Development Expenses for the second quarter of 2017 increased by $0.3 million or 4% compared to the first quarter of 2017.

General and Administrative Expenses for the second quarter of 2017 were $1.9 million, an increase of $1.2 million compared to the second quarter of 2016. General and Administrative Expenses for the second quarter of 2017 increased by $0.6 million or 48% compared to the first quarter of 2017. The increase from the comparable periods was mainly due to the establishment and advancement of the Company’s U.S. commercial operations in the first quarter of 2017 and enhanced professional services.

Selling, Marketing and Business Development Expenses for the second quarter of 2017 were $3.4 million, an increase of $3.0 million compared to $0.4 million in the second quarter of 2016, comprised only of Business Development Expenses. The increase was mainly due to the establishment and advancement of the Company’s U.S. commercial operations. The Company recognized Selling and Marketing Expenses in 2017 for the first time.

Operating Loss for the second quarter of 2017 was $13.5 million, an increase of $6.3 million or 88% compared to the second quarter of 2016. The increase was mainly due to an increase in Research and Development Expenses and Selling, Marketing and Business Development Expenses, as detailed above. Operating Loss for the second quarter of 2017 increased by $3.4 million or 34% compared to the first quarter of 2017. The increase was mainly due to an increase in Selling, Marketing and Business Development Expenses, as detailed above.

Financial Income, net for the second quarter of 2017 was $2.5 million, an increase of $1.9 million compared to the second quarter of 2016. Financial Income, net for the second quarter of 2017 increased by $1.0 million or 67% compared to the first quarter of 2017. The increase from the comparable periods was mainly due to a fair value gain on derivative financial instruments.

Net Cash Used in Operating Activities for the second quarter of 2017 was $9.7 million, an increase of $4 million or 70% compared to the second quarter of 2016. The increase was mainly due to the increase in Operating Loss, as detailed above. Net Cash Used in Operating Activities for the second quarter of 2017 decreased by $0.6 million or 6% compared to the first quarter of 2017.

Net Cash Used in Investing Activities for the second quarter of 2017 was $4.9 million, an increase of $1.9 million or 67% compared to the second quarter of 2016. Net Cash Used in Investing Activities for the second quarter of 2017 decreased by $13.7 million compared to the first quarter of 2017. The decrease was mainly due to change in short-term investments.

Cash Balance6 as of June 30, 2017, was $51 million, a decrease of $15 million, compared to $66 million as of December 31, 2016, and a decrease of $10 million compared to March 31, 2017. The decrease was a result of the ongoing operations, mainly related to research and development activities and the establishment of the U.S. commercial operations.

Micha Ben Chorin, RedHill’s CFO, said: "We are pleased with the important milestones achieved during the second quarter, including positive top-line results from the Phase III GUARD study with BEKINDA 24 mg for acute gastroenteritis, initiation of the confirmatory Phase III study with TALICIA for the treatment of H. pylori infection, and the initiation of promotional activities in the U.S. by our GI-focused sales force with Donnatal and EnteraGam, which generated encouraging initial net revenues of approximately $0.5 million in the second half of June alone. Our cash position of $51 million at the end of the second quarter should allow us to continue to execute our strategic plans, diligently advance our late-stage clinical programs and pursue the acquisition of additional commercial GI products in the U.S."

On July 25, 2017 Celgene Corporation (NASDAQ:CELG) reported that it has reached a civil settlement with Relator Brown, the Department of Justice, 28 States, the District of Columbia, and the City of Chicago to resolve the previously disclosed False Claims Act litigation pending in the United States District Court for the Central District of California (Press release, Celgene, JUL 25, 2017, View Source [SID1234519881]). The litigation related primarily to allegations that Celgene promoted Thalomid (thalidomide) for off-label uses before its 2006 FDA approval for newly diagnosed multiple myeloma. The Department of Justice, the States, the District of Columbia, and the City of Chicago declined to intervene in the litigation.

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Under the settlement, Celgene will pay a total of $280 million to the United States, 28 States, the District of Columbia, and the City of Chicago to resolve the litigation. This final settlement includes the resolution of all allegations the Relator made with respect to Thalomid and Revlimid (lenalidomide). Before the parties reached a settlement, the Court dismissed a significant part of the case on a motion for summary judgment, including allegations that Celgene illegally paid doctors to induce them to promote and/or prescribe Thalomid and Revlimid. Celgene is not required to enter into a Corporate Integrity Agreement as part of the settlement.

Celgene has denied any wrongdoing in this matter, but is settling to avoid the uncertainty, distraction, and expense of protracted litigation. Celgene contends, and has contended throughout the litigation, that Thalomid and Revlimid are medical breakthrough medicines that have benefitted patients with serious illnesses; that physicians prescribed these medicines based on their independent medical judgment; and that Celgene’s relationships with physicians have been appropriate, and have helped to advance patient care and science.