On November 15, 2018 Seattle Genetics, Inc. (Nasdaq:SGEN) reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to ADCETRIS (brentuximab vedotin) for previously untreated systemic anaplastic large cell lymphoma or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with CHP (cyclophosphamide, doxorubicin, and prednisone) (Press release, Seattle Genetics, NOV 15, 2018, View Source [SID1234531359]). The positive topline results of the phase 3 ECHELON-2 clinical trial were announced in October 2018, followed by the submission of a supplemental Biologics License Application (BLA) to the FDA in November 2018. Additional data will be presented at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, December 1-4, 2018 in San Diego, Calif. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on the surface of several types of PTCL. ADCETRIS is currently not approved for the frontline treatment of PTCL.

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The FDA’s Breakthrough Therapy Designation is intended to expedite the development and review of promising drug candidates for serious or life-threatening conditions. It is based upon clinical evidence of substantial improvement over existing therapies on one or more clinically significant endpoints.

"Data from the ECHELON-2 phase 3 trial of ADCETRIS in combination with chemotherapy showed superior progression-free survival and overall survival versus the standard of care chemotherapy regimen, CHOP, in the treatment of frontline CD30-expressing peripheral T-cell lymphomas," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "This is the third Breakthrough Therapy Designation for ADCETRIS and supports our goal to make this therapy available to patients with newly diagnosed peripheral T-cell lymphomas as soon as possible. We look forward to presenting the data from our phase 3 ECHELON-2 trial at the upcoming ASH (Free ASH Whitepaper) Annual Meeting."

This Breakthrough Therapy Designation was based on data from the phase 3 ECHELON-2 clinical trial evaluating the combination of ADCETRIS plus CHP versus the control arm, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), in previously untreated CD30-expressing PTCL. The ECHELON-2 study met its primary endpoint demonstrating a statistically significant improvement in progression-free survival (PFS) of ADCETRIS in combination with CHP versus CHOP as assessed by an Independent Review Facility (IRF; hazard ratio=0.71; p-value=0.0110). The ADCETRIS plus CHP arm also demonstrated superior overall survival (OS), a key secondary endpoint, compared to CHOP (hazard ratio=0.66; p-value=0.0244). All other key secondary endpoints, including PFS in patients with systemic anaplastic large cell lymphoma (sALCL), complete remission rate and objective response rate were statistically significant in favor of the ADCETRIS plus CHP arm. The safety profile of ADCETRIS plus CHP in the ECHELON-2 trial was comparable to CHOP and consistent with the established safety profile of ADCETRIS in combination with chemotherapy.

ECHELON-2 Phase 3 Clinical Trial Design

The randomized, double-blind, placebo-controlled phase 3 trial is investigating ADCETRIS plus CHP (cyclophosphamide, doxorubicin, prednisone) versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) as frontline therapy in patients with CD30-expressing peripheral T-cell lymphoma, also known as mature T-cell lymphoma. The primary endpoint is progression-free survival (PFS) per Independent Review Facility assessment, with events defined as progression, death, or receipt of chemotherapy for residual or progressive disease. Secondary endpoints include PFS in patients with systemic anaplastic large cell lymphoma (sALCL), complete remission rate, overall survival and objective response rate, in addition to safety. The multi-center trial was conducted at sites across North America, Europe and Asia and was designed to enroll 450 patients, approximately 75 percent of whom were to be diagnosed with sALCL. The ECHELON-2 trial is being conducted under a Special Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration (FDA) and the trial also received European Medicines Agency (EMA) scientific advice.

Please see Important Safety Information, including Boxed Warning, at the end of this press release.

About T-Cell Lymphomas

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. There are more than 60 subtypes of non-Hodgkin lymphomas which are broadly divided into two major groups: B-cell lymphomas, which develop from abnormal B-lymphocytes, and T-cell lymphomas, which develop from abnormal T-lymphocytes. There are many different forms of T-cell lymphomas, some of which are extremely rare. T-cell lymphomas can be aggressive (fast-growing) or indolent (slow-growing). PTCL accounts for approximately 10 percent of non-Hodgkin lymphoma cases in the U.S. and Europe and may be as high as 24 percent in parts of Asia.

About ADCETRIS (brentuximab vedotin)

ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include the recently completed phase 3 ECHELON-2 trial in frontline peripheral T-cell lymphomas (also known as mature T-cell lymphoma), the completed phase 3 ECHELON-1 trial in previously untreated Hodgkin lymphoma, the completed phase 3 ALCANZA trial in cutaneous T-cell lymphoma, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS injection for intravenous infusion has received FDA approval for five indications in adult patients with: (1) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with chemotherapy, (2) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (3) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (4) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (5) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.

ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, and (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

ADCETRIS has received marketing authorization by regulatory authorities in 72 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

On November 15, 2018 PsiOxus Therapeutics, Ltd. (PsiOxus) and the Parker Institute for Cancer Immunotherapy (Parker Institute) reported a research project to investigate the use of PsiOxus’ virus-based gene therapy for treating solid tumors that have been historically resistant to immunotherapy (Press release, PsiOxus Therapeutics, NOV 15, 2018, View Source [SID1234531403]).

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This pre-clinical immuno-oncology research will utilize PsiOxus’ proprietary T-SIGn platform. The platform uses the enadenotucirev oncolytic virus as a vector to deliver combinations of therapeutic transgenes to carcinomas to fight cancer.

In effect, the T-SIGn viruses work by turning tumor cells into "drug factories" to express gene therapy products, such as cytokines or antibodies, designed to engage the immune system to attack cancer cells.

The viruses first selectively infect and replicate only in tumor cells. The tumor cells then express the encoded genes, producing biologic therapies to alter the tumor microenvironment. Changing the tumor microenvironment is believed to enhance the activation of cancer-fighting immune cells so they can eradicate the tumor.

Working together, PsiOxus and the Parker Institute aim to build and test viruses carrying different combinations of genes.

"One of the challenges in treating solid tumors with immunotherapy is the tumor microenvironment, which is very suppressive and effectively prevents the immune system from attacking the tumor," said Fred Ramsdell, Ph.D., vice president of research at the Parker Institute. "What is promising about the PsiOxus approach is its potential to overcome this suppression using a novel virus platform to deliver gene therapy."

Unlike other oncolytic viruses that require direct injections to the tumor, which can be costly and complicated to administer, PsiOxus’ platform can be delivered to patients intravenously.

"Given the potential of PsiOxus’ IV-delivered cancer gene therapy platform, establishing strategic relationships with world leaders in immuno-oncology will accelerate our ability to bring gene therapy treatment to cancer patients," said Brian Champion, Ph.D., Chief Scientific Officer of PsiOxus. "The Parker Institute is a leader in building strategic relationships between leading immuno-oncology academic and industry partners. We are thrilled to collaborate with the Parker Institute to jointly accelerate research on innovative cancer immuno-oncology therapy."

On November 15, 2019 GT Biopharma, Inc. (OTCQB: GTBP and Euronext Paris GTBP.PA) ("GT Biopharma" or the "Company"), an immuno-oncology biotechnology company focused on innovative treatments based on the Company’s proprietary NK-engager and Bispecific Antibody Drug Conjugate platforms, reported its financial results for the third quarter ended September 30, 2018 (Press release, GT Biopharma , NOV 15, 2018, View Source [SID1234539520]).

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The Company also provided an update on its corporate progress, clinical status and anticipated milestones for its pipeline of immuno-oncology products based off the Company’s proprietary Tri-specific Killer Engager (TriKE), Tetra-specific Killer Engager (TetraKE) and bi-specific Antibody Drug Conjugate (ADC) technology platforms.

Recent Corporate Highlights:

Received FDA clearance to commence first-in-human Phase 1 study of first-in-class TriKE, GTB-3550 (OXS-3550), for the treatment of acute myelogenous leukemia, myelodysplatic syndrome and mastocytosis.

Announced positive preclinical data for two next generation TriKEs in ovarian and head and neck cancers. The studies were conducted by Dr. Daniel Vallera, Director, Section of Molecular Cancer Therapeutics and Dr. Martin Felices, Co-Director of the Translational Therapy Laboratory at the Masonic Cancer Center, University of Minnesota.

Announced agreement with major pharmaceutical company and initiated preclinical combination trial of GTB-1550 (OXS-1550) and multi-billion dollar oncology drug for testing in several hematologic malignancies.

Bolstered leadership team with appointments of Dr. Raymond W. Urbanski M.D., Ph.D. as CEO and Chairman of the Board (formerly Chief Medical Officer of the Company); well-respected industry veteran, Dr. John N. Bonfiglio as a new independent Board Member and David Cardino, CPA, as VP, Finance.
"We have made significant progress in building a solid foundation for the Company in what we believe is an important transitional phase for GT Biopharma. The additions and changes to the leadership team and execution of key preclinical, clinical and regulatory milestones are a testament to this progress," commented Raymond Urbanski, M.D., Ph.D., Chief Executive Officer of GT Biopharma. "However, as we navigate through this phase, we certainly face challenges, including ensuring we are properly funded and have the right team in place to propel the Company to our next phase of growth. Successfully completing a financing and bolstering our management team and Board in the near term remains a priority. I, along with our Board, believe GT Biopharma has a first-in-class platform technology and the potential to provide revolutionary advancements in the treatment of various cancers where there remains significant unmet need. We are committed to securing the necessary capital to continue to aggressively execute on our strategy and advance our development programs to drive significant shareholder value. I believe we are taking the necessary steps to position GT Biopharma for a transformational 2019."

Clinical Program Updates

The Company’s TriKE product candidates are single-chain, tri-specific scFv recombinant fusion proteins composed of the variable regions of the heavy and light chains (or heavy chain only) of anti-CD16 antibodies, wild-type or a modified form of IL-15 and the variable regions of the heavy and light chains of an antibody designed to precisely target a specific tumor antigen. GT Biopharma utilizes the NK stimulating cytokine human IL-15 as a crosslinker between the two scFvs which is designed to provide a self-sustaining signal leading to the proliferation and activation of NK cells thus enhancing their ability to kill cancer cells mediated by antibody-dependent cell-mediated cytotoxicity (ADCC).

The Company’s TetraKE product candidates are single-chain fusion proteins composed of human single-domain anti-CD16 antibody, wild-type IL-15 and the variable regions of the heavy and light chains of two antibodies that are designed to target two specific tumor antigens expressed on specific types of cancer cells.

GT Biopharma’s TriKEs and TetraKEs are designed to act by binding to a patient’s NK cells and a specific tumor antigen enabling an immune synapse between the now IL-15-enhanced NK cell and the targeted cancer cell. The formation of an immune synapse can induce NK cell activation which can lead to the death of the cancer cell. The Company believes the self-sustaining signal caused by its IL-15 cross-linker may enable prolonged and enhanced proliferation and activation of NK cells similar to the increased proliferation of T-cells caused by 41BB-L or CD28 intracellular domains in CAR-T therapy but without the need to enhance the patient’s NK cells ex vivo.

GTB-1550 (OXS-1550): Most Advanced Bi-specific ADC Candidate

The Company’s most advanced bi-specific ADC in development, GTB-1550, targets CD19+ and/or CD22+ hematological malignancies and is currently in the Phase 2 component of a Phase 1/2 Non-Hodgkin’s Lymphoma (NHL)/Acute Lymphocytic Leukemia (ALL) trial which is an open-label, investigator-led study.

GTB-1550 targets cancer cells expressing the CD19 receptor or CD22 receptor or both receptors. When GTB-1550 binds to cancer cells, the cancer cells internalize GTB-1550, and are killed due to the action of drug’s cytotoxic diphtheria toxin payload. GTB-1550 has demonstrated success in a Phase 1 human clinical trial in patients with relapsed/refractory B-cell lymphoma or leukemia.

The Company recently assembled a Bi-Specific ADC Advisory Board to collaboratively assess and interpret the GTB-1550 pre-clinical and clinical data, including an interim review of the Phase 1/2 study. Eighteen patients have been enrolled to date, including 12 NHL and six ALL patients. At the time of the interim review, 13 patients met the evaluation criteria, including nine NHL and four ALL patients. More than 50% of patients (seven of 13) exhibited a clinical benefit, defined as stable disease, partial remission or complete remission at Day 29. Of the seven patients, one demonstrated a complete remission (CR), one demonstrated a partial remission (PR) and five demonstrated stable disease (SD).

The efficacy signal was more prominent in ALL patients with 75% (three of four) exhibiting clinical benefit including one CR, one PR and one SD. In the NHL population, four of nine patients exhibited SD. Adverse events were mostly grade 1 and 2 and reversible. One patient had a grade 4 low platelet count, two patients had a grade 3 increase in liver function tests, or LFTs, and one patient had a grade 3 capillary leak. The Company currently expects final data for this trial to be available in the first quarter of 2019.

This work is being conducted by and under the guidance of Dr. Veronika Bachanova, Associate Professor of Medicine, Division of Hematology, Oncology and Transplantation at the University of Minnesota.

GTB-3550 (OXS-3550): TriKE product candidate

GTB-3550 is the Company’s first Tri-specific Killer Engager (TriKE) product candidate being initially developed for the treatment acute myelogenous leukemia (AML). GTB-3550 is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies and a modified form of IL-15. When the NK stimulating cytokine human IL-15 is used as a crosslinker between the two scFvs, it provides a self-sustaining signal that activates NK cells and enhances their ability to kill.

GT Biopharma recently announced that its Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) is now open and it is authorized to initiate a first-in-human Phase 1 study with GTB-3550, its first-in-class TriKE, for the treatment of AML, myelodysplatic syndrome (MDS) and mastocytosis. The study will be led by Principal Investigator, Sarah A. Cooley, MD, MS, Associate Professor, Division of Hematology, Oncology and Transplantation at Masonic Cancer Center, University of Minnesota.

This single center, first-in-human Phase 1 clinical trial of GTB-3550 will enroll up to 60 subjects with CD33-expressing refractory/relapsed AML, high-risk MDS, or advanced systemic mastocytosis. Subjects will receive a single course of GTB-3550 given as 3 weekly treatment blocks. Each block consists of four consecutive 24-hour continuous infusions of GTB-3550 followed by a 72-hour break after Block #1 and #2. Disease response will be assessed by bone marrow biopsy performed between Day 21 and Day 42 after the start of the 1st infusion. Follow-up for response and survival continues through 6 months from treatment start. The primary objective from the Phase 1 dose finding portion of the study will be to identify the maximum tolerated dose (MTD) of GTB-3550 defined as the dose level that most closely corresponds to a dose limiting toxicity rate (DLT) of 20%. The primary objective from the Phase 2 extended portion of the study will be the potential efficacy of GTB-3550, measured using rates of complete and partial remission. Subjects experiencing clinical benefit and no unacceptable side effects may be considered for a 2nd course of GTB-3550 on a compassionate basis.

The Company believes that GTB-3550 could serve as a relatively safe, cost-effective, and easy-to-use therapy for refractory/relapsed AML, high-risk MDS and advanced systemic mastocytosis and could also be combined with chemotherapy and/or other agents as frontline therapy thus targeting a much larger patient population.

GT Biopharma’s initial and ongoing work is being conducted in collaboration with the Masonic Cancer Center at the University of Minnesota under research agreements led by Dr. Jeffrey Miller, the Deputy Director and Dr. Daniel Vallera, Director, Section of Molecular Cancer Therapeutics.

GT Biopharma has an exclusive worldwide license agreement with the University of Minnesota to further develop and commercialize cancer therapies using proprietary TriKE technology developed by researchers at the university to target NK cells to cancer.

Upcoming Milestones Expected to Drive Value

Initiate Phase 1 first-in-human clinical trial of GTB-3550 for the treatment of Relapse/Refractory AML, High Risk MDS, and Advanced Systemic Mastocytosis in the first half of 2019;
Announce topline results from Phase 2a trial of GTB-1550 in Q1 2019;
Conduct end of Phase 2a (EOP2a) meeting for GTB-1550 with U.S. FDA in the first half of 2019;
Advance ongoing GTB-C3550 IND-enabling studies & TetraKE pre-clinical program to target the larger solid tumor population and are working towards beginning clinical trials in 2019;
Bolster executive management team and board with key expertise to continue to transform the Company;
Participate in key scientific conferences;
Make progress in advancing potential corporate and business development opportunities; and
Uplist to a National Exchange.
Summary of Financial Results for Third Quarter 2018

For the quarter ended September 30, 2018, the Company reported a net loss of approximately $235,783,000 or a net loss per diluted share of $4.70, compared to a net loss of $130,625,000 or a net loss per diluted share of $8.15 for the same quarter 2017. For the nine months ended September 30, 2018, GT Biopharma reported a net loss of approximately $254,955,000 or a net loss per diluted share of $5.09, compared to $138,146,000 or a net loss per diluted share of $24.54 for the same period 2017.

At September 30, 2018, the Company has an accumulated deficit of $524,453,000 and cash of $1,232,000.

On November 15, 2018 Akari Therapeutics, Plc (NASDAQ:AKTX), a biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory diseases where complement and or leukotriene systems are implicated, reported its financial results for the third quarter ended September 30, 2018 (Press release, Akari Therapeutics, NOV 15, 2018, View Source [SID1234531344]).

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"We are focused on moving our four priority clinical programs forward and expect initial data from our trials in patients with bullous pemphigoid (BP) and atopic keratoconjunctivitis (AKC) in the first quarter of 2019," commented Clive Richardson, Interim Chief Executive Officer of Akari Therapeutics.

Clinical development highlights and upcoming milestones

Coversin clinical trials focused on orphan diseases mediated by both the complement and leukotriene pathways with initial data readouts expected in the first quarter 2019:
Phase II trial in patients with BP, a severe blistering skin disease
Phase I/II trial in patients with AKC, a sight-threatening surface of the eye condition
Coversin clinical trials in orphan diseases in which complement dysregulation is the primary disease driver:
Two trials open in PNH: a Phase III trial in naïve patients and a Phase II trial in patients who are resistant to eculizumab
An open Phase II trial in atypical hemolytic syndrome (aHUS), a severe thrombotic microangiopathy
Ongoing named patient program in pediatric patients with thrombotic microangiopathy (TMA) post bone marrow transplant
Long-term safety study for Coversin
Total cumulative number of patient-years on Coversin treatment approximately 15 years
All patients in the long term study have now been treated for more than 15 months and the first patient has now been treated for 34 months
No drug related serious adverse events and no neutralizing antibodies reported to date
Six PNH patients were transfusion dependent prior to treatment with Coversin, of which four in the long-term study are now transfusion independent; two remain on transfusion.
Third Quarter 2018 Financial Results

Research and development (R&D) expenses in the third quarter of 2018 were $3.3 million, as compared to $6.4 million in the same quarter the prior year. The decrease was due primarily to lower manufacturing costs for Coversin as the Company had previously manufactured clinical trial material for supply through 2019, partially offset by higher clinical trial activity.
General and administrative (G&A) expenses in the third quarter of 2018 were $2.4 million, as compared to $2.2 million in the same quarter last year. This increase was due primarily to higher professional fees.
Operating expenses were $3.0 million in the third quarter of 2018. Excluding a $2.7 million one-time litigation settlement gain, operating expenses were $5.7 million in the third quarter of 2018, as compared to $8.5 million in the same quarter the prior year. This decrease is primarily due to lower R&D expenses.
Total other expense for the third quarter of 2018 was $0.6 million, as compared to $1.8 million in the same quarter the prior year. This change was primarily attributed to a $0.7 million loss in fair value of the stock option liabilities in the third quarter of 2018, compared to a $1.7 million loss in the third quarter of 2017.
Net loss for the third quarter of 2018 was $3.6 million, compared to a net loss of $10.4 million for the same period in 2017. This year over year decrease in net loss was due primarily to the aforementioned $2.7 million litigation settlement gain, lower R&D expenses and change in fair value of the stock option and warrant liabilities, which were lower in the third quarter of 2018 compared to the prior year period.
As of September 30, 2018, the Company had cash of $10.1 million, as compared to cash of $28.1 million as of December 31, 2017.
In addition, on September 26, 2018, the Company entered into a securities purchase agreement (the "Purchase Agreement") with Aspire Capital Fund, LLC ("Aspire Capital"), which provides that, upon the terms, Aspire Capital is committed to purchase up to an aggregate of $20.0 million of the Company’s ADSs over the 30-month term of the Purchase Agreement. In consideration for entering into the Purchase Agreement, concurrently with the execution of the Purchase Agreement, the Company issued 30,000,000 ordinary shares to Aspire Capital and sold to Aspire Capital 25,000,000 ordinary shares for $0.02 per share (equivalent to $2.00 per ADS and $500,000).

On November 15, 2018 Ipsen (Euronext: IPN; ADR: IPSEY) reported that the European Commission (EC) has approved Cabometyx (cabozantinib) 20, 40, 60 mg as a monotherapy for hepatocellular carcinoma (HCC) in adults who have previously been treated with sorafenib (Press release, Ipsen, NOV 15, 2018, View Source [SID1234531360]). This approval allows for the marketing of Cabometyx (cabozantinib) in this indication in all 28 member states of the European Union, Norway and Iceland.

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"Today’s EC approval for the use of Cabometyx provides a much needed new option for HCC patients. Until now, physicians in Europe had only one approved therapy for the 2nd line treatment of this aggressive and difficult-to-treat cancer.1,2 We are proud to offer Cabometyx as an innovative treatment that has been shown to extend survival in previously treated patients with HCC," said Harout Semerjian, Chief Commercial Officer, Ipsen. "This new indication reinforces Ipsen’s commitment to improve patients’ lives through the expansion of the clinical benefit of Cabometyx in the treatment of solid tumors."

Philippe Merle, M.D., Ph.D., Hepatology and Gastroenterology specialist at La Croix-Rousse Hospital, Lyon, stated: "Patients with HCC in Europe can now benefit from a treatment that has, through the CELESTIAL trial, proven effective in prolonging life and delaying disease progression. This is a very encouraging development for liver cancer patients, and provides physicians with a new therapeutic option for this complex disease."

The EC approval is based on the results of the global placebo-controlled CELESTIAL phase 3 pivotal trial which met its primary endpoint of overall survival (OS), with cabozantinib providing a statistically significant and clinically meaningful improvement in OS compared with placebo in patients with advanced HCC who have been previously treated with sorafenib.3 In July 2018, CELESTIAL phase 3 pivotal trial results were published in the New England Journal of Medicine.3

The EC has also approved Cabometyx for the treatment of advanced renal cell carcinoma (aRCC) both in treatment-naïve adults with intermediate or poor risk (May 2018) and in adults following prior vascular endothelial growth factor (VEGF)-targeted therapy (September 2016).

The detailed recommendations for the use of this product are described in the Summary of Product Characteristics (SmPC), available here.

About CELESTIAL

CELESTIAL is a randomized, double-blind, placebo-controlled global phase 3 study of cabozantinib versus placebo in patients with advanced HCC who have been previously treated with sorafenib. The study was conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who previously received sorafenib and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017, and 773 patients were ultimately randomized. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region (Asia versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms.

The primary endpoint for the trial is OS, and secondary endpoints include objective response rate (ORR) and progression-free survival (PFS). Exploratory endpoints include patient-reported outcomes, biomarkers and safety.

Based on available clinical trial data from various published trials conducted in the second-line setting of advanced HCC, the CELESTIAL trial statistics for the primary endpoint of OS assumed a median OS of 8.2 months for the placebo arm. A total of 621 events provide the study with 90 percent power to detect a 32 percent increase in median OS (HR = 0.76) at the final analysis. Two interim analyses were planned and conducted at 50 percent and 75 percent of the planned 621 events. The independent data monitoring committee for the study recommended that the trial should be stopped for efficacy following review of the second planned interim analysis. CELESTIAL trial met its primary endpoint, with cabozantinib providing a statistically significant and clinically meaningful improvement in OS compared to placebo in patients with advanced HCC. The safety data in the study were consistent with the established profile of cabozantinib.

About Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma is the most common form of liver cancer in adults.4 The disease originates in cells called hepatocytes found in the liver. With approximately 800’000 new cases diagnosed each year, HCC is the sixth most common cancer and the second-leading cause of cancer deaths worldwide.5,6 According to the GLOBOCAN data, it is estimated that across the European Union (EU-28) nearly 60’000 new patients will be diagnosed with liver cancer in 2020.7 Without treatment, patients with the disease in advanced stage usually survive between 4 and 8 months.8

About Cabometyx (cabozantinib)

Cabometyx is an oral small molecule inhibitor of tyrosine kinase receptors, including VEGFR, MET, AXL and RET. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.

In February of 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan. This agreement was amended in December of 2016 to include commercialization rights for Ipsen in Canada.

Cabometyx tablets are approved in the United States for the treatment of patients with advanced RCC. On September 9, 2016, the European Commission approved Cabometyx tablets for the treatment of advanced RCC in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy in the European Union, Norway and Iceland. Cabometyx is also approved in Australia, Brazil, Canada, Hong Kong, South Korea, Switzerland, Taiwan and Ukraine. Cabometyx is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.

On May 17, 2018, Ipsen announced that the European Commission approved Cabometyx for the first-line treatment of adults with intermediate- or poor- risk advanced renal cell carcinoma in the European Union, Norway and Iceland.

On November 15, 2018, Ipsen announced that the European Commission approved Cabometyx for the second-line treatment of hepatocellular carcinoma in adults who have previously been treated with sorafenib in the European Union, Norway and Iceland.