On June 20, 2017 Seattle Genetics, Inc. (Nasdaq: SGEN) reported that it has submitted a supplemental Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) based on data from the phase 3 ALCANZA trial and two phase 2 investigator-sponsored trials of ADCETRIS (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL) (Press release, Seattle Genetics, JUN 20, 2017, View Source [SID1234519618]). ADCETRIS is currently not approved for the treatment of CTCL. Schedule your 30 min Free 1stOncology Demo! "The submission of the supplemental BLA requesting label expansion for ADCETRIS as a treatment in CTCL patients who require systemic therapy is an important milestone. CTCL is an incurable and disfiguring disease in need of new therapeutic options, particularly those that achieve durable responses," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development of Seattle Genetics. "Results from the phase 3 ALCANZA trial demonstrated that CTCL patients treated with ADCETRIS had superior outcomes across all primary and secondary endpoints compared to patients in the control arm who were treated with either methotrexate or bexarotene standard of care agents. In addition to the ALCANZA results, data from two investigator-sponsored trials also support ADCETRIS use in this disease setting. We believe these data are clinically meaningful and support a label expansion for ADCETRIS in CTCL, which would be the fourth indication for this program."
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In November 2016, based on preliminary analysis of ALCANZA, the FDA granted ADCETRIS Breakthrough Therapy Designation (BTD) for the treatment of patients with CD30-expressing mycosis fungoides and primary cutaneous anaplastic large cell lymphoma who require systemic therapy and have received one prior systemic therapy. These represent the most common subtypes of CTCL. Based on discussions with the FDA following the BTD, additional data from investigator-sponsored phase 2 trials have been incorporated into the supplemental BLA to support the potential for a broader label in CTCL.
The supplemental BLA is primarily based on positive results from a phase 3 trial called ALCANZA that were presented at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2016 and published in the Lancet in June 2017. Results from the ALCANZA trial in 128 CTCL patients requiring systemic therapy included:
The trial achieved its primary endpoint with the ADCETRIS treatment arm demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4) versus the control arm as assessed by an independent review facility. ORR4, as assessed by Global Response Score, was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm (p-value <0.0001).
Key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in the burden of symptoms during treatment (Skindex-29), were all highly statistically significant in favor of the ADCETRIS arm.
The safety profile associated with ADCETRIS from the ALCANZA trial was generally consistent with the existing prescribing information. The most common adverse events of any grade include: peripheral neuropathy, nausea, diarrhea, fatigue, vomiting, alopecia, pruritis, pyrexia, decreased appetite and hypertriglyceridemia.
About CTCL
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. Cutaneous lymphomas are a category of non-Hodgkin lymphoma that primarily involve the skin. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. Progression from limited skin involvement may be accompanied by skin tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs.
The standard treatment for systemically pretreated CTCL includes skin-directed therapies, radiation and systemic therapies. The systemic therapies currently approved for treatment have demonstrated 30 to 45 percent objective response rates, with low complete response rates.
About ADCETRIS
ADCETRIS is being evaluated broadly in more than 70 ongoing clinical trials, including three Phase 3 studies, the ongoing ECHELON-1 trial in frontline classical Hodgkin lymphoma and the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, as well as the completed ALCANZA trial in cutaneous T-cell lymphoma, from which data were submitted in a supplemental BLA.
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-positive tumor cells.
ADCETRIS for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL.
ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. The European Commission extended the current conditional marketing authorization of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT.
ADCETRIS has received marketing authorization by regulatory authorities in 67 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information 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.
Month: June 2017
AVEO Oncology Announces Pivotal Phase 3 TIVO-3 Study of Tivozanib in Renal Cell Carcinoma Reaches Enrollment Target
On June 20, 2017 AVEO Oncology (NASDAQ: AVEO) reported that the Company’s pivotal TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC) has reached its enrollment target of 322 patients, more than two months ahead of the Company’s initial guidance (Press release, AVEO, JUN 20, 2017, View Source [SID1234519616]). Tivozanib, the Company’s lead program, is a potent, selective, long half-life inhibitor of all three vascular endothelial growth factor (VEGF) receptors. A pre-planned futility analysis of the TIVO-3 trial is expected around midyear 2017, with topline data expected in the first quarter of 2018. The trial, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of RCC, is designed to support regulatory approval of tivozanib in the U.S. as a first and third line treatment for RCC. Schedule your 30 min Free 1stOncology Demo! "Reaching our enrollment goal for the TIVO-3 trial is a meaningful milestone for AVEO, which we believe reflects the support of many individuals within the Company, our medical partners in the oncology community and the patients we serve," said Michael Bailey, president and chief executive officer of AVEO. "As previously noted, based on a recommendation by the Safety Monitoring Committee, the study will continue enrolling additional patients for the next few weeks to replace early dropouts. We look forward to several key upcoming potential inflection points in the tivozanib program, including a European regulatory decision and ongoing enrollment in the TiNivo study, culminating in the readout of the TIVO-3 trial, expected in the first quarter of 2018."
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The TIVO-3 trial is enrolling patients with recurrent RCC who have failed at least two prior regimens, including VEGFR-TKI therapy (other than sorafenib). Eligible patients may also have received checkpoint inhibitor therapy in earlier lines of treatment. Patients will be randomized 1:1 to receive either tivozanib or sorafenib, with no crossover between arms. The primary endpoint of the study is progression free survival. Secondary endpoints include overall survival, overall response rate, and safety and tolerability.
About Tivozanib
Tivozanib is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI). It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications. Tivozanib has been investigated in several tumors types, including renal cell, colorectal and breast cancers.
OncoSynergy and Infuseon Therapeutics Partner to Combat Glioblastoma
On June 20, 2017 Infuseon Therapeutics and OncoSynergy have entered into a strategic alliance to test an investigational glioblastoma therapeutic, OS2966, in combination with a novel delivery device, the Cleveland Multiport CatheterTM (Press release, OncoSynergy, JUN 20, 2017, View Source [SID1234519626]). Glioblastoma is the most common and malignant primary brain tumor. Despite a median survival of merely 12 months, there have been only four FDA approved therapies and no improvement in overall survival in nearly three decades. This unmet need is driven in part by the inability of most chemotherapies and particularly biologics to penetrate the blood-brain-barrier.
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Infuseon Therapeutics’ unique therapy delivery device, the Cleveland Multiport CatheterTM (CMC), a multiport convection-enhanced delivery catheter, was designed by neurosurgeon Michael Vogelbaum, MD, PhD, from Cleveland Clinic’s Brain Tumor and NeuroOncology Center, to more effectively deliver life-saving drugs to patients at the site of their disease. The reliability of the CMC as a loco-regional delivery device has been validated in pilot clinical trials involving delivery of a chemotherapy along with an MRI visible tracer in patients with recurrent high grade gliomas.
OncoSynergy is a UCSF spinout headquartered at Johnson & Johnson Innovation, JLABS (JLABS) in South San Francisco. JLABS @ SSF is a 30,000 square-foot life science innovation incubator, located in South San Francisco. The labs provide a flexible environment for start-up companies pursuing new technologies and research platforms to advance medical care. Through a “no strings attached” model, Johnson & Johnson Innovation does not take an equity stake in the companies occupying JLABS and the companies are free to develop products – either on their own, or by initiating a separate external partnership with Johnson & Johnson Innovation or any other company. OncoSynergy’s first-in-class humanized and de-immunized monoclonal pan-CD29 antibody, OS2966, has demonstrated dramatic efficacy in multiple models of highly aggressive and metastatic solid cancers. Based on these data, the FDA has granted two Orphan Drug Designations for OS2966 including in the treatment of glioblastoma.
“We are pleased to join forces with Infuseon Therapeutics to tackle the complex biology of glioblastoma,” commented Anne-Marie Carbonell, MD, Vice President of Clinical Development at OncoSynergy. “The innovative combination of OS2966 and the CMC device seeks to address a huge unmet need and potentially change the way we treat patients suffering from malignant brain tumors.”
The collaboration aims to establish proof of concept that OS2966 can be successfully delivered directly to the brain with the CMC device as an impetus for a Phase I trial for the treatment of glioblastoma.
“Infuseon’s Cleveland Multiport Catheter was designed specifically to deliver therapeutics directly to the site of disease,” said Michael Vogelbaum, MD, PhD, co-Founder and Chief Medical Officer of Infuseon Therapeutics. “We are excited to pursue a potentially novel therapeutic approach to this difficult disease.”
About Infuseon Therapeutics – Infuseon Therapeutics was founded in 2012 by Cleveland Clinic for the purpose of developing its patented unique therapeutic delivery device, the Cleveland Multiport CatheterTM (CMC). Infuseon has collaborated with Parker-Hannifin Corporation, a global leader in motion and control technologies to enhance the medical design, development, and manufacturing expertise of the company. As an inventor of the multiport catheter, Dr. Vogelbaum is entitled to a portion of any commercialization revenues Cleveland Clinic receives from Infuseon. To learn more visit www.infuseontherapeutics.com
Media contact: Neema Mayhugh, PhD [email protected] (216) 312-9165
About OncoSynergy – Oncosynergy is a UCSF spinout with primary operations in JLABS @ SSF, California. The company was founded in 2011 to address the complexity of cancer for more durable patient outcomes through the development of a new class of oncology therapeutics, called Resistance Mechanism Inhibitors (RMIs). RMIs uniquely inhibit multiple Cancer Hallmarks simultaneously. The lead RMI drug candidate, OS2966, is on track for Phase I clinical trials in 2018. To learn more visit www.oncosynergy.com
Media Contact: Shawn Carbonell, MD, PhD, [email protected] +1 (415) 666-2391
20-F – Annual and transition report of foreign private issuers [Sections 13 or 15(d)]
On December 18, 2017 Pharmaceuticals, Inc. (NASDAQ: REGN) and ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company, reported a clinical collaboration to advance ISA101, an immunotherapy targeting human papillomavirus type 16 (HPV16)-induced cancer, in combination with cemiplimab (REGN2810), a PD-1 (programmed cell death protein 1) antibody (Press release, Regeneron, DEC 18, 2017, View Source [SID1234522678]). Regeneron and ISA will jointly fund and conduct clinical trials of the combination treatment in cervical cancer and head-and-neck cancer.
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Expression of HPV oncoproteins contributes to the development of cervical and head-and-neck cancers, and approximately 55 percent of cervical cancers and over 60 percent of head-and-neck cancers are HPV16 positive.1
Regeneron and ISA will share clinical trial costs and exchange product supply. In addition, Regeneron will provide an upfront payment and an equity investment in exchange for an option to an exclusive, global license for ISA101. If Regeneron exercises its option to commercialize ISA101, there is potential for various milestone payments and tiered royalty payments to ISA contingent on regulatory approvals, sales and additional indications. Further financial details were not disclosed.
"Regeneron continues to expand and advance our immuno-oncology program by studying multiple combination therapies in order to fully explore the scientific possibilities in this relatively new field," said Israel Lowy, M.D., Ph.D., Vice President Clinical Sciences, Head of Translational Science and Oncology at Regeneron. "Early clinical results with ISA101 in HPV16-positive indications have been promising, and we’re eager to investigate the impact of adding cemiplimab with the goal of further enabling the body’s immune system to attack the cancer."
"This collaboration with Regeneron is a strong validation of our proprietary SLP (Synthetic Long Peptides) platform and know-how," added Ronald Loggers, Chief Executive Officer of ISA Pharmaceuticals. "We are proud to work with Regeneron, a science- and technology-driven biotechnology company, and aim to further strengthen our pioneering role in the development of innovative treatment options for oncology indications with a high unmet medical need."
Cemiplimab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement for immuno-oncology therapeutics, and was developed using Regeneron’s proprietary VelocImmune technology that yields optimized fully-human antibodies. Cemiplimab is currently being studied as a monotherapy in multiple cancers – including cutaneous squamous cell carcinoma (CSCC), basal cell carcinoma (BCC), non-small cell lung cancer (NSCLC) and cervical cancer – and in various therapeutic combinations. Cemiplimab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.
ISA101 is an SLP immunotherapy based on the delivery of oncogenic antigens in the form of synthetic long peptides and targets HPV-induced diseases. This innovative concept was discovered by emeritus professor Cornelis J. M. Melief and his team at the Leiden University Medical Center and has been the subject of multiple studies and peer-reviewed publications. It is ISA´s most advanced clinical-stage immunotherapeutic and is in clinical development in advanced and recurrent cervical cancer and incurable HPV16-positive solid tumors (such as squamous cell carcinoma of the head and neck). The first proof-of-concept data on ISA101 as a monotherapy treatment were published in the New England Journal of Medicine2 and initial results from the recently completed ISA101 combination trials in advanced cervical cancer and head-and-neck cancer were presented at ASCO (Free ASCO Whitepaper)-SITC and ESMO (Free ESMO Whitepaper), respectively, in 2017.
WILEX AG: Subsidiary Heidelberg Pharma Signs Exclusive Multi-target Research Agreement with Takeda for the Development of Antibody Targeted Amanitin Conjugates
On June 19, 2017 WILEX AG (ISIN DE000A11QVV0 / WL6 / FSE) reported its subsidiary, Heidelberg Pharma GmbH, Ladenburg, Germany, has signed an exclusive multi-target research agreement with Takeda Pharmaceutical Company Limited (TSE: 4502) for the joint development of antibody drug conjugates (ADCs) that use Amanitin as the payload (Press release, Wilex, JUN 19, 2017, View Source [SID1234526974]).
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Under the terms of the exclusive multi-target research agreement, Heidelberg Pharma will produce Antibody Targeted Amanitin Conjugates (ATACs) using antibodies from Takeda’s proprietary portfolio for up to three undisclosed targets. Takeda has an option for an exclusive license for global development and commercialization rights to each of the product candidates resulting from the research collaboration. If it exercises the option, Takeda would be responsible for further preclinical and clinical development, as well as potential commercialization, of any product candidate it licenses.
Professor Andreas Pahl, Chief Scientific Officer of WILEX AG and Heidelberg Pharma GmbH, commented: "We are delighted about the collaboration with Takeda, which has broad expertise in oncology and is a leading ADC company. We believe this partnership provides further validation of our technology. Working with Takeda will allow us to jointly test and expand the application of the ATAC technology to selected antibodies."
Heidelberg Pharma will receive an upfront technology access fee and payments for research services. In the event Takeda exercises its option for an exclusive license, Heidelberg Pharma would receive an option fee. Under the exclusive license agreement, Heidelberg Pharma would be eligible to receive clinical development, regulatory and sales-related milestone payments of up to USD 113 million for each product candidate, as well as royalties.
The expected financial impact of this partnership is already reflected in WILEX’s financial outlook for the current fiscal year provided in March 2017.
"We see significant potential for Heidelberg Pharma’s ATAC technology, combined with our deep oncology expertise, to develop ADC therapies for patients with unmet medical needs," said Christopher Arendt, PhD, Head, Oncology DDU & Immunology Unit, Takeda. "We are excited about this relationship with Heidelberg Pharma, as partnerships such as this one are integral for us to achieve our aspiration of curing cancer."
Takeda signed the agreement with Heidelberg Pharma through its wholly-owned subsidiary, Millennium Pharmaceuticals, Inc.
About Heidelberg Pharma’s proprietary ATAC technology
Antibody-drug conjugates (ADCs) combine the high affinity and specificity of antibodies with the potency of cytotoxic small molecules for the treatment of cancer and inflammatory diseases. Antibody Targeted Amanitin Conjugates (ATACs) are ADCs whose active ingredient is made up of amatoxin molecules. Amatoxins are small bicyclic peptides naturally occurring in the death cap mushroom. They inhibit mRNA transcription by binding to RNA polymerase II, a mechanism that is crucial for the survival of eukaryotic cells. In preclinical testing, ATACs have been shown to be highly efficacious, overcoming frequently encountered resistance mechanisms and combating even quiescent tumor cells.