On December 20, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported that Janssen Pharmaceutical K.K. has submitted a New Drug Application to the Ministry of Health, Labor and Welfare (MHLW) in Japan for the use of daratumumab (DARZALEX) for the treatment of adults with relapsed or refractory multiple myeloma (Press release, Genmab, DEC 20, 2016, View Source [SID1234517127]). The submission of the application triggers milestone payments totaling USD 10 million to Genmab from Janssen. Genmab is updating its financial guidance for 2016 to include the milestones. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab. Schedule your 30 min Free 1stOncology Demo! "We are pleased that the first regulatory application for daratumumab in the Asia Pacific region has been submitted and look forward to the decision of the Japanese regulatory authorities," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "We continue to be excited by the potential of daratumumab to make a positive impact on the lives of patients with multiple myeloma and their families."
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The submission is built around three pivotal studies: the Phase II SIRIUS study (MMY2002), published in The Lancet in April 2016; the Phase III CASTOR study (MMY3004), published in The New England Journal of Medicine in August 2016; the Phase III POLLUX study (MMY3003), published in The New England Journal of Medicine in October 2016; and supported by several other studies.
OUTLOOK
MDKK Revised Guidance Previous Guidance
Revenue 1,720 — 1,770 1,650 — 1,700
Operating expenses (800) — (850) (800) — (850)
Operating income 895 — 945 825 — 875
Cash position at end of year* 3,650 — 3,750 3,650 — 3,750
*Cash, cash equivalents, and marketable securities
Genmab is improving its 2016 financial guidance published on November 21, 2016 due to the inclusion of daratumumab milestones totaling USD 10 million associated with the submission of the regulatory application for daratumumab in relapsed or refractory multiple myeloma in Japan.
Operating Result
We expect our 2016 revenue to be in the range of DKK 1,720 — 1,770 million, an increase of DKK 70 million compared to the previous guidance. We have increased our projected daratumumab milestones to DKK 1,090 million (previously DKK 1,020 million) due to inclusion of USD 10 million in milestone payments triggered by the submission of the regulatory application for daratumumab in relapsed or refractory multiple myeloma in Japan. We expect DARZALEX royalties to remain in the range of DKK 400 — 450 million, which are based on an estimated USD 500 — 550 million of DARZALEX sales in 2016. The remainder of the revenue mainly consists of Arzerra royalties, DuoBody milestones, and non-cash amortization of deferred revenue.
We anticipate that our 2016 operating expenses will remain in the range of DKK 800 — 850 million.
As a result of the increased revenue, we now expect the operating income for 2016 to be approximately DKK 895 – 945 million, compared to DKK 825 – 875 million in the previous guidance.
Cash Position
There is no change to the cash position at the end of 2016 of DKK 3,650 – 3,750 million as we expect to receive payment for the additional milestones shortly after year-end.
Outlook: Risks and Assumptions
In addition to factors already mentioned, the estimates above are subject to change due to numerous reasons, including but not limited to the achievement of certain milestones associated with our collaboration agreements; the timing and variation of development activities (including activities carried out by our collaboration partners) and related income and costs; DARZALEX and Arzerra sales and corresponding royalties to Genmab; fluctuations in the value of our marketable securities; and currency exchange rates. The financial guidance does not include any potential proceeds from future warrant exercises and also assumes that no significant agreements are entered into during 2016 that could materially affect the results.
About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 30,330 new patients are expected to be diagnosed with multiple myeloma and approximately 12,650 people are expected to die from the disease in the U.S. in 2016.3 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5 Patients who relapse after treatment with standard therapies, including proteasome inhibitors or immunomodulatory agents, have poor prognoses and few treatment options.6
About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.7 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. For more information, visit www.DARZALEX.com.
Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells.
Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).7,8,9,10,11
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline multiple myeloma settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, non-Hodgkin’s lymphoma, NKT-cell lymphoma, amyloidosis, and solid tumors. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.
Adaptimmune and Bellicum Pharmaceuticals Enter a Strategic Collaboration to Evaluate Next-Generation T-Cell Therapies
On December 19, 2016 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, and Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported that they have entered into a staged collaboration to evaluate, develop, and commercialize next-generation T-cell therapies (Press release, Adaptimmune, DEC 19, 2016, View Source [SID1234631816]).
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Under the agreement, the companies will evaluate Bellicum’s GoTCR technology (inducible MyD88/CD40 co-stimulation, or iMC) with Adaptimmune’s affinity-optimized SPEAR T-cells for the potential to create enhanced TCR product candidates. Depending on results from the preclinical proof-of-concept phase, the companies expect to progress to a two-target co-development and co-commercialization phase.
"We are committed to advancing our clinical pipeline of proprietary cell therapies and to entering strategic collaborations that can further leverage the unique potential of our controllable T-cell technologies," commented Tom Farrell, President and Chief Executive Officer of Bellicum. "We’re looking forward to working with the Adaptimmune team to create and advance potentially best-in-class TCR therapies."
"As we advance our deep pipeline of second- and third-generation SPEAR T-cell therapies, we are excited by the potential of Bellicum’s iMC switch to complement the activity of our affinity enhanced T-cell therapies, as part of our continuing initiative to assess novel cell therapy enhancement technologies," said James Noble, Adaptimmune’s Chief Executive Officer. "This is an innovative field that requires broad, industry-wide collaborations, such as our relationship with Bellicum and its strong leadership position in switch technology."
About Bellicum’s iMC Technology
Bellicum’s Chemical Induction of Dimerization (CID) technology platform was designed to address the challenges of current cellular immunotherapies by enabling control over cellular activities and functions, such as growth, activation, proliferation, persistence and survival. Bellicum’s CID platform consists of molecular switches—modified forms of signaling proteins—which are triggered inside the patient by infusion of small molecule rimiducid, instead of by natural upstream signals. Current product candidates incorporate either the CaspaCIDe safety switch, or iMC activation switch. After rimiducid is administered, CaspaCIDe is designed to trigger programmed cell death, or apoptosis, and iMC is designed to drive proliferation, activation and/or persistence of T-cells.
About Adaptimmune’s TCR Technology
Adaptimmune’s proprietary SPEAR (Specific Peptide Enhanced Affinity Receptor) T-cell receptor (TCR) technology enables the Company to genetically optimize TCRs in an effort to equip them to recognize and bind cancer antigens that are presented in small quantities on the surface of a cancer cell, whether of intracellular or extracellular origin, thus initiating cell death. The Company’s differentiated, proprietary technology allows it to reliably generate parental TCRs to naturally presented targets, affinity optimize its TCRs to bind cancer proteins from solid and hematologic cancers that are generally unavailable to naturally occurring TCRs, and to significantly reduce the risk of side effects resulting from off-target binding of healthy tissues.
Novocure’s Optune® (NovoTTF-100A) Approved in Japan for the Treatment of Newly Diagnosed Glioblastoma
On December 19, 2016 Novocure (NASDAQ: NVCR) reported that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Optune (NovoTTF-100A) – Novocure’s Tumor Treating Fields (TTFields) delivery system – in the treatment of adult patients with supra-tentorial glioblastoma (GBM) following maximal safe surgical resection and radiation therapy (Press release, NovoCure, DEC 19, 2016, View Source [SID1234517132]). Novocure will prepare to submit an application for public reimbursement of Optune for newly diagnosed GBM in Japan.
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"The Japanese MHLW’s approval of Optune represents an important milestone for Novocure, enabling us to treat more patients who suffer from this aggressive disease," said Novocure CEO Asaf Danziger. "Optune in combination with temozolomide has been clinically proven to extend survival in patients with newly diagnosed GBM, and we look forward to making Optune available to newly diagnosed GBM patients in Japan."
Novocure established commercial operations in Japan in March 2015 after the MHLW approved Optune for the treatment of recurrent GBM. Approximately 1,500 patients are diagnosed with GBM in Japan each year.
"This approval is a significant moment for newly diagnosed GBM patients in Japan," said Ryo Nishikawa, MD, PhD, President of the Japanese Society of Neuro-Oncology and Professor of Saitama Medical University International Medical Center. "Optune provides patients with an additional treatment option, one that has been proven to extend survival."
The MHLW’s approval of Optune for the treatment of newly diagnosed GBM was supported by Novocure’s phase 3 pivotal EF-14 trial results, which showed significant extension of both progression free and overall survival in newly diagnosed GBM patients receiving Optune with temozolomide compared to temozolomide alone. Optune is the first MHLW-approved therapy in more than a decade to demonstrate statistically and clinically significant extension of survival in newly diagnosed GBM patients.
"We have been eagerly anticipating this day," said Shungo Matori, Novocure’s General Manager Japan and Representative Director of Novocure K.K. "Newly diagnosed GBM patients have experienced an unmet need for better treatment options. We are dedicated to making Optune available to all GBM patients who can benefit from our therapy in Japan."
KANCERA REPORTS POSITIVE RESULTS FOR FRACTALKINE BLOCKER KAN0440567 IN PRECLINICAL MODELS OF PAIN CAUSED BY ANTI-CANCER DRUGS
On December 19, 2016 Kancera AB (publ) reported that the drug candidate KAN0440567 quickly and effectively counteracts the kind of pain that results from chemotherapy and that often prevents effective treatment of cancer (Press release, Kancera, DEC 19, 2016, View Source [SID1234517128]). The results also indicate that the Kancera drug candidate inhibits the development of the nerve damage that causes pain.
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Kancera, in collaboration with Professor Malcangio at King’s College, London, showed that oral treatment with the fractalkine blocker KAN0440567 counteracts pain caused by vincristine. Vincristine is a chemotherapy agent used to treat cancers such as acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin’s disease, neuroblastoma and small cell lung cancer.
Pain resulting from chemotherapy often leads to cancer treatment needing to be reduced in intensity or being interrupted before the desired results are achieved (1). Every year about 1.7 million patients are treated with chemotherapy in the United States, Europe and Japan (2). Approximately 80% (3) of these are affected by nerve injury and subsequent pain and a significant proportion of these will have lasting problems that prevent a normal life. Today there is no effective treatment for this type of nerve damage.
In the Kancera study mice were treated with vincristine twice daily for five days, resembling the clinical protocol that can lead to nerve injury and pain. Oral treatment with KAN0440567, 125 mg/kg twice daily, effectively reduced the onset of this pain. From day one the effect was evident in the KAN0440567-treated animals and on days two to five pain was significantly lower than the control group. The study also showed that KAN0440567 did not affect sensitivity to being touched in the control animals, which supports the idea that the Kancera drug candidate specifically inhibits development of nerve damage.
If these effects are also achieved under clinical conditions, KAN0440567 could contribute to more effective cancer treatment since the desired dosage of chemotherapy can be maintained longer with less side effects in the form of nerve damage. Furthermore, reduced long-lasting nerve problems after successful cancer treatment would result in more patients being able to return to a normal life.
What makes KAN0440567 unique is that it works by preventing a special group of immune cells (monocytes) from infiltrating healthy tissue and causing damage, while other parts of the immune system maintain their protective ability. Thus, KAN440567 is likely to be effective in several inflammatory diseases, cancer and pain, without seriously affecting the immune system in general.
1. Windebank AJ and Grisold W (2008) J Per Nerv Syst 13: 27-46
2. IMS
3. Sisignano, M. et al. (2014) Nat Rev Neurol 10, 694–707
About the Fractalkine project Fractalkine is an immune regulatory factor, a so-called chemokine, that sends signals via the CX3CR1 receptor, also called G-protein coupled receptor 13 (GPCR13). The level of fractalkine and its receptor, CX3CR1 has been shown to be elevated in many inflammatory diseases, cancer and in chronic pain conditions. Kancera’s drug candidate KAN0440567 is the furthest developed drug candidate against CX3CR1 and has been shown to be effective against inflammation and pain in several preclinical disease models. Kancera is now preparing the project for clinical studies. In the healthy individual, Fractalkine and its receptor regulate migration of immune cells from the blood capillary wall into areas where the immune system is needed. Animal studies show that Fractalkine’s receptor is not essential for survival and that important immune functions remain intact despite the lack of receptor.The body of research supports the overall hypothesis that CX3CR1 is more crucial to developing disease than to keeping the individual healthy. The basis for successful development of KAN0440567 lies in effectively addressing local inflammation while maintaining a healthy immune system.
Foundation Medicine Receives FDA Approval of FoundationFocus™ CDxBRCA as a Companion Diagnostic for Rubraca™ (rucaparib) for the Treatment of Women with Ovarian Cancer
On December 19, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported that the U.S. Food and Drug Administration (FDA) has approved FoundationFocus CDxBRCA for use as a companion diagnostic to aid in identifying women with ovarian cancer for whom treatment with Rubraca (rucaparib), a therapy developed by Clovis Oncology, Inc., is being considered (Press release, Foundation Medicine, DEC 19, 2016, View Source [SID1234517130]). FoundationFocus CDxBRCA is an FDA-approved tissue-based, genomic assay that uniquely detects tumor BRCA1 and BRCA2 mutations (may include both germline (inherited) and somatic (acquired)) in ovarian cancer. FoundationFocus CDxBRCA may help identify more women who could benefit from Rubraca therapy as compared to conventional testing methods that only identify germline BRCA1/2 mutations. Germline-only BRCA1/2 testing identifies approximately half of all BRCA1/2 mutations.i,ii
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Rubraca is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies, and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.
"These simultaneous approvals by the FDA represent a step forward for women with advanced ovarian cancer, an area where there is a tremendous need for effective therapeutic approaches and efficient ways to identify those most likely to respond to PARP inhibitor therapy," said Michael Pellini, M.D., chief executive officer of Foundation Medicine. "This approval also represents a significant milestone for Foundation Medicine, one that underscores the quality and value of our molecular information solutions to inform patient care and to accelerate and streamline the therapeutic development programs of our biopharmaceutical partners."
Foundation Medicine and Clovis Oncology closely collaborated on a regulatory strategy to develop FoundationFocus CDxBRCA in parallel with the development of Rubraca. Tissue samples taken from individuals with ovarian cancer who enrolled in rucaparib clinical trials were analyzed by Foundation Medicine utilizing comprehensive genomic profiling (CGP) to identify biomarkers associated with a response to therapy. These molecular signatures of response informed the development of FoundationFocus CDxBRCA, which was utilized in Clovis’ pivotal trial, ARIEL2, to identify patients and accelerate recruitment into the study. The companies filed concurrent pre-market approval (PMA) and new drug application (NDA) submissions with the FDA earlier this year.
With this FDA approval, FoundationFocus CDxBRCA is the first validated, tissue-based assay developed from the Quality Systems Regulations (QSR)-compliant version of Foundation Medicine’s CGP assay, providing uniform analysis of all BRCA1/2 coding exons.
Dr. Pellini continued, "FDA approval of our first companion diagnostic assay also represents an important advance in our efforts to utilize our rigorously validated CGP approach to deliver a universal companion diagnostic assay. We believe this approach may enable the efficient delivery of personalized cancer care by eliminating the guesswork for physicians through a comprehensive view of companion diagnostic claims, as well as potential treatment options based on guidelines, peer reviewed literature and clinical trials."
As part of the company’s effort to develop a universal companion diagnostic, earlier this year, Foundation Medicine announced that FoundationOne, the company’s CGP assay for solid tumors, was accepted by the FDA and the Centers for Medicare and Medicaid Services (CMS) for Parallel Review. The FDA also granted Foundation Medicine’s request for review as part of its Expedited Access Pathway for breakthrough devices. If approved, FoundationOne would be an FDA-approved CGP assay that incorporates multiple companion diagnostics to support precision medicine in oncology, including an indication for use as a companion diagnostic across a diverse range of solid tumors, which is anticipated to include ovarian cancer.
More than 22,000 women will potentially be diagnosed with ovarian cancer in the U.S. during 2016.iii Ovarian cancer is the leading cause of female gynecologic cancer-related deathsiv and one in four women with ovarian cancer have a germline or somatic BRCA mutation.ii
About FoundationFocus CDxBRCA
Intended Use: FoundationFocus CDxBRCA is a next generation sequencing test for qualitative detection of BRCA1 and BRCA2 (BRCA1/2) alterations in formalin-fixed paraffin-embedded (FFPE) ovarian tumor tissue. The FoundationFocus CDxBRCA assay detects sequence alterations in BRCA1/2 genes. Results of the test are used as an aid in identifying ovarian cancer patients for whom treatment with Rubraca (rucaparib) is being considered. If a patient is positive for any of the deleterious alterations specified in the BRCA1/2 classification, the patient may be eligible for treatment with Rubraca. This assay is to be performed at Foundation Medicine, Inc., a single laboratory site located at 150 Second Street, Cambridge, MA 02141. For more information about FoundationFocus CDxBRCA assay, visit View Source