On April 19, 2017 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that ZEJULA (niraparib), an oral, once-daily poly(ADP-ribose) polymerase (PARP) inhibitor, is now available by prescription in the United States (Press release, TESARO, APR 19, 2017, View Source [SID1234518621]). The U.S. Food and Drug Administration (FDA) approved ZEJULA on March 27, 2017 for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response (CR or PR) to platinum-based chemotherapy. The National Comprehensive Cancer Network (NCCN) recently added ZEJULA to the NCCN Clinical Practice Guidelines in Oncology Ovarian Cancer version 1.2017—April 12, 2017—as maintenance therapy for patients with platinum-sensitive disease who are in partial or complete response after completion of two or more lines of platinum-based therapy. Schedule your 30 min Free 1stOncology Demo! "TESARO is committed to the responsible development and commercialization of transformative therapies for people bravely facing cancer, and we are proud to bring ZEJULA to women who until today had limited treatment options," said Lonnie Moulder, CEO of TESARO. "Increasing progression-free survival after platinum therapy is a truly meaningful benefit for patients and their families, and the once-daily, individualized dosing of ZEJULA allows healthcare providers to ensure the optimal dose per patient without compromising efficacy. We are committed to ensuring access for patients through TOGETHER with TESARO, our patient assistance program for ZEJULA, and we look forward to delivering this important new treatment option to patients and their caregivers."
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ZEJULA is the only PARP inhibitor that has demonstrated a clinically meaningful increase in progression-free survival (PFS) in women with recurrent ovarian cancer, regardless of BRCA mutation or biomarker status, in a randomized, prospectively designed Phase 3 clinical trial. ZEJULA offers oral, once-daily dosing, enabling convenient administration for maintenance treatment. FDA approval of ZEJULA is based upon data from the international Phase 3 ENGOT-OV16/NOVA trial, a double-blind, placebo-controlled study that enrolled 553 patients with recurrent ovarian cancer who had achieved either a PR or CR to their most recent platinum-based chemotherapy. Approximately two-thirds of study participants did not have germline BRCA mutations. Progression in the NOVA study was determined by robust, unbiased, blinded central review, to be the earlier of radiographic or clinical progression. ZEJULA significantly increased PFS in patients with and without germline BRCA mutations as compared to control. Treatment with ZEJULA reduced the risk of disease progression or death by 74% in patients with germline BRCA mutations (HR 0.26) and by 55% in patients without germline BRCA mutations (HR 0.45). The magnitude of benefit was similar for patients entering the trial with a PR or a CR.
The most common grade 3/4 adverse reactions to ZEJULA in the NOVA trial included thrombocytopenia (29%), anemia (25%), neutropenia (20%), and hypertension (9%). The majority of hematologic adverse events were successfully managed via dose modification, and discontinuation of therapy due to thrombocytopenia, neutropenia and anemia occurred in 3.3%, 1.9% and 1.4% of patients, respectively. Following dose adjustment based on individual tolerability, the incidence of grade 3/4 thrombocytopenia was low; approximately <1% after month 2. Please see the "Select Important Safety Information" below for warnings, precautions and adverse events.
"Women with recurrent ovarian cancer often experience considerable fear and anxiety about future recurrences," said Audra Moran, President and CEO of Ovarian Cancer Research Fund Alliance. "ZEJULA may offer patients and their families a treatment option during this stressful period. The ovarian cancer community is eager for new treatment options, and we are glad that ZEJULA will be available to women that have completed their platinum-based chemotherapy."
The Wholesale Acquisition Cost (WAC) of ZEJULA is $9,833 for a one-month supply of ZEJULA at a dose of 200 milligrams once per day, the most commonly administered dose over the course of the Phase 3 NOVA clinical trial. The approved starting dose of ZEJULA is 300 milligrams once per day.
TESARO is committed to ensuring access to ZEJULA. The Company’s patient assistance program, TOGETHER with TESARO, is a reflection of TESARO’s commitment to the patient community and includes comprehensive services such as commercial copay assistance, assistance for the uninsured or underinsured, and access to other organizations that support ovarian cancer patients, among others.
About TOGETHER with TESARO
TOGETHER with TESARO is a patient resource program dedicated to supporting people living with cancer. The program assists with access issues, so that patients with cancer can be free to focus on treatment goals and simply living life. It provides a full suite of services to meet each patient’s needs and individual experience. A team of access and affordability experts is available to help oncology practices and patients gain access to the medication they require. TOGETHER with TESARO will continue to evolve and grow to meet provider and patient needs. For more information, please visit www.togetherwithtesaro.com or call 1-844-2TESARO (1-844-283-7276).
About Ovarian Cancer
Approximately 22,000 women are diagnosed with ovarian cancer each year in the United States, and more than 65,000 women are diagnosed annually in Europe. Ovarian cancer is the fifth-most frequent cause of cancer death among women. Despite high response rates to platinum-based chemotherapy in the second-line advanced treatment setting, approximately 85% of patients will experience recurrence within two years. Per NCCN guidelines, BRCA testing and genetic counseling remain important components of the medical workup for all patients upon a diagnosis with ovarian cancer.
About the ZEJULA (Niraparib) ENGOT-OV16/NOVA Clinical Trial
ENGOT-OV16/NOVA was a double-blind, placebo-controlled, international Phase 3 trial of niraparib that enrolled 553 patients with recurrent ovarian cancer who were in a response to their most recent platinum-based chemotherapy. Patients were enrolled into one of two independent cohorts based on germline BRCA mutation status. One cohort enrolled patients who were germline BRCA mutation carriers (gBRCAmut), and the second cohort enrolled patients who were not germline BRCA mutation carriers (non-gBRCAmut) and included patients with HRD-positive and HRD-negative tumors. Within each cohort, patients were randomized 2:1 to receive niraparib or placebo and were treated continuously with placebo or 300 milligrams of niraparib, dosed as three 100 milligram tablets once per day, until progression. The primary endpoint of this study was progression-free survival (PFS). Secondary endpoints included patient-reported outcomes, chemotherapy-free interval length, PFS 2, overall survival, and other measures of safety and tolerability. More information about this trial is available at View Source
Among patients who were germline BRCA mutation carriers, the niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS, with a hazard ratio of 0.26 (95% CI, 0.173-0.410). The median PFS for patients treated with niraparib was 21.0 months, compared to 5.5 months for control (p<0.0001). Niraparib also showed statistical significance for patients in the non-germline BRCA mutant cohort. The niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS, with a hazard ratio of 0.45 (95% CI, 0.338-0.607). The median PFS for patients treated with niraparib was 9.3 months, compared to 3.9 months for control (p<0.0001). Secondary endpoint analyses, including chemotherapy-free interval, time to first subsequent treatment, and PFS 2 were all statistically significant and favored niraparib over control for patients in both the gBRCAmut and non-gBRCAmut cohorts. Patient-reported outcome results from validated survey tools indicated that niraparib-treated patients reported no difference from control in measures associated with quality of life.
The full results of the ENGOT-OV16/NOVA trial were presented in detail at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress in Copenhagen on October 8, 2016 by Dr. Mansoor Raza Mirza, M.D., Medical Director of the Nordic Society of Gynecologic Oncology (NSGO) and principal investigator. These data were simultaneously published in the New England Journal of Medicine.
Select Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in patients treated with ZEJULA in all clinical studies. Discontinue ZEJULA if MDS/AML is confirmed.
Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients treated with ZEJULA. Do not start ZEJULA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time.
Hypertension and hypertensive crisis have been reported in patients treated with ZEJULA. Monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for six months after receiving the final dose. Because of the potential for serious adverse reactions in breastfed infants from ZEJULA, advise a lactating woman not to breastfeed during treatment with ZEJULA and for one month after receiving the final dose.
In clinical studies, the most common adverse reactions included: thrombocytopenia, anemia, neutropenia, nausea, constipation, vomiting, abdominal pain/distension, mucositis/stomatitis, diarrhea, fatigue/asthenia, decreased appetite, headache, insomnia, nasopharyngitis, dyspnea, rash and hypertension.
Please see full Prescribing Information for additional Safety Information at www.zejula.com.
Additional Clinical Trials of Niraparib
TESARO is building a robust niraparib franchise by assessing activity across multiple tumor types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development program for niraparib includes a Phase 3 trial in patients who have received first-line treatment for ovarian cancer (the PRIMA trial) and a registrational Phase 2 trial in patients who have received multiple lines of treatment for ovarian cancer (the QUADRA trial). Several combination studies are also underway, including trials of niraparib plus pembrolizumab (the TOPACIO trial) and niraparib plus bevacizumab (the AVANOVA trial).
Additional trials of niraparib in ovarian, breast and lung cancers are planned. The studies will assess the effect of niraparib alone and in combination with other therapies, such as bevacizumab and an anti-PD-1 antibody, in a variety of treatment settings.
Janssen Biotech has licensed rights to develop and commercialize niraparib specifically for patients with prostate cancer worldwide, except in Japan.
About ZEJULA (Niraparib)
ZEJULA is an oral, once-daily poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor that is indicated in the U.S. for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. The National Comprehensive Cancer Network (NCCN) recently added ZEJULA to the NCCN Clinical Practice Guidelines in Oncology Ovarian Cancer version 1.2017—April 12, 2017—as maintenance therapy for patients with platinum-sensitive disease who are in partial or complete response after completion of 2 or more lines of platinum-based chemotherapy. In preclinical studies, ZEJULA concentrates in the tumor relative to plasma, delivering greater than 90% durable inhibition of PARP 1/2 and a persistent antitumor effect.
SYROS TO PRESENT ON SY-1425, ITS FIRST-IN-CLASS SELECTIVE RARΑ AGONIST, IN ORAL PLENARY SESSION AT AACR HEMATOLOGIC MALIGNANCIES CONFERENCE
On April 18, 2017 Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of disease-driving genes, reported that the Company will present new preclinical data on SY-1425, its oral first-in-class selective retinoic acid receptor alpha (RARα) agonist currently in a Phase 2 clinical trial in genomically defined subsets of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) (Press release, Syros Pharmaceuticals, APR 19, 2017, View Source [SID1234518617]). These data were selected for oral presentation during a plenary session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Hematologic Malignancies: Translating Discoveries to Novel Therapies conference taking place from May 6-9 in Boston. Schedule your 30 min Free 1stOncology Demo! Details on the plenary talk and corresponding poster presentation are as follows:
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Presentation Title: SY-1425 (tamibarotene), a potent and selective RARα agonist, induces changes in the transcriptional regulatory circuit of AML cells leading to differentiation
Presenter: Christopher Fiore, Ph.D., Scientist, Syros Pharmaceuticals
Date & Time of Plenary Session: Sunday, May 7, from 10:30 a.m. – 1 p.m.
Plenary Session 3: Chemical Biology
Location: Westin Boston Waterfront, Harbor Ballroom 3
Date & Time of Poster Presentation: Sunday, May 7, from 1 – 3 p.m.
Location: Westin Boston Waterfront, Harbor Ballroom 1-2, Poster Board Number 06
Kura Oncology Granted U.S. Patent for Clinical-Stage ERK Inhibitor, KO-947
On April 19, 2017 Kura Oncology, Inc. (NASDAQ:KURA), a clinical stage biopharmaceutical company focused on the development of precision medicines for oncology, reported issuance of a U.S. patent for KO-947, its drug candidate targeting extracellular-signal-regulated kinases (ERK) (Press release, Kura Oncology, APR 19, 2017, View Source [SID1234518614]). The new patent, U.S. 9,624,228, entitled "Inhibitors of ERK and Methods of Use," covers KO-947 and structurally-related compounds as well as methods of using the compounds for the treatment of diseases including cancer. Schedule your 30 min Free 1stOncology Demo! "We believe KO-947 holds much promise as a potential therapeutic, and we were pleased to have advanced it into Phase 1 clinical testing earlier this month," said Troy Wilson, Ph.D., J.D., President and CEO of Kura Oncology. "Issuance of this composition of matter patent is an important development for Kura and the program."
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About KO-947
KO-947 is a potent and selective small molecule ERK1/2 inhibitor. KO-947 exhibits potent anti-proliferative activity across a broad panel of tumor cell lines with mutations in BRAF, NRAS or KRAS and demonstrates prolonged pathway inhibition, both in vitro and in vivo. Durable tumor regression has been observed with KO-947 in preclinical cell line and patient derived xenograft models, including KRAS- and BRAF-mutant adenocarcinomas and squamous cell carcinomas lacking BRAF/RAS mutations.
CytRx Announces FDA Agreement on Regulatory Pathway to Approval for Aldoxorubicin in Soft Tissue Sarcomas
On April 19, 2017 CytRx Corporation (NASDAQ: CYTR) reported the U.S. Food and Drug Administration (FDA) has reached an agreement with CytRx on preparations for a New Drug Application (NDA) submission for aldoxorubicin in soft tissue sarcomas (STS) (Press release, CytRx, APR 19, 2017, View Source;p=RssLanding&cat=news&id=2262830 [SID1234518613]). STS remains a high unmet medical need.
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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
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"We are very pleased to have achieved clarity from the FDA regarding CytRx’s soft tissue sarcoma program," said Daniel Levitt, MD, PhD, Chief Operating Officer and Chief Medical Officer. "The FDA agreed that CytRx could use the application pathway for its filing that has been successfully used previously by the oncology drugs Abraxane, Doxil and Onivyde. Our interaction with the FDA was part of a continued collaborative and productive relationship with the Agency. We look forward to providing the study reports and analysis that can lead to the approval of aldoxorubicin for the treatment of patients with soft tissue sarcomas."
The Company’s goal is to submit a rolling NDA under section 505(b)(2) to the FDA for soft tissue sarcomas in the last quarter of 2017. CytRx also plans to discuss with the European Medicines Agency (EMA) a path to filing a Marketing Authorization Application (MAA). The commercial launch of aldoxorubicin is still projected for 2018 in the United States. Aldoxorubicin has received Orphan Drug Designation by the FDA for the treatment of STS. Orphan designation provides several benefits including seven years of market exclusivity after approval, certain R&D related tax credits and protocol assistance by the FDA. European regulators granted aldoxorubicin Orphan Medicinal Product Designation for STS which confers ten years of market exclusivity among other benefits.
The proposed product label would include the treatment of soft tissue sarcomas. New data could allow future use of aldoxorubicin in neoadjuvant (pre-surgery) settings, as well as a replacement for doxorubicin in combinations. CytRx is also working on a market expansion strategy which could include other indications for aldoxorubicin including combinations with other chemotherapeutics and immunotherapies.
CytRx is under confidentiality agreements with a number of companies for a commercial partnership for the marketing of aldoxorubicin. The Company believes those active discussions may be further advanced by this latest news.
About a 505(b)(2) New Drug Application
A new drug application (NDA) under the Food and Drug Administration’s (FDA) section 505(b)(2) is for a new drug containing similar active ingredients as a previously approved drug. According to the publication Regulatory Focus, a drug reviewed under 505(b)(2) represents a modified version of a previously approved product that requires additional clinical and nonclinical studies, other than bioavailability/bioequivalence studies, to demonstrate safety and efficacy. Such an application differs from a typical NDA in that the sponsor can rely on, at least in part, the FDA’s findings of safety and/or effectiveness for a previously approved reference drug.
About the Phase 2b and Phase 3 Clinical Trials
The Phase 2b trial involved 123 patients at 31 sites. Patients with advanced soft tissue sarcomas were randomized 2:1 to receive either 350 mg/m2 of aldoxorubicin (83 patients) or 75 mg/m2 of doxorubicin (40 patients) every 3 weeks for up to 6 cycles. The trial was designed to compare aldoxorubicin directly with doxorubicin.
The randomized, controlled Phase 3 trial enrolled a total of 433 patients at 79 clinical sites. Patients with metastatic, locally advanced or unresectable soft tissue sarcomas who had either not responded to, or who had progressed following treatment with one or more systemic regimens of non-adjuvant chemotherapy were randomized 1:1 to be treated with aldoxorubicin or the investigator’s choice of an approved chemotherapeutic regimen, including doxorubicin, ifosfamide, dacarbazine, pazopanib (Votrient), or gemcitabine plus docetaxel.
About Soft Tissue Sarcoma
Soft tissue sarcoma is a cancer occurring in muscle, fat, blood vessels, tendons, fibrous tissues and connective tissue. It can arise anywhere in the body at any age. STS remains a high unmet medical need because of the difficulty in treating the more than 50 types of this aggressive cancer. According to the American Cancer Society, in 2016 more than 12,300 new cases were diagnosed in the U.S. and approximately 5,000 Americans died from this disease. In addition, approximately 40,000 new cases and 13,000 deaths in the U.S. and Europe are part of a growing underserved market.
About Aldoxorubicin
Aldoxorubicin is a rationally engineered cytotoxic which combines doxorubicin, a widely used chemotherapeutic agent, with a novel linker molecule that binds directly and specifically to circulating albumin, the most abundant protein in the bloodstream. Protein-hungry tumors concentrate albumin, which facilitates the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. Typically, doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Using this acid-sensitive linker technology, aldoxorubicin delivers greater doses of doxorubicin (3 ½ to 4 times). To date, there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of the drug well in excess of 5,000 mg/m2. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized clinical trial in first-line STS.
Aptose Biosciences to Present CG’806 Data at AACR Hematologic Malignancies Meeting
On April 19, 2017 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS), a clinical-stage company developing highly differentiated therapeutics that target the underlying mechanisms of cancer, reported that preclinical data for its pan-FLT3/BTK inhibitor CG’806 will be presented in two separate posters at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference Hematologic Malignancies: Translating Discoveries to Novel Therapies, being held May 6-9 in Boston, MA (Press release, Aptose Biosciences, APR 19, 2017, View Source [SID1234518612]). Schedule your 30 min Free 1stOncology Demo! Aptose is developing CG’806, a first-in-class pan-FLT3/BTK inhibitor, for acute myeloid leukemia (AML) and other hematologic malignancies. CG’806 is a highly potent inhibitor of the wild type and mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and the gatekeeper region), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. In addition, CG’806 is a reversible, non-covalent, inhibitor of the wild type and mutant forms of the BTK enzymes. The spectrum of activity against specific clusters of kinase enzymes supports the development of CG’806 for AML, certain B cell malignancies and other hematologic malignancies.
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Two separate presentations are planned for CG’806. Aptose scientists, with researchers from the Knight Cancer Institute at Oregon Health & Science University (OHSU), will present data related to the potency of CG’806 against various hematologic malignancy cell lines and patient bone marrow specimens. In a separate presentation, Aptose scientists, with researchers from the MD Anderson Cancer Center, will present data demonstrating CG’806’s potent activity against AML cells harboring specific wild type or mutant forms of FLT3.
Abstract Details
Title: "CG’806, a first-in-class FLT3/BTK inhibitor, exhibits potent activity against AML patient samples with mutant or wild-type FLT3, as well as other hematologic malignancy subtypes"
Presenter: Stephen E. Kurtz, Ph.D, Oregon Health & Science University, Portland, OR
Date/Time: May 7, 2017 / 1:00 p.m. ET – 3:00 p.m. ET
Location: Harbor 1/2, Westin Boston Waterfront, Boston, MA
Session: Poster Session
Abstract Details
Title: "CG’806, a first-in-class FLT3/BTK inhibitor, exerts superior potency against AML cells harboring ITD, TKD and gatekeeper mutated FLT3 or wild-type FLT3"
Presenter: Weiguo Zhang, M.D., Ph.D, UT MD Anderson Cancer Center, Houston, TX
Date/Time: May 7, 2017 / 1:00 p.m. ET – 3:00 p.m. ET
Location: Harbor 1/2, Westin Boston Waterfront, Boston, MA
Session: Poster Session
About CG’806
CG’806 is a once daily, oral, first-in-class pan-FLT3/BTK inhibitor. This small molecule demonstrates potent inhibition of mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the Cys481Ser mutant of the BTK enzyme, as well as other oncogenic kinases operative in B cell malignancies, suggesting the CG’806 may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.