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Kancera and Recipharm collaborate to manufacture clinical trial supply

On September 14, 2017 Kancera pharmaceutical reported that KAND567 works by blocking the Fractalkine system and has been shown in preclinical disease models to effectively counteract the onset of autoimmune disorders, as well as neuritis and pain in connection with chemotherapy against cancer (Press release, Kancera, SEP 14, 2017, View Source [SID1234520517]). In future clinical studies, Kancera intends to treat patients with the pharmaceutical candidate KAND567 filled into capsules and taken orally.

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As part of the collaboration, Recipharm will develop the preparation that is required for effective release of KAND567 from the capsules, as well as manufacturing the pharmaceutical product. The work will be performed at Recipharm’s development facility in Solna.

Thomas Olin, CEO of Kancera said: "The decision to commence development of capsules for an active dosage of KAND567 shows that Kancera has reached an important milestone in the Fractalkine project. We are delighted to now be collaborating with Recipharm to produce the pharmaceutical product that will be used to study how KAND567 can help patients."

Torkel Gren, General Manager at Recipharm in Solna commented: "We are happy to be able to contribute to the development of a new drug with the potential to be of great medical value. We have extensive experience in developing drugs for clinical trials as well as commercial manufacture and this will be very valuable in the collaboration with Kancera."

Bayer receives FDA approval for Copanlisib in adults with relapsed follicular lymphoma after two prior systemic therapies (for specialized target groups only)

On September 14, 2017 Bayer reported that the U.S. Food and Drug Administration (FDA) has approved copanlisib under the brand name Aliqopa 60 mg vial for injection for the treatment of adult patients with relapsed follicular lymphoma who have received at least two prior systemic therapies (Press release, Bayer, SEP 14, 2017, View Source [SID1234520516]). Accelerated approval was granted for this indication based on overall response rate (ORR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Copanlisib is a novel intravenous phosphatidylinositol-3-kinase (PI3K) inhibitor with inhibitory activity predominantly against the PI3K-alpha and PI3K-delta isoforms expressed in malignant B cells. The FDA granted approval under the accelerated approval pathway based on data from the open-label, single-arm Phase II CHRONOS-1 [NCT01660451] trial investigating copanlisib in 104 adult patients with follicular B-cell non-Hodgkin’s lymphoma (NHL) who had relapsed disease following at least two prior systemic therapies.

"The U.S. approval of copanlisib in follicular lymphoma is the first of many milestones we look forward to at Bayer across several new promising compounds in our oncology pipeline," said Robert LaCaze, Executive Vice President and Head of the Oncology Strategic Business Unit at Bayer. "We are pleased that the FDA has recognized the promising results of the CHRONOS-1 trial and look forward to offering this important new treatment option to patients with lymphoma, who currently have a high unmet need for effective therapies."

Follicular lymphoma (FL) is the most common subtype of indolent, or slow-growing, non-Hodgkin’s lymphoma (NHL). Response rates and duration of response decline with each line of therapy, underscoring the need for patients whose disease has already progressed.

Developed by Bayer, copanlisib is the only approved PI3K inhibitor with inhibitory activity predominantly against PI3K-alpha and PI3K-delta isoforms expressed in malignant B cells. It is also the only one to be administered intravenously on an intermittent schedule. Copanlisib will be available in the U.S. market immediately.

The New Drug Application for copanlisib received priority review, which is reserved for medicines that would provide significant improvements in the safety or effectiveness of the treatment of serious conditions. The product was approved under FDA regulations 21 CFR Part 314 Subpart H (accelerated approval). The FDA had previously granted copanlisib fast track designation in FL as well as Orphan Drug designation for the treatment of patients with FL and for the treatment of splenic, nodal, and extranodal subtypes of marginal zone lymphoma.

Efficacy and Safety Data Supporting Copanlisib Approval

The Phase II CHRONOS-1 (ClinicalTrials.gov Identifier: NCT01660451) trial included 104 subjects with follicular B-cell non-Hodgkin’s lymphoma (NHL) who had relapsed disease following at least two prior systemic therapies. In the trial, copanlisib achieved an overall response rate (ORR) of 59% [n=104 (95% CI 49, 68)], with 14% of patients achieving a complete response, and a median duration of response of 12.2 months (0+, 22.6). Tumor response was assessed according to the International Working Group response criteria for malignant lymphoma. The primary endpoint was Independent Review Committee-assessed ORR.

Serious adverse reactions were reported in 44 (26%) patients. The most frequent serious adverse reactions that occurred were pneumonia (8%), pneumonitis (5%), and hyperglycemia (5%). Adverse reactions resulted in dose reduction in 36 (21%) and discontinuation in 27 (16%) patients. The most frequently observed adverse drug reactions (≥20%) in copanlisib-treated patients were: hyperglycemia (54%), leukopenia (36%), diarrhea (36%), decreased general strength and energy (36%), hypertension (35%), neutropenia (32%), nausea (26%), thrombocytopenia (22%), and lower respiratory tract infections (21%). The safety data reflect exposure to copanlisib in 168 adults with follicular lymphoma and other hematologic malignancies treated with copanlisb 60 mg or 0.8 mg/kg equivalent in clinical trials. Patients with small lymphocytic leukemia, lymphoplasmacytic lymphoma / Waldenstrom’s macroglobulinemia and marginal zone lymphoma were also enrolled in the study and included in the safety analysis.

About Follicular Lymphoma (FL)
Follicular lymphoma (FL) is the most common histological subtype of indolent, or slow growing, non-Hodgkin’s lymphoma (NHL) that accounts for 22 percent of all newly diagnosed NHL cases worldwide. NHL is the most common hematologic malignancy and the tenth most common cancer worldwide, with nearly 386,000 new cases diagnosed in 2012.

About Copanlisib (Aliqopa)
Copanlisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3K-alpha and PI3K-delta isoforms expressed in malignant B cells. The PI3K pathway is involved in cell growth, survival and metabolism, and its dysregulation plays an important role in follicular lymphoma. Copanlisib is administered as a 1-hour intravenous infusion on days 1, 8, and 15 of a 28-day treatment cycle on an intermittent schedule. Treatment should be continued until disease progression or unacceptable toxicity.

The broad clinical development program for copanlisib also includes ongoing Phase III studies in indolent NHL (iNHL) patients who have relapsed or are refractory to prior therapies. The CHRONOS-3 Phase III study is evaluating copanlisib in combination with rituximab in relapsed iNHL and the CHRONOS-4 Phase III study is evaluating copanlisib in combination with standard immunochemotherapy in relapsed iNHL. More information about these trials can be found at www.clinicaltrials.gov.

Copanlisib is currently not approved by the European Medicines Agency (EMA) or other authorities outside of the U.S.

FDA Approves Amgen And Allergan’s MVASIâ„¢ (bevacizumab-awwb) For The Treatment Of Five Types Of Cancer

On September 14, 2017 Amgen (NASDAQ: AMGN) and Allergan plc. (NYSE: AGN) reported that the U.S. Food and Drug Administration (FDA) has approved MVASI (bevacizumab-awwb) for all eligible indications of the reference product, Avastin (bevacizumab) (Press release, Amgen, SEP 14, 2017, View Source [SID1234520515]). MVASI is the first anti-cancer biosimilar, as well as the first bevacizumab biosimilar, approved by the FDA. MVASI is approved for the treatment of five types of cancer, including in combination with chemotherapy for non-squamous non-small cell lung cancer (NSCLC), in combination with chemotherapy for metastatic colorectal cancer (mCRC), glioblastoma, metastatic renal cell carcinoma in combination with interferon alfa and in combination with chemotherapy for persistent, recurrent, or metastatic carcinoma of the cervix.

"The approval of MVASI marks a significant milestone for healthcare practitioners and patients as the first anti-cancer biosimilar approved in the United States," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "With decades of experience in oncology and biologics, Amgen continues to expand its biosimilar and oncology portfolios, and MVASI has the potential to advance access to high-quality, targeted cancer therapy."

Amgen is committed to developing high-quality biosimilars with a robust analytic and clinical package. Approval is based on the totality of evidence which includes structure, function, toxicity, pharmacokinetics, pharmacodynamics, immunogenicity, clinical safety and efficacy.1 The approval of MVASI was based on a comprehensive data package that demonstrated MVASI and bevacizumab are highly similar, with no clinically meaningful differences in terms of the efficacy, safety and immunogenicity between the products. Clinical studies included results from a Phase 3 trial in patients with NSCLC.

"MVASI is the first product from our collaboration with Amgen to be approved by the FDA and underscores our joint commitment to bring cancer biosimilars to market to help patients," said David Nicholson, chief research and development officer at Allergan. "We are committed to developing safe and effective therapies in critical disease areas, and MVASI is leading the way for additional oncology biosimilars from Amgen and Allergan."

Amgen and Allergan’s bevacizumab biosimilar is also undergoing review by the European Medicines Agency, following a Marketing Authorization Application submitted in December 2016. The companies are collaborating on the development and commercialization of four oncology biosimilars. Amgen has a total of 10 biosimilars in its portfolio, two of which have been approved by the FDA including MVASI.

About MVASI (bevacizumab-awwb) in the U.S.

MVASI is a biosimilar to bevacizumab, a recombinant immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to vascular endothelial growth factor (VEGF) and inhibits the interaction of VEGF with its receptors, VEGF receptor-1 and VEGF receptor-2, thus inhibiting establishment of new blood vessels necessary for the maintenance and growth of solid tumors.

MVASI is indicated for the treatment of mCRC, with intravenous 5-fluorouracil–based chemotherapy for first- or second-line treatment.

MVASI is indicated for the treatment of mCRC, with fluoropyrimidine- irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab-containing regimen.
MVASI is not indicated for adjuvant treatment of colon cancer.

MVASI is indicated for the treatment of NSCLC, with carboplatin and paclitaxel for first line treatment of unresectable, locally advanced, recurrent or metastatic disease.

MVASI is indicated for the treatment of glioblastoma, as a single agent for adult patients with progressive disease following prior therapy.
The effectiveness of bevacizumab products in glioblastoma is based on an improvement in objective response rate. There are no data demonstrating an improvement in disease-related symptoms or increased survival with bevacizumab products.

MVASI is indicated for the treatment of metastatic renal cell carcinoma with interferon alfa.

MVASI is indicated for the treatment of cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan in persistent, recurrent, or metastatic disease.

MVASI U.S. Important Safety Information

Boxed WARNINGS

Gastrointestinal (GI) Perforations

The incidence of gastrointestinal perforation, some fatal, in bevacizumab product-treated patients ranges from 0.3-3.2%. Fatal outcome was reported in <1% of bevacizumab-treated patients. Discontinue MVASI in patients with gastrointestinal perforation.

Surgery and Wound Healing Complications

The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in bevacizumab product-treated patients. Discontinue MVASI in patients with wound dehiscence. The appropriate interval between termination of bevacizumab products and subsequent elective surgery required to reduce the risks of impaired wound healing/wound dehiscence has not been determined. Discontinue at least 28 days prior to elective surgery. Do not initiate MVASI for at least 28 days prior to elective surgery. Do not initiate MVASI for at least 28 days after surgery and until the surgical wound is fully healed.

Hemorrhage

Severe or fatal hemorrhage, including hemoptysis, gastrointestinal bleeding, central nervous system hemorrhage, epistaxis, and vaginal bleeding occur up to 5-fold more frequently in patients receiving bevacizumab products. Across indications, the incidence of grade ≥3 hemorrhagic events among patients receiving bevacizumab ranged from 0.4% to 6.9%. Do not administer MVASI to patients with serious hemorrhage or recent hemoptysis (≥1/2 tsp of red blood). Discontinue MVASI in patients with serious hemorrhage (ie, requiring medical intervention).

Additional serious adverse events

Additional serious and sometimes fatal adverse events with increased incidence in the bevacizumab product-treated arm vs control included
GI fistulae (up to 2% in metastatic colorectal cancer)
Non-GI fistulae (<1% in trials across various indications; 1.8% in a cervical cancer trial)
Arterial thromboembolic events (grade ≥3, 2.6%)
Proteinuria (nephrotic syndrome, <1%)
Additional serious adverse events with increased incidence in the bevacizumab product-treated arm vs control included
GI-vaginal fistulae occurred in 8.3% of patients in a cervical cancer trial
Venous thromboembolism (grade 3-4, up to 10.6%) in patients with persistent, recurrent, or metastatic cervical cancer treated with chemotherapy and bevacizumab product
Hypertension (grade 3-4, 5%-18%)
Posterior reversible encephalopathy syndrome (PRES) (<0.5%)
Infusion reactions with the first dose of bevacizumab product-treated patients were uncommon (<3%), and severe reactions occurred in 0.2% of patients
Inform females of reproductive potential of the risk of ovarian failure prior to starting treatment with MVASI
Pregnancy warning

Based on the mechanism of action and animal studies, bevacizumab products may cause fetal harm
Advise female patients that MVASI may cause fetal harm, and to inform their healthcare provider of a known or suspected pregnancy
Advise females of reproductive potential to use effective contraception during treatment with MVASI and for 6 months after the last dose of MVASI
Advise nursing women that breastfeeding is not recommended during treatment with MVASI
MVASI may impair fertility
Most Common Adverse Events

Across indications, the most common adverse reactions observed in bevacizumab product-treated patients at a rate of >10% and at least twice the control arm rate were: epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis
Across all studies, bevacizumab product was discontinued in 8.4% to 21% of patients because of adverse reactions.
Please see full Prescribing Information, including Boxed WARNINGS, at www.Amgen.com.

Oncolytics Biotech® Announces First Patient Treated in MUK eleven Study

On September 14, 2017 Oncolytics Biotech Inc. (TSX: ONC) (OTCQX: ONCYF) (Oncolytics or the Company), a biotech company developing REOLYSIN (pelareorep), a first-in-class, systemically delivered immuno-oncolytic virus that activates the innate and adaptive immune systems, reported that the first patient has been treated in the Phase 1b trial MUK eleven, studying REOLYSIN in combination with Celgene Corporation’s immunomodulatory drugs (IMiDs), Revlimid or Imnovid as a rescue treatment in relapsing myeloma patients (Press release, Oncolytics Biotech, SEP 14, 2017, View Source [SID1234520513]).

"This is an important trial for Oncolytics as it’s the first to discretely examine the innate immunity component of REOLYSIN’s mechanism of action," said Dr. Matt Coffey, President and CEO of Oncolytics Biotech. "MUK eleven and REO 024, our trial evaluating the induction of an inflamed tumor phenotype of REOLYSIN in a combination with Keytruda, collectively demonstrate our strategy to assess the safety and efficacy of REOLYSIN in combination with immunomodulatory and immuno-oncology drugs, the impact of these combinations on the immune system and to explore new clinical applications."

"We are pleased to have enrolled the first patient in MUK eleven, a trial focused on a novel area of myeloma research," said Dr. Simon Ridley, Director of Research at Myeloma UK. "Our Clinical Trial Network is focused on strategic, collaborative and innovative approaches to delivering trials and treatments to patients and this pioneering trial has the potential to offer a novel future treatment strategy in myeloma."

MUK eleven is a first-of-its-kind immunotherapy trial that aims to modulate the immune system to target myeloma. The trial, run through the Myeloma UK Clinical Trial Network (CTN) in collaboration with charity Myeloma UK, the University of Leeds and Celgene, launched in March of this year and will recruit approximately 44 patients across up to eight CTN centres in the UK. MUK eleven will study REOLYSIN (pelareorep) in combination with Celgene’s Imnovid (pomalidomide) or Revlimid (lenalidomide) in patients whose myeloma is progressing while being treated with one of these IMiDs. In addition to assessing the safety and tolerability of these combinations, the trial will investigate whether the addition of REOLYSIN extends disease control in this patient group.

MUK eleven is a dose escalation trial where dose limiting toxicities (DLTs) will inform decisions to increase dose, and patients being treated with pomalidomide will be evaluated separately from those taking lenalidomide. Beginning at two CTN centres, cohorts of two participants each will be treated with REOLYSIN in combination with an IMiD. The first patient will receive one 28-day treatment cycle and if no DLTs are experienced at the end of the cycle, the second patient will begin treatment at the same dose. Doses may be escalated once participants in each cohort have completed the DLT monitoring period and will be increased between cohorts until the occurrence of DLTs define the maximum tolerated dose (MTD). Once the MTD has been identified with no associated safety issues, 10 additional patients will be enrolled at the MTD. Once a minimum of 12 patients in each IMiD group have been treated, up to six additional trial sites may be added to the trial. Based on this trial design, preliminary data are expected to be available in the first quarter of 2018.

About REOLYSIN
REOLYSIN is a non-pathogenic, proprietary isolate of the unmodified reovirus. A first-in-class systemically delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers.

Atossa Genetics Announces Preliminary Results from Phase 1 Study of Topical Endoxifen

On September 14, 2017 Atossa Genetics Inc. (NASDAQ:ATOS), a clinical-stage pharmaceutical company developing novel therapeutics and delivery methods for breast cancer and other breast conditions, reported preliminary results from its Phase 1 dose escalation study of its proprietary topical Endoxifen (Press release, Atossa Genetics, SEP 14, 2017, View Source [SID1234520512]). All objectives were successfully met:

Safety: There were no clinically significant safety signals and no clinically significant adverse events in participants receiving topical Endoxifen.

Tolerability: Topical Endoxifen was well tolerated at each dose level and for the dosing duration utilized in the study.

Pharmacokinetics: Topical Endoxifen crossed the skin barrier when applied daily to the breast, as demonstrated by low but measurable Endoxifen blood levels detected in a dose-dependent fashion.
These data demonstrate the suitability of topical endoxifen for further clinical development.

Atossa expects to announce results from the oral arm of the Phase 1 study in the next 30-60 days.

The Phase 1 Study

The Phase 1 study was a double-blind, placebo-controlled, repeat dose study of 48 healthy female subjects. Atossa assessed safety, tolerability and the pharmacokinetics of proprietary formulations of both topical and oral Endoxifen dosage forms in varying dose levels over 28 days. The study was conducted in two parts based on route of administration. Results from the oral arm of the study are expected in the next 30 to 60 days.

Atossa’s Proprietary Endoxifen

Endoxifen is an active metabolite of tamoxifen. Tamoxifen is an FDA-approved drug to prevent new breast cancer as well as recurrent breast cancer in breast cancer patients. Tamoxifen itself must be broken down by the liver into active compounds (metabolites), of which Endoxifen is the most active.

Topical Endoxifen. A condition called breast density (or, MBD), typically diagnosed by a mammogram, has been shown to be an independent breast cancer risk factor. To date, 30 states require that findings of MBD be directly communicated to the patient. We believe a topical form of Endoxifen could potentially reduce MBD. Although oral tamoxifen has been shown to reduce MBD, the benefit-cost ratio is not acceptable to most physicians and their patients. For example, it is estimated that only ~ 2% of women at high-risk of developing breast cancer including those with MBD take oral tamoxifen to prevent breast cancer because of the risk of, or actual side-effects of, oral tamoxifen. Therefore we expect our next study to focus on the potential for Atossa’s topical Endoxifen to reduce MBD.

Oral Endoxifen. Although approximately one million breast cancer survivors take tamoxifen annually, up to half of them do not benefit from tamoxifen, meaning they are "refractory," for a number of reasons including that they do not properly metabolize tamoxifen. Low endoxifen levels in breast cancer patients taking oral tamoxifen are associated with an increased risk of recurrence or the development of new breast tumors. Thus providing oral Endoxifen directly to the patient without having to be metabolized may help to address this problem.

Based on the number of women at high-risk of developing breast cancer and the number of patients who have survived breast cancer but are not benefiting from tamoxifen, Atossa estimates that the potential markets for its proprietary oral and topical formulations of Endoxifen could each potentially exceed $1 billion in annual sales.

Next Steps

"Based on these positive preliminary results, we are advancing our topical Endoxifen into Phase 2 studies," commented Dr. Steven C. Quay, CEO and President. "We look forward to announcing the results from the oral arm of our Phase 1 study in the coming 30 to 60 days," continued Dr. Quay.

Breast Cancer Statistics

The American Cancer Society (ACS) estimates that approximately 250,000 women will be diagnosed with breast cancer in the United States this year and that approximately 40,000 will die from the disease. It is the second leading cause of cancer death in American women. Although about 100 times less common than women, breast cancer also affects men. The ACS estimates that the lifetime risk of men getting breast cancer is about 1 in 1,000; 2,470 new cases of invasive breast cancer will be diagnosed; and 460 men will die from breast cancer in 2017.