On February 19, 2019 Pfizer Inc. (NYSE: PFE) reported the European Commission (EC) has approved ZIRABEV for the treatment of metastatic carcinoma of the colon or rectum, metastatic breast cancer, unresectable advanced, metastatic or recurrent non-small cell lung cancer (NSCLC), advanced and/or metastatic renal cell cancer and persistent, recurrent or metastatic carcinoma of the cervix.1,2 (Press release, Pfizer, FEB 19, 2019, View Source [SID1234533387])

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"Pfizer is dedicated to increasing access to biosimilars for patients suffering from serious illnesses and helping create a more sustainable healthcare system," said Andreas Penk, M.D., regional president, Oncology International Developed Markets at Pfizer. "We are proud that ZIRABEV was approved today as our second oncology biosimilar in Europe. This milestone reflects our ongoing commitment to biosimilars as we continue to bring high-quality medicines to market that may help generate cost savings for cancer care."

* Avastin is a registered trademark of Genentech

The EC approval is based on a comprehensive submission package which demonstrated biosimilarity of ZIRABEV and the originator product. This includes results from the phase 3 REFLECTIONS B739-03 clinical comparative study, which showed clinical equivalence and found no clinically meaningful differences between ZIRABEV and the originator product in patients with advanced non-squamous NSCLC.3 As part of the overall REFLECTIONS clinical trial program, ZIRABEV has been studied in approximately 400 subjects.3,4

This approval follows the positive recommendation from the Committee for Medicinal Products for Human Use in December 2018.5 ZIRABEV has also been filed for regulatory approval with the U.S. Food and Drug Administration.

Pfizer has a robust portfolio of potential biosimilar candidates in mid- to late-stage development.6 ZIRABEV is Pfizer’s fifth biosimilar approved for use in Europe.1,7, 8,9,10

About ZIRABEV (bevacizumab biosimilar)

ZIRABEV is a monoclonal antibody (mAb) biosimilar of the originator biologic medicine, Avastin, which works by inhibiting the formation of new blood cells (angiogenesis) by specifically recognizing and binding to vascular endothelial growth factor (VEGF) protein.11, 12,13 ZIRABEV has been studied in nearly 400 patients.3,4

ZIRABEV safety information

Do not use ZIRABEV if you are allergic to bevacizumab, any of its ingredients, Chinese hamster ovary (CHO) cell products, or other recombinant human or humanised antibodies, or if you are pregnant.

Before starting treatment with ZIRABEV, tell your healthcare provider if:

you have any conditions causing inflammation inside the abdomen (e.g. diverticulitis, stomach ulcers, colitis associated with chemotherapy)
you have persistent, recurrent or metastatic cervical cancer
you are going to have an operation, if you have had major surgery within the last 28 days or if you still have an unhealed wound following surgery
you had holes in the gut wall or problems with wound healing
you have high blood pressure which is not well controlled with blood pressure medicines
you are over 65 years old, if you have diabetes, or if you have had previous blood clots in your arteries
you or your family tend to suffer from bleeding problems or you are taking medicines to thin the blood for any reason
you have metastatic cancer affecting your brain
you have noticed coughing or spitting blood
you have ever received anthracyclines (for example doxorubicin, a specific type of chemotherapy used to treat some cancers) or had radiotherapy to your chest, or if you have heart disease
you have previously experienced problems after injections, such as dizziness/feeling of fainting, breathlessness, swelling or skin rash
you have headache, vision changes, confusion or seizure with or without high blood pressure
you have or have had pain in the mouth, teeth and/or jaw, swelling or sores inside the mouth, numbness or a feeling of heaviness in the jaw, or loosening of a tooth
you need to undergo an invasive dental treatment or dental surgery, in particular when you are also receiving or have received an injection of bisphosphonate into your blood
you are currently using or recently used a medicine called sunitinib malate, are receiving platinum- or taxane-based chemotherapy (medicines used to treat cancer) or are receiving or recently received radiotherapy
you have previously received any other treatment for cancer
ZIRABEV increases the risk of having protein in your urine, especially if you already have high blood pressure. ZIRABEV can also increase the risk of developing blood clots in your veins (a type of blood vessel) and may cause infections and a decreased number of your neutrophils (a type of blood cell important for your protection against bacteria).

Like all medicines, ZIRABEV can cause side effects, although not everybody gets them. If you have an allergic reaction, contact your doctor or a member of medical staff straight away. The signs may include difficulty in breathing or chest pain. You could also experience redness or flushing of the skin or a rash, chills and shivering, feeling sick (nausea) or being sick (vomiting). Very common severe side effects of treatment with ZIRABEV are:

high blood pressure
the feeling of numbness or tingling in hands or feet
a decreased number of cells in the blood, including white cells that help to fight infection (this may be accompanied by fever), and cells that help the blood to clot
feeling weak and having no energy
tiredness
diarrhoea, nausea, vomiting and abdominal pain.
Other very common side effects that are not as severe include constipation, loss of appetite, fever, problems with eyes (including increased tear production), changes in speech, changes in sense of taste, runny nose, dry skin, flaking and inflammation of skin, changes in skin color, loss of body weight and nose bleeds. You should tell your healthcare provider immediately if you notice any of the above symptoms.

Tell your healthcare provider if you are taking, have recently taken or may take any other medicines.

Tell your healthcare provider if you are pregnant, plan to become pregnant, or are breastfeeding.

Ask your healthcare provider about the risks and benefits of ZIRABEV. Only a healthcare provider can decide if ZIRABEV is right for you.

You are encouraged to report negative side effects to the European Medicines Agency. Visit View Source Please refer to the European Summary of Product Characteristics for ZIRABEV for complete safety information.

On February 19, 2019 MannKind Corporation (Nasdaq:MNKD) reported that it will release its 2018 fourth quarter and full year financial results on Tuesday, February 26, 2019 and its management will host a conference call to discuss the financial results and other Company developments at 9:00 AM (Eastern Time) on February 26, 2019 (Press release, Mannkind, FEB 19, 2019, View Source [SID1234533478]).

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Presenting from the Company will be its Chief Executive Officer, Michael Castagna and Chief Financial Officer, Steven Binder.

To participate in the live call by telephone, please dial (888) 394-8218 or (323) 701-0225 and use the participant passcode: 7809405. Those interested in listening to the conference call live via the Internet may do so by visiting the Company’s website at View Source under News & Events.

A telephone replay of the call will be accessible for approximately 14 days following completion of the call by dialing (844) 512-2921 or (412) 317-6671 and use the participant passcode: 7809405#. A replay will also be available on MannKind’s website for 14 days.

On February 19, 2019 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies for the treatment of cancer, reported that Professor Persis Amrolia, Consultant in Bone Marrow Transplant at Great Ormond Street Hospital (GOSH) and NIHR Research Professor of Transplantation Immunology at University College London (UCL) Great Ormond Street Institute of Child Health, presented updated data from the ongoing Phase 1 CARPALL trial of AUTO1 in a poster presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) 1st European CAR T Cell Meeting held in Paris, France, February 14-16, 2019 (Press release, Autolus, FEB 19, 2019, View Source [SID1234550832]).

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Enrolled patients had a median age of 9 years with a median of 4 lines of prior treatment. Seventeen patients were enrolled, and 14 patients received an infusion of CAR T cells. Ten of 14 patients had relapsed post allogeneic stem cell transplant. Eight patients were treated in second relapse, 5 in >second relapse and 3 had relapsed after prior blinatumomab or inotuzumab therapy. Two patients had ongoing CNS disease at enrollment.

Updated safety results
This data set confirms that AUTO 1 induces no severe cytokine release syndrome (CRS) (Grade 3-5). Nine patients experienced Grade 1 CRS, and 4 patients experienced Grade 2 CRS. No patients required tociluzumab or steroids. As previously reported, one patient experienced Grade 4 neurotoxicity; there were no other reports of severe neurotoxicity (Grade 3-5). The mean cumulative exposure to AUTO1 CAR T cells in the first 28 days as assessed by AUC was 1,721,355 copies/µg DNA. Eleven patients experienced cytopenia that was not resolved by day 28 or recurring after day 28: 3 patients Grades 1-3 and 8 patients Grade 4. Two patients developed significant infections, and 1 patient died from sepsis while in molecular complete response (CR).

Updated efficacy results
With a single dose of CAR T cells at 1 million cells/kg dose, 12/14 (86%) achieved molecular CR. Five patients relapsed with CD19 negative disease. Event free survival (EFS) based on morphological relapse was 67% (CI 34-86%) and 46% (CI 16-72%) and overall survival (OS) was 84% (CI 50-96%) and 63% (CI 27-85%) at 6 and 12 months, respectively.

CAR T cell expansion was observed in all responding patients (N=12), with CAR T cells comprising up to 84% of circulating T cells at the point of maximal expansion. The median persistence of CAR T was 215 days.

The median duration of remission in responding patients was 7.3 months with a median follow-up of 14 months. Five of 14 patients (37%) remain in CR with ongoing persistence of CAR T cells and associated B cell aplasia.

"AUTO1 combines a high molecular CR rate with excellent persistence and a good safety profile in pediatric acute B cell leukemia patients," said Professor Amrolia.

About AUTO1
AUTO1 is a CD19 CAR T cell investigational therapy designed to overcome the limitations in safety – while maintaining similar levels of efficacy – compared to current CD19 CAR T cell therapies. Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, AUTO1 may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the T cells’ abilities to engage in serial killing of target cancer cells. In 2018, Autolus signed a license agreement under which Autolus acquired global rights from UCL Business plc (UCLB), the technology-transfer company of UCL, to develop and commercialize AUTO1 for the treatment of B cell malignancies. AUTO1 is currently being evaluated in two Phase 1 studies, one in pediatric ALL and one in adult ALL.

For information about the CARPALL trial, visit View Source

About Pediatric Acute Lymphoblastic Leukemia (ALL)
According to the American Cancer Society, ALL is the most common cancer diagnosed in children, with approximately 3,400 new cases diagnosed in the United States each year. Pediatric ALL occurs when the bone marrow makes too many immature lymphocytes, which are a type of white blood cell. The current standard of care for pediatric ALL patients is combination chemotherapy. Although pediatric patients typically respond well to first-line treatment, 10 to 20% of total patients relapse with chemotherapy-resistant disease, leading to a significant unmet need in pediatric patients with high-risk relapsed or refractory ALL.

On February 19, 2019 NEW ORLEANS & Ochsner Health System, Louisiana’s largest non-profit academic healthcare system, and Pfizer Inc (NYSE:PFE) reported that have entered into a multi-year strategic alliance to develop innovative models for clinical trials (Press release, Pfizer, FEB 19, 2019, View Source [SID1234533388]). Through this partnership, Pfizer and Ochsner — through its innovation lab, innovationOchsner (iO), in partnership with Ochsner Research — will explore ways to enhance the clinical trial experience and ease participation in clinical research for both patients and healthcare professionals.

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The alliance aims to create faster, improved access and connectivity to clinical trials for patients, with the ultimate goal of better experiences and outcomes. Participating patients will have the opportunity to test out new digital tools designed to make the clinical trial experience more inclusive and enjoyable. Participating clinicians will benefit from reduced manual data entry as a result of direct data system integration and automated study conduct tools, freeing up time and work to allow them to offer clinical research as an option to a broader range of patients. And research groups will experience efficiencies from interoperability that may lower costs while increasing capacity. These projects are designed to ensure that all data collected is secure and will only be used with patient consent, as in any clinical trial.

"As a national leader in healthcare, Ochsner is delivering on its mission to bring the most innovative ideas to our patients. We are relentless about using the latest breakthroughs in science and technology to solve some of the toughest healthcare challenges," said Dr. Richard Milani, Ochsner’s Chief Clinical Transformation Officer and Medical Director of iO. "Partnering with Pfizer allows us to transform medicine by creating a digital clinical trial experience that improves patient participation, integration, communication and accessibility."

The strategic alliance’s first project began with a "proof of value" phase in which researchers successfully transferred mock data (e.g. no actual patient data was used or shared) from Ochsner’s EHR system to Pfizer’s electronic data capture system used in Pfizer clinical trials. The experiment aimed at understanding the gaps and variances between data collected in electronic health records and patient-reported data from clinical trials.

Since the inception of electronic health records (EHRs), integrating EHR data into clinical trial databases has been a goal of research institutions, industry and regulators. Such integration would reduce the burden of manual data entry, save time, decrease cost and accelerate clinical trials. The ongoing challenge has been exchanging data between healthcare systems and clinical trial systems, because each uses different technology platforms and data standards. In recent years, Fast Healthcare Interoperability Resources, or FHIR, a standard developed by the nonprofit organization Health Level Seven International (HL7), has been introduced as a secure and open solution for healthcare data exchange to accelerate information sharing. Most health apps use FHIR data standards, but FHIR has yet to be adopted for data exchange in industry-sponsored clinical trials. As one of the first health systems to implement FHIR, Ochsner has continuously explored opportunities to use the standards in other applications, including clinical trials. The Ochsner-Pfizer alliance project aims to build a model for applying FHIR standards so that high-quality clinical trial data may be collected consistently, reliably and securely within hospital and clinic electronic systems.

"We’re pleased that we succeeded in transferring core data types collected in healthcare provider electronic health records to Pfizer’s clinical trial data capture system using FHIR standards. To the best of our knowledge, this is a first for our industry," explains Rob Goodwin, Vice President, Operations Center of Excellence, Global Product Development at Pfizer. "There is more work ahead, but this is a significant step forward in simplifying data capture for clinical trials, and the first of many pioneering solutions we hope to develop through our partnership with Ochsner."

During the next phase, Pfizer and Ochsner will continue to develop new ways to digitize the patient and clinician experience in clinical trials, with attention to patient preferences on access to and use of their health data and with an overarching goal of enhancing the quality and value of clinical research interactions for all participants.

On February 19, 2019 Alkermes plc (Nasdaq: ALKS) and Clovis Oncology, Inc. (Nasdaq: CLVS) reported that the companies have entered into a research collaboration to evaluate ALKS 4230, Alkermes’ investigational engineered interleukin-2 (IL-2) variant immunotherapy, in combination with rucaparib, Clovis’ marketed PARP inhibitor, and lucitanib, Clovis’ investigational tyrosine kinase inhibitor (Press release, Clovis Oncology, FEB 19, 2019, View Source [SID1234533389]). The collaboration will explore the potential anti-cancer effects of both treatment combinations in preclinical models across multiple tumor types. Results of this research may form the basis for potential future clinical studies of the novel combinations of ALKS 4230 with rucaparib and/or lucitanib.

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"Our preclinical partnership with Clovis reflects our ongoing efforts to explore the numerous combination options afforded to ALKS 4230. The collaboration will allow us to examine combinations in two areas of keen interest, PARP and tyrosine kinase inhibition pathways," said Mark Namchuk , Ph.D., Senior Vice President, Research, Pharmaceutical and Non-Clinical Development at Alkermes. "Evidence of combined benefit of ALKS 4230 with rucaparib and/or lucitanib from these preclinical studies may provide a strong rationale to advance into clinical development."

"The unique profiles of rucaparib, lucitanib and ALKS 4230 may offer the potential for complementary therapies that could represent a meaningful opportunity for the development of new anti-cancer combination treatment options," said Patrick J. Mahaffy , President and CEO of Clovis Oncology . "We are committed to exploring combinations such as these with Alkermes in order to bring improved therapeutic outcomes to patients with multiple tumor types."

Under this collaboration agreement, Alkermes and Clovis will perform preclinical studies to examine the mechanism of action and efficacy of the combinations of ALKS 4230 with rucaparib and ALKS 4230 with lucitanib in multiple tumor models. Under the terms of the agreement, the companies will share costs related to the preclinical studies, and each will contribute their respective compounds to the research collaboration.

About ALKS 4230
ALKS 4230 is an investigational, novel, engineered fusion protein designed to selectively activate tumor-killing immune cells while avoiding the expansion of immunosuppressive cells by preferentially binding to the intermediate-affinity interleukin-2 (IL-2) receptor complex. The selectivity of ALKS 4230 is designed to leverage the proven anti-tumor effects of existing IL-2 therapy while mitigating certain limitations.

About Rucaparib
Rucaparib is an oral, small molecule inhibitor of the poly (ADP-ribose) polymerase (PARP) enzymes PARP-1, PARP-2, and PARP-3, which play a role in DNA repair. Rucaparib stimulates an anti-tumor immune response through the activation of the stimulator of interferon ( STING ) pathway and tumor cell death, resulting in the infiltration of multiple immune subsets including CD8 positive T-cells. 1

Rucaparib is being developed in multiple tumor types, including ovarian, metastatic castration-resistant prostate, and bladder cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway. Clovis holds worldwide rights for rucaparib. Rucaparib is an unlicensed medical product outside of the U.S. and Europe .

About Lucitanib
Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDFGRα/β) and fibroblast growth factor receptors 1 through 3 (FGFR1-3).

Emerging clinical data support the combination of angiogenesis inhibitors and immunotherapy to increase effectiveness in multiple cancer indications. 2 Angiogenic factors, such as vascular endothelial growth factor (VEGF), are frequently up-regulated in tumors and create an immunosuppressive tumor microenvironment. 3 Use of antiangiogenic drugs reverses this immunosuppression and can augment response to immunotherapy.