Sanofi (France), Medtronic, Inc. Team Up To Develop New Diabetes Devices Part I

Sanofi FR and Medtronic, Inc. MDT announced that they have signed a memorandum of understanding to enter into a global strategic alliance in diabetes, aimed at improving patient experience and outcomes for people with diabetes around the world. The alliance will initially focus on two key priorities: the development of drug-device combinations and delivery of care management services to improve adherence, simplify insulin treatment, and help people with diabetes better manage their condition.

The alliance will be structured as an open-innovation model, leveraging the capabilities, as well as the human and financial resources, of both companies. Based on the success of the two initial priorities, the companies may explore other areas for potential collaboration.

“We know that insulin and other medicines are only one element of treating the whole patient. There is no day off in managing diabetes, and lack of adherence is one of the major hurdles to optimal disease management. That is why Sanofi is committed to developing integrated care solutions that focus on making life easier for people with diabetes and improving clinical outcomes that may help reduce costs to the overall healthcare system,” commented Pascale Witz, Executive Vice President of Global Divisions & Strategic Development, Sanofi. “Through this important collaboration, Sanofi will tap into technology advances that aim to create holistic treatment solutions which take into account the individual patient’s needs.”

Bluebird bio Reports Rapid Transfusion Independence in Beta-Thalassemia Major Patients Treated with its LentiGlobin Product Candidate

bluebird bio, Inc., a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic and orphan diseases, today released initial positive clinical data from its HGB-205 clinical study of its LentiGlobin BB305 product candidate in beta-thalassemia major subjects at the 19th Annual Congress of the European Hematology Association (EHA) in Milan, Italy.

“We are gratified that the improvements we introduced into the BB305 lentiviral vector design and manufacturing process appear to have translated into clinical results that we believe support the potential for our LentiGlobin BB305 gene therapy to transform the lives of patients with beta-thalassemia major,” stated David Davidson, M.D., bluebird bio’s Chief Medical Officer. “We are encouraged by the early and high-level production of corrected betaAT87Q-globin and the rapid onset of transfusion independence in these initial subjects, as well as the absence of any gene therapy related adverse events. We look forward to providing additional data from this study and our ongoing multi-center Northstar Study later this year.”

The principal investigator of the HGB-205 Study, Marina Cavazzana, M.D delivered an oral presentation at the EHA Congress entitled “Improving gene therapy for beta-thalassemia major: initial results from Study HGB-205” on June 14, 2014 at 04:15 pm CET (10:15 am EDT). The presentation included data from the prior LG001 Clinical Study and the ongoing HGB-205 Study.

Summary of the clinical data presented at EHA were:

LG001 Clinical Study

* Clinical update provided on two subjects treated in the prior LG001 Study (subjects 3 and 4) using the prior lentiviral HPV569 product candidate

* Subject 3 remains blood transfusion independent 72 months after being transplanted with the lentiviral HPV569 product candidate

* Subjects 3 and 4 are producing 2.7 g/dL and 0.4 g/dL of therapeutic betaA-T87Q-globin post-transplant, respectively

* No drug product related adverse events were reported in the LG001 Study.

HGB-205 Clinical Study

* Clinical data were presented on two subjects (subjects 1 and 2), both with beta-thalassemia major and the Beta E/Beta 0 genotype who were treated using the new lentiviral vector BB305

* At 4.5 months following autologous transplant subject 1 had a total hemoglobin of 10.1 g/dL of which 6.6 g/dL was therapeutic betaAT87Q-globin, and at 2 months post-transplant subject 2 had a total hemoglobin of 11.6 g/dL of which 4.2 g/dL was betaAT87Q-globin

* Subjects 1 and 2 received their last blood transfusion on day 10 and 12, respectively, post-transplant and both subjects remain blood transfusion independent

* Vector copy number in the drug product for subjects 1 and 2 were 1.5 and 2.1, respectively; multiple times higher than the drug product vector copy numbers reported in the prior LG001 Study (VCN 0.6 and 0.3 for Subjects 3 and 4, respectively)

* No drug product related adverse events were reported, and the integration site analysis performed on subject 1 at the 3-month time point showed polyclonal reconstitution.

We anticipate reporting additional data from the HGB-205 Study and from our ongoing Northstar Study in late 2014.

Pfizer Opens New State-of-the-Art Research and Development Site in Cambridge, Massachusetts part II

“We are thrilled to welcome Pfizer’s new R&D hub to the Kendall Square innovation district,” said MIT President L. Rafael Reif, Ph.D. “We could not ask for a more exciting tenant for these spaces. MIT and Pfizer have established a tradition of working together to advance science, research and education, through strategic initiatives like MIT’s Synthetic Biology Center. With this extraordinary core of Pfizer research teams now right next door to our labs at MIT, we can capitalize on the power of proximity to speed progress towards solutions to urgent challenges in human health.”

“Pfizer’s new research facilities are an important addition to the rich concentration of biomedical organizations in Kendall Square,” said Massachusetts Governor Deval Patrick. “The opening of the hub demonstrates Pfizer’s commitment to innovation and builds on the more than 15 years that Pfizer has been a part of the life sciences community here in Massachusetts.”

In addition to the new Cambridge R&D hub, Massachusetts is home to Pfizer’s research and manufacturing site in Andover and is the global headquarters for Pfizer’s Centers for Therapeutic Innovation (CTI) in Boston. By establishing collaborations with institutions working on novel and cutting-edge research, CTI’s model is designed to build an innovative network for drug discovery, with the goal of bringing new, targeted therapies to patients quickly.

Pfizer Opens New State-of-the-Art Research and Development Site in Cambridge, Massachusetts part I

Pfizer Inc. announced today the opening of a new 280,000 square-foot Research and Development (R&D) hub in Cambridge, Mass. The new Pfizer facilities in Kendall Square bring together 1,000 colleagues from three area locations and position Pfizer in closer proximity to leading academic institutions, hospitals and patient organizations.

“Our new Kendall Square presence in Cambridge represents an important milestone in Pfizer’s approach to creating a sustainable R&D engine that is designed to yield a flow of innovative therapies year after year,” said Mikael Dolsten, M.D., Ph.D., President of Worldwide Research and Development at Pfizer. “Having all of our Cambridge-area researchers working closely together in one of the world’s most exciting biomedical ecosystems will allow us to continue our efforts to grow our external collaborations and has the potential to help speed the translation of scientific knowledge into potential medical breakthroughs across areas of unmet need such as lupus, inflammatory bowel disease, kidney disease, type 2 diabetes, muscular dystrophy and Parkinson’s disease.”

Led by Pfizer Group Vice President of BioTherapeutics R&D, José-Carlos Gutiérrez-Ramos, Ph.D, the new laboratory facilities, located in the heart of Kendall Square at 610 and 700 Main Street, respectively, are leased from the Massachusetts Institute of Technology (MIT). Pfizer scientists will work in state-of-the-art lab space on a range of clinical programs across several therapeutic areas, including inflammation, immunology, rare disease, cardiovascular and metabolic diseases, and neuroscience.

Oncomed Pharmaceuticals Voluntarily Halts Enrollment and Dosing in Phase 1 Vantictumab and Fzd8-Fc Trials

OncoMed Pharmaceuticals Inc., announced that the company has voluntarily halted patient enrollment and dosing in its ongoing Phase 1 clinical trials of its two Wnt pathway inhibitor programs, vantictumab (anti-Fzd7, OMP-18R5) and Fzd8-Fc (OMP-54F28).

OncoMed has been informed by the participating clinical sites of recent on-target mild-to-moderate bone-related adverse events for the two programs. To date, bone-related adverse events have been observed in 8 of 63 (13%) patients treated with vantictumab and 2 of 41 (5%) patients treated with Fzd8-Fc. After careful analysis of the recent mild-to-moderate adverse event incidents, OncoMed has halted enrollment and dosing in the Phase 1 studies for both programs as a precautionary measure. OncoMed, in conjunction with its academic bone expert advisors and study investigators, continues to analyze the clinical data in order to submit amended protocols to the U.S. Food and Drug Administration (FDA) and subsequently to the clinical study sites.

The amendments for the Phase 1b combination trials will include 1) modified dosing regimens, such as lower and less frequent dosing, 2) updated risk mitigation measures, such as increased monitoring and bone protection strategies, and 3) modified enrollment criteria. Enrollment and dosing of new patients is expected to resume once amendments go through the process of review by the FDA and approval by the study sites’ institutional review boards (IRBs).

In parallel, the company intends to continue existing or modified dosing of those patients in the completed single-agent Phase 1a clinical trials for both vantictumab and Fzd8-Fc who have remained on treatment with the investigational agent for extended periods of time without disease progression and without significant drug-related adverse events. OncoMed has notified the FDA of these actions.

Breakthrough: AFFiRiS AG Claims A First In Alzheimer’s Disease Therapy Part II

Significant Impact 

Commenting on these results Dr. Walter Schmidt, CEO and Co-founder of AFFiRiS AG, states: “Our results demonstrate that AD04 is the first drug ever to show disease modifying properties in Alzheimer’s patients. This success is owed to our strategy of clinical maturation, which in the case of Alzheimer’s has so far moved forward four different product candidates namely AD01 – AD04 into clinical development.”

Dr. Frank Mattner, CSO and Co-founder, adds: “Both compounds applied in this trail, AD02 and AD04, showed excellent safety profiles. Top compound AD02 performed very well in stabilization of cognitive functions in a dose dependent manner. 24-31 % of treated patients showed stabilization of clinical progression. However, AD04 turned out to be superior to AD02 as 47% of the patients stabilized regarding their cognitive/functional status. On top of this, this effect was statistically significantly correlated with the rescue of the hippocampus, the region of the human brain, where cognitive and memory functions are located (p=0.0016). This correlation of significant clinical and biomarker effects meets EMA’s and FDA’s definition of disease modification in the context of a compound with a consistent mode of action. Therefore, we decided to have a strong focus on AD04 for further clinical development. Our strategy of clinical maturation allows for an efficient progress during clinical development. By doing so, it reduces financial risks associated with any clinical trial.” In fact, the clinical maturation strategy has been established by AFFiRiS and is based on parallel clinical testing of several drug candidates against a certain disease to ensure that the best therapy for humans will be developed.

Prof. AchimSchneeberger, Chief Medical Officer at AFFiRiS, extends: “From the beginning we were running our Alzheimer’s therapy program with several drug candidates. AD04 now shows the most convincing therapeutic benefits including an effect on NPI and quality of life, which are relevant to patients and their caregivers. Because the current results are so extremely positive and consistent across clinical outcomes and brain volumes we expect to verify them in further clinical investigations.”

Profitable Programs

In addition to it’s Alzheimer’s therapy program AFFiRiS’ pipeline contains product candidates against Parkinson’s, Atherosclerosis, Diabetes and several other conditions. Dr. Mattner comments: “AFFiRiS focuses on the development of drugs against conditions with urgent requirement for new treatments and attractive market volumes. Our Alzheimer’s and our Parkinson’s developments are successful examples of this. Indeed AFFiRiS was the first company world-wide that started clinical testing of Parkinson’s drugs with the potential for disease modification. Eagerly awaited results of this clinical trial will be released within the next two months.”




Breakthrough: AFFiRiS AG Claims A First In Alzheimer’s Disease Therapy Part I

AFFiRiS announced today the results of a phase II study in Alzheimer patients. AFFiRiS’ proprietary compound AD04 is the first drug ever to demonstrate clinical and biomarker effects consistent with disease modification in Alzheimer patients. Upon treatment with AD04, effects consistent with disease modification were achieved for at least 18 months in 47% of treated patients. This beneficial effect was dose dependent and more effective in early disease patients. Furthermore, prevention of hippocampal decline was correlated with the beneficial impact on clinical progression and was statistically significant. Therefore, these results for the very first time meet all of the criteria for disease modification as defined by US and European Regulatory Agencies FDA (Food and Drug administration) and EMA (European Medicines Agency).

AFFiRiS AG of Vienna, Austria, today released for the first time results of a clinical phase II study in Alzheimer patients of its proprietary compound AD04, a therapeutic drug against Alzheimer’s disease. The results show an impressive therapeutic effect of AD04 and make it the first ever compound demonstrating clinical and biomarker evidence consistent with disease modification of Alzheimer’s disease. A statistically significant correlation was demonstrated between the cognitive/functional outcome and the volume of the hippocampus, the region of the brain locating the cognitive/memory functions, both of which demonstrated positive impact on disease progression over 18 months. Similar stabilization was also seen across behavioral and quality of life outcomes.

There was also a stabilization of the cognitive/functional endpoint found in those patients of this study who were treated with AD02, so far the company’s lead compound in AD. Dependent on dosage and formulation of AD02 in three different study arms, 24-31 % of the patients showed cognitive/functional stabilization or improvement. However, statistically significant correlation with biomarker Hippocampus volume could not be demonstrated within the observation period of 18 months. Altogether 332 patients were treated in an international multi-centric clinical trial into five different study arms, and over 85% completed the study.

Bladder Cancer Med Anti-PDL1 (MPDL3280A) from GenetechNabs Breakthrough Status Part II

Full results of the study will be presented today at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) by Thomas Powles, M.D., clinical professor of Genitourinary Oncology, Barts Cancer Institute at the Queen Mary University of London, United Kingdom (Abstract #5011, Saturday, May 31, 3:36–3:48 p.m. CDT).

About the Phase I MPDL3280A Study

* The Phase I study is a single-arm, multi-center, open-label trial with a cohort of 68 people with previously treated, metastatic bladder cancer.

* The study included 30 patients who were identified as PD-L1 positive (immunohistochemistry [IHC] 2/3) using an investigational PD-L1 diagnostic test being developed by Roche.

* After six weeks of follow-up, the objective response rate (ORR) as measured by RECIST criteria was 43 percent (13/30), and after 12 weeks, ORR was 52 percent (13/25) in people with PD-L1-positive tumors.

– A complete response (no radiographic evidence of tumor) was observed in 7 percent of PD-L1-positive people (2/30).

– The ORR was 11 percent (4/35) in people whose tumors were identified as PD-L1-negative (IHC 0/1) by our investigational test.

– People in the study experienced a median time to response of 42 days.

* Treatment-related Grade 3 AEs occurred in 4 percent (3/68) of people in the study and included weakness (asthenia; 2 percent), low platelet count (thrombocytopenia; 2 percent) and low phosphate levels (blood phosphorus decrease; 2 percent).

* The most common AEs observed to date occurring in more than 5 percent of people in the study were decreased appetite (12 percent), fatigue (12 percent), nausea (12 percent), fever (pyrexia; 9 percent) and weakness (asthenia; 7 percent).

About MPDL3280A (anti-PDL1)

MPDL3280A (also known as anti-PDL1) is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. MPDL3280A is designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, MPDL3280A may enable the activation of T cells, restoring their ability to effectively detect and attack tumor cells.

About Bladder Cancer

Metastatic urothelial bladder cancer is associated with a poor prognosis and limited treatment options. According to the American Cancer Society (ACS), it is estimated that more than 74,000 Americans will be diagnosed with bladder cancer in 2014, and approximately 15,000 of new diagnoses are made when bladder cancer is in advanced stages. There is a dramatic difference in survival rates between early and advanced bladder cancer. The ACS estimates that approximately 15 percent of people with advanced bladder cancer (stage IV) will live for five years, compared to 88 percent when diagnosed during stage I. Men are about three to four times more likely to get bladder cancer during their lifetime than women.

A new era for chronic lymphocytic leukemia PART1

The FDA has approved ofatumumab (Arzerra) plus chlorambucil for previously untreated patients with chronic lymphocytic leukemia (CLL). In the trial, the combination of the anti-CD20 monoclonal antibody ofatumumab and chlorambucil demonstrated a 9.3-month improvement in PFS compared with chlorambucil alone. The approval comes following a Breakthrough Therapy designation for the drug The FDA first approved ofatumumab in 2009 for the treatment of patients with CLL who no longer respond to chemotherapy. This approval by the FDA for the use of Arzerra in the first-line setting means that appropriate patients with CLL have a new treatment option.

I am pleased that Arzerra has been shown to provide clinical benefit and will now be available in the first-line setting. Arzerra, the first approved therapeutic created by Genmab and developed in collaboration with GSK, is the only therapeutic CD20 antibody approved in combination with chlorambucil for first-line CLL and as a monotherapy for CLL refractory to fludarabine and alemtuzumab. Ofatumumab targets CD20 similarly to the well-established treatment rituximab. Targeting CD20 on the surface of both normal and malignant B-cells induces cell death through antibody-dependent cell-mediated toxicity, complement-dependent cytotoxicity, and apoptosis.

Ongoing studies are exploring ofatumumab as a treatment for patients with CLL. In the phase III study, ofatumumab was compared with ibrutinib in  patients with relapsed or refractory CLL or small lymphocytic leukemia. This study was stopped early after demonstrating a significant improvement in the primary endpoint of PFS and the secondary endpoint of overall survival for patients treated with ibrutinib compared with ofatumumab.Based on these results, a supplemental New Drug Application was submitted for ibrutinib in April 2014.

CD19,a new target for antibody-based therapies

For the past two decades, researchers have been exploring B-cell specific antigens in hopes of developing a new anticancer target that would mirror the success of the CD20-targeting rituximab (Rituxan). Nowstrategies aimed at CD19 are proving particularly promising.

CD19 is serving as the target not only of antibody-based therapies but also in a potentially paradigm-altering approach to cancer immunotherapy that continues to yield impressive clinical outcomes. The complexities of developing CD19-targeting immunotherapy were highlighted recently when several clinical trials were suspended for a safety review in response to the deaths of two patients during a study.

CD19 plays a critical role in establishing an optimal immune response by regulating both B-cell receptor (BCR)- dependent and BCR–independent signaling pathways. It regulates both antigen-independent development and immunoglobulin- induced activation of B cells. CD19 makes an attractive target for cancer therapy since its expression on normal cells is limited to those of B-cell lineage. Furthermore, it is expressed on the vast majority of B-cell malignancies, including acute lymphoblastic leukemias (ALLs), B-cell lymphomas, B-cell leukemias.

CD19 is a suitable tumor-associated antigen (TAA) against which to target anticancer agents. In contrast to CD20, CD19 is expressed throughout B-cell development, from B-cell precursors through to mature B cells, before expression is lost when they become plasma cells. This wider range of expression potentially gives CD19-targeted agents an advantage over their CD20 counterparts, since they could be more useful in treating early B-cell neoplasms like ALL, which cannot be treated with rituximab.