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CTI BioPharma And Baxter Announce Patient-Reported Outcomes (PROs) From Pacritinib Phase 3 In Patients With Myelofibrosis To Be Presented In Late-Breaking Session At EHA

On June 10, 2015 CTI BioPharma and Baxter International reported that Patient Reported Outcomes (PROs) data from the Phase 3 PERSIST-1 trial, evaluating pacritinib in patients with myelofibrosis, will be highlighted in a late-breaking oral presentation at the upcoming 20th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), June 11-14, Vienna (Press release, CTI BioPharma, JUN 10, 2015, View Source;p=RssLanding&cat=news&id=2057957 [SID:1234505406]). Pacritinib is an investigational oral multikinase inhibitor with specificity for JAK2 and FLT3. These data were also selected for inclusion in the official EHA (Free EHA Whitepaper) Press Briefing on Friday, June 12, 2015 at 08:30 CEST.

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Myelofibrosis is associated with significantly reduced quality of life and shortened survival. As the disease progresses, the body slows production of important blood cells and within one year of diagnosis the incidence of disease-related thrombocytopenia (very low blood platelet counts), severe anemia, and red blood cell transfusion requirements increase significantly. Among other complications, most patients with myelofibrosis present with enlarged spleens (splenomegaly) as well as many other potentially devastating physical symptoms such as: abdominal discomfort, bone pain, feeling full after eating little, severe itching, night sweats, and tiredness.

Full details for the abstracts involving pacritinib in this year’s EHA (Free EHA Whitepaper) program are below:

Title: Patient-Reported Outcomes (PROS) in PERSIST-1: A Randomized, Multi-Country Phase III Trial of the JAK2 Inhibitor Pacritinib (PAC) VS. Best Available Therapy (BAT) in Myelofibrosis (MF)
First Author: Ruben Mesa, M.D., Deputy Director, Mayo Clinic Cancer Center, Chair of the Division of Hematology & Medical Oncology, Mayo Clinic Cancer Center, Scottsdale, AZ and one of the principal investigators for PERSIST-1
Date/Time: Sunday, June 14 at 12:15 CEST
Location: Room A7
Presentation Type: Oral Presentation
Abstract #: LB2072
This abstract is under a press embargo until Friday, June 12 at 09:30 CEST.

Title: PERSIST-1: A Phase III Study of Pacritinib (PAC) vs Best Available Therapy (BAT) in Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (PPV-MF) or Post-Essential Thrombocythemia MF (PET-MF)
First Author: Claire Harrison, M.D., Consultant Hematologist, Guy’s and St. Thomas’ NHS Foundation Trust, Guy’s Hospital, London, United Kingdom and one of the principal investigators for PERSIST-1
Date/Time: Friday, June 12 at 17:15 to 18:45 CEST
Location: Poster area (Hall C)
Presentation Type: Poster
Abstract #: LB314
The full abstract can be viewed here.

About Pacritinib

Pacritinib is an oral multikinase inhibitor with specificity for JAK2 and FLT3. The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia, and lymphoma. The kinase profile of pacritinib suggests its potential therapeutic utility in conditions such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and chronic lymphocytic leukemia (CLL) due to its potent inhibition of c-fms, IRAK1, JAK2, and FLT3.1

Cellectis Announces Promising Study on Next Generation Engineered Allogeneic CAR T-cells

On June 10, 2015 Cellectis reported the publication of a study in Molecular Therapy, a Nature Publishing Group Journal, describing the development of the next generation of engineered CAR T-cells compatible with allogeneic adoptive transfer immunotherapy (Press release, Cellectis, JUN 10, 2015, View Source [SID:1234505394]).

Study Highlights

• The adoptive transfer of allogeneic CAR T-cells represents a promising strategy to fight multiple cancers worldwide.

• Cellectis has streamlined an engineering process to generate CAR T-cells that could be compatible with allogeneic adoptive transfer in combination with nucleoside analogues lymphodepleting drugs.

When allogeneic CAR T-cell infusion is considered, host versus graft and graft versus host reactions must be avoided to prevent rejection of adoptively transferred cells, host tissue damages and to elicit significant antitumoral outcome. In this report, Julien Valton Ph.D. and his collaborators addressed these requirements by developing a multidrug resistant TCRαβ-deficient CAR T-cell. This engineered T-cell displayed efficient antitumor activity and significant resistance to purine and pyrimidine nucleoside analogues, which are currently used clinically in preconditioning lymphodepleting regimens. Their properties could prevent their alloreactivity and enable control over engraftment in patients. In addition, they are compatible in combination therapy, an approach likely to improve clinical outcomes. By providing a basic framework to develop a universal T-cell compatible with allogeneic adoptive transfer, Cellectis is laying the foundation for the large-scale utilization of CAR T-cell immunotherapies.

Julien Valton, Ph.D. Innovation Senior Scientist

Dr. Julien Valton obtained his Ph.D. degree at Université Joseph Fourier in Grenoble (France) where he was trained as enzymologist. He then joined the Yale School of Medicine to apply his knowledge to therapeutic research, by investigating the mechanism of inhibition of receptor tyrosine kinases involved in the development of gastrointestinal cancer. In 2009, he moved a step further into the field of applied science by joining the R&D Department of Cellectis, where he actively participated to set, improve and use meganucleases and TALEN for targeted gene therapy and genome engineering purposes. He is now part of the NYC based Cellectis, Inc.

A Multidrug Resistant Engineered CAR T-Cell for Allogeneic Combination Immunotherapy

Julien Valton, Valérie Guyot, Alan Marechal, Jean Marie Filhol, Alexandre Juillerat, Aymeric Duclert, Philippe Duchateau and Laurent Poiro

Agios Pharmaceuticals Announces FDA Orphan Drug Designation Granted to AG-120 for Treatment of IDH1-Mutant Positive Acute Myelogenous Leukemia

On June 10, 2015 Agios Pharmaceuticals reported that the U.S. Food and Drug Administration (FDA) has granted the company orphan drug designation for AG-120 for treatment of patients with acute myelogenous leukemia (AML) (Press release, Agios Pharmaceuticals, JUN 10, 2015, View Source;p=RssLanding&cat=news&id=2058334 [SID:1234505391]). AG-120 is an oral, first-in-class IDH1 mutant inhibitor being evaluated in a Phase 1 clinical trial in patients with advanced hematologic malignancies that carry an IDH1 mutation.

The FDA’s Office of Orphan Drug Products grants orphan status to support development of medicines for underserved patient populations, or rare disorders, that affect fewer than 200,000 people in the U.S. Orphan drug designation provides to Agios certain benefits, including market exclusivity upon regulatory approval if received, exemption of FDA application fees and tax credits for qualified clinical trials.

"Receiving orphan drug designation for AG-120 is an important milestone as we continue to move this program to late-stage development," said Chris Bowden, M.D. chief medical officer of Agios. "We are pleased with the progress we are making in the clinic and look forward to presenting new data from our ongoing Phase 1 study of AG-120 at the Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) later this week. We believe that AG-120, which is on track to initiate multiple expansion cohorts in the next month, has the potential to play a significant role in shifting the treatment paradigm for IDH1-mutant positive hematologic cancers from the conventional chemotherapy approach."

AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia in adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and according to the American Cancer Society the median age is 66. Less than 10 percent of U.S. patients are eligible for bone marrow transplant, and the vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 20 to 25 percent. IDH1 mutations are present in about 6 to 10 percent of AML cases.

FDA Agrees with OncoGenex’ Phase 3 AFFINITY Protocol Amendment

On June 10, 2015 OncoGenex Pharmaceuticals reported that the U.S. Food and Drug Administration (FDA) has agreed to the Company’s proposed amendment to the Phase 3 AFFINITY protocol and statistical analysis plan (Press release, OncoGenex Pharmaceuticals, JUN 10, 2015, View Source [SID:1234505390]). The amendment includes the addition of a co-primary endpoint designed to prospectively evaluate the survival benefit of custirsen in men who are at increased risk for poor outcomes when treated with cabazitaxel for metastatic castrate-resistant prostate cancer (CRPC).

"There are limited effective treatment options for men with metastatic CRPC who have risk factors for poor outcomes and who fall into a poor prognosis category. Recent findings from the SYNERGY trial showed a significant survival benefit in this group of patients," said Cindy Jacobs, PhD, MD, Chief Medical Officer and Executive Vice President of OncoGenex. "We have applied this key insight from the SYNERGY trial to the AFFINITY protocol to better evaluate this vulnerable subpopulation of men who have poor prognosis and shorter survival time."

The FDA is in agreement with plans for prospectively defining a poor prognostic subpopulation in the Phase 3 AFFINITY trial. OncoGenex, in collaboration with study investigators, has defined a simple 5-criteria characterization for poor prognosis in prostate cancer based on the Phase 3 SYNERGY trial, which includes: poor performance status, elevated prostate specific antigen (PSA), elevated lactate dehyrdogenase (LDH), decreased hemoglobin, and the presence of liver metastasis. Patients with poor prognosis will be identified as having 2 or more of these 5 well-recognized high-risk criteria. The proposed change for AFFINITY is also consistent with custirsen’s mechanism of action, since custirsen was designed to address treatment resistance which may be more prevalent in this subpopulation.

In the revised statistical analysis plan for the AFFINITY trial, the hypothesized hazard ratio (HR) for the poor prognosis subpopulation is specified to be 0.69 with the critical HR ≤ 0.778. The hypothesized HR for the intent-to-treat patients (ITT population) remains unchanged as 0.75 with the critical HR ≤ 0.820.

Timing for the final analysis of the poor prognosis subpopulation is projected to occur by the end of 2015, while the final analysis for the ITT population is projected to occur in the second half of 2016. FDA and OncoGenex have further agreed that an interim analysis will occur for the ITT population when the final analysis for the poor prognosis subpopulation occurs. This interim analysis will have both futility and early efficacy criteria defined for the ITT population. If the earlier final analysis on the poor prognostic subpopulation shows a survival benefit for custirsen, OncoGenex could initiate a regulatory submission. The entire trial could also be stopped early due to efficacy based on the interim assessment for the ITT population by the Independent Data Monitoring Committee (IDMC).

"Findings from the SYNERGY trial recently presented at ASCO (Free ASCO Whitepaper) have provided important insight into the patient population in whom custirsen treatment is most relevant," said Scott Cormack, President and CEO of OncoGenex. "We are pleased that the FDA has agreed with our amendment and look forward to announcing top-line results at the end of this year and in 2016."

OncoGenex has also initiated a review with the European Medicines Agency (EMA) for the proposed amendment to the Phase 3 AFFINITY protocol and statistical analysis plan, and expects to have this completed in the second half of 2015.

A retrospective analysis of data from the Phase 3 SYNERGY trial recently presented at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) showed a benefit with custirsen therapy when added to first-line docetaxel chemotherapy in men with metastatic CRPC who had a poor prognosis. The analysis showed that over 40 percent of men in the trial had at least 2 of the 5 common risk factors for poor prognosis as stated above. In these men, the analysis found a 27 percent lower risk of death when custirsen was used in combination with first-line docetaxel compared to docetaxel alone.

AFFINITY is being conducted at 95 global clinical trial sites and earlier this year, the IDMC recommended the trial continue following the completion of an interim futility analysis. The trial is fully accrued, and the protocol amendment does not affect the conduct of the study.

DelMar Pharmaceuticals to Present at the BIO International Convention on June 17, 2015

On June 10, 2015 DelMar Pharmaceuticals reported that it will be presenting at the BIO International Convention being held June 15-18, 2015, in Philadelphia, PA (Press release, DelMar Pharmaceuticals, JUN 10, 2015, View Source [SID:1234505389]).

Jeffrey Bacha, DelMar’s president and CEO, will present on Wednesday, June 17, 2015, at 10:15 a.m. EDT, in Theater 4 of the Pennsylvania Convention Center. Mr. Bacha will provide an update on the Company’s drug development programs with its lead product candidate VAL-083 (dianhydrogalactitol), including DelMar’s ongoing Phase 1/2 trial in refractory glioblastoma multiforme (GBM), the most common and deadly form of brain cancer, and upcoming clinical development plans in non-small cell lung cancer (NSCLC).

About the BIO International Convention

The BIO International Convention is considered one of the world’s largest, most influential biotech meetings and regularly attracts 15,000 of the most powerful biotech and pharma players from 65 countries, offering powerful business partnering, networking and education that go far beyond professional development. DelMar management will be available during the conference for meetings with potential drug development and commercialization partners from the biopharmaceutical industry. For more information, please visit View Source

About VAL-083

VAL-083 is a "first-in-class", small-molecule chemotherapeutic. In more than 40 Phase 1 and 2 clinical studies sponsored by the U.S. National Cancer Institutes, VAL-083 demonstrated safety and efficacy in treating a number of cancers including lung, brain, cervical, ovarian tumors and leukemia. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia and lung cancer and has received orphan drug designation in Europe and the U.S. for the treatment of gliomas.

As a potential treatment for glioblastoma, VAL-083’s mechanism of action appears to be unaffected by the expression of MGMT, a DNA repair enzyme that causes chemotherapy resistance to front-line treatment with Temodar (temozolomide).

DelMar is currently studying VAL-083 in a multi-center Phase I/II clinical trial for patients with refractory glioblastoma multiforme (GBM) in accordance with the protocol that has been filed with the U.S. Food and Drug Administration (FDA). Eligible GBM patients must have failed both Avastin (bevacizumab) and Temodar (temozolomide) unless either of these therapies was contraindicated. (ClinicalTrials.gov Identifier NCT01478178).

The four current sites for the VAL-083 clinical trial include: The University of California, San Francisco (UCSF); The Mayo Clinic, Rochester MN; The Sarah Cannon Cancer Research Institute (SCRI), Nashville TN; and the SCRI affiliate site at Florida Cancer Specialists in Sarasota FL. DelMar anticipates opening additional clinical sites as the trial progresses. Further information on this clinical trial can be found on the company’s website at www.delmarpharma.com.