On November 5, 2015 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported business and financial highlights for the third quarter ended September 30, 2015 (Press release, Celldex Therapeutics, NOV 5, 2015, View Source [SID:1234508026]).

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"Celldex continues to advance one of the most robust, well-staged pipelines in immuno-oncology," said Anthony Marucci, President and Chief Executive Officer of Celldex Therapeutics. "As we move closer to final data from the ACT IV study in newly diagnosed glioblastoma, we continue to build on the potential promise of RINTEGA in the recurrent setting and look forward to presenting long-term survival data from the ReACT study at the SNO meeting later this month. In the third quarter we continued to execute on all fronts, including enrolling patients to seven ongoing Celldex-sponsored clinical trials. In addition, there are now numerous investigator initiated studies ongoing with additional concepts under discussion. We look forward to data in 2016 from several of these studies that we believe will further support the critical role of immunotherapy in oncology."

Program Updates:

RINTEGA ("rindopepimut"; "rindo"; CDX-110), an EGFRvIII(v3)-specific therapeutic vaccine for glioblastoma (GBM)

The ACT IV study is a randomized, double-blind, placebo controlled study of RINTEGA plus GM-CSF added to standard of care temozolomide in patients with newly diagnosed, surgically resected, EGFRvIII-positive glioblastoma. 745 patients were enrolled into ACT IV to reach the required 374 patients with minimal residual disease (assessed by central review) needed for analysis of the primary overall survival endpoint. All patients, including those with disease that exceed this threshold, will be included in a secondary analysis of overall survival as well as analyses of progression-free survival, safety and tolerability, and quality of life. The study design includes interim analyses conducted by an independent Data Safety and Monitoring Board (DSMB) at 50 and 75% of events (deaths). The first interim analysis occurred in June 2015, and the DSMB recommended continuation of the study as planned. The Company anticipates that the study will reach the required number of events to perform the second interim analysis in late 2015 and that the analysis will occur in early 2016.

As previously reported, data from the Phase 2 ReACT study in patients with recurrent glioblastoma were presented in an oral session at the 2015 ASCO (Free ASCO Whitepaper) Annual Meeting by David A. Reardon, M.D., Clinical Director, Center for Neuro-Oncology, Dana-Farber Cancer Institute and Associate Professor of Medicine, Harvard Medical School, and the lead investigator of the ReACT study. Patients on the RINTEGA arm experienced a statistically significant overall survival (OS) benefit, and an impressive, emerging long-term survival benefit was observed. The primary endpoint of the study, progression-free survival at six months (PFS6), was met, and a clear advantage was demonstrated across multiple, clinically important endpoints including long-term progression-free survival, objective response rate (ORR) and need for steroids. The Company will present an update on overall survival and long-term survival in a podium presentation at the 20th Annual Scientific Meeting of the Society for Neuro-Oncology (SNO) on Friday, November 20th at 1:30 PM CT/2:30 PM ET.

Glembatumumab vedotin ("glemba"; CDX-011), an antibody-drug conjugate targeting gpNMB in multiple cancers

Enrollment continues in the Company’s Phase 2b randomized study (METRIC) of glembatumumab vedotin in patients with metastatic triple negative breast cancers that overexpress gpNMB, a molecule associated with poor outcomes for triple negative breast cancer patients and the target of glembatumumab vedotin. Enrollment is open across the United States, Canada and Australia. Trial expansion into the European Union (EU) is underway, and the Company plans to open enrollment in up to 50 sites in the EU in early 2016. Based on current projections, enrollment will be completed in the second half of 2016.

Patient enrollment continues in the Phase 2 study of glembatumumab vedotin in metastatic melanoma.

Celldex continues to advance plans to expand the study of glembatumumab vedotin in other cancers in which gpNMB is expressed.
A Phase 2 study in squamous cell lung cancer is expected to commence in Q1 2016.
Celldex and the National Cancer Institute have entered into a Cooperative Research and Development Agreement (CRADA) under which the NCI will sponsor two studies of glembatumumab vedotin—one in uveal melanoma and one in pediatric osteosarcoma.
Varlilumab ("varli"; CDX-1127), a fully human monoclonal agonist antibody that binds and activates CD27, a critical co-stimulatory molecule in the immune activation cascade

The Phase 1/2 study of varlilumab and nivolumab (Opdivo) in adult patients with advanced non-small cell lung cancer, metastatic melanoma, colorectal cancer, ovarian cancer, and head and neck squamous cell carcinoma is actively enrolling patients. This study is being conducted by Celldex under a clinical trial collaboration with Bristol-Myers Squibb. The companies are sharing development costs.

In April 2015, Celldex announced that it had entered into a clinical trial collaboration with Roche to evaluate the combination of varlilumab and atezolizumab (anti-PDL1) in a Phase 1/2 study in renal cell carcinoma. Under the terms of this agreement, Roche will provide study drug, and Celldex will be responsible for conducting and funding the study, which is expected to open to enrollment in Q4 2015.

Additional combination studies of varlilumab continue to enroll patients including:
A Phase 1/2 safety and tolerability study examining the combination of varlilumab and sunitinib (Sutent) in patients with metastatic clear cell renal cell carcinoma (CC-RCC); and,
A Phase 1/2 safety and tolerability study examining the combination of varlilumab and ipilimumab (Yervoy) in patients with Stage III or IV metastatic melanoma. In the Phase 2 portion of the study, patients with tumors that express NY-ESO-1 will also receive Celldex’s CDX-1401.

Celldex will present a preclinical poster on the contribution of varlilumab’s immune stimulating properties versus regulatory T cell (Treg) depletion in multiple tumor models on Friday, November 6, 2015 at 6:15 PM ET at the 2015 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting.

Oncothyreon recently completed evaluation of two dosing cohorts in the Oncothyreon-led Phase 1b trial of ONT-10, a therapeutic vaccine targeting the tumor-associated antigen MUC1, in combination with varlilumab in patients with advanced breast and ovarian cancers. Preliminary data from these two cohorts did not demonstrate sufficient activity to move forward with the program, and Oncothyreon does not plan to enroll additional patients in the Phase 1b trial. Varlilumab biomarker analyses from peripheral blood samples from this study are consistent with prior experience including an increase in activated T cells and natural killer cells and a decrease in regulatory T cells.

Patient treatment in the Phase 1 dose-escalation study of varlilumab is complete. Any incremental data updates will be included in a future scientific presentation/publication.

Efforts are underway for additional Phase 2 studies of varlilumab, and the Company will provide updates on these studies as they are initiated.
CDX-1401, an antibody-based NY-ESO-1-specific therapeutic vaccine for multiple solid tumors

A Phase 1/2 study examining the combination of varlilumab and ipilimumab (Yervoy) continues to enroll patients with Stage III or IV metastatic melanoma. In the Phase 2 portion of the study, patients with tumors that express NY-ESO-1 will also receive CDX-1401, an off-the-shelf antibody-based dendritic cell targeted vaccine.

Celldex continues to support several external collaborations, including a National Cancer Institute sponsored Phase 2 study of CDX-1401 and CDX-301 for patients with metastatic melanoma, which recently completed enrollment.
CDX-301 (recombinant human Flt3L), a potent hematopoietic cytokine that uniquely expands dendritic cells and hematopoietic stem cells

CDX-301 is being developed as a combination product with other immuno-oncology agents in investigator-sponsored studies.

A pilot study of CDX-301 alone and in combination with Mozobil in hematopoietic stem cell transplantation was initiated in September 2014 and is currently enrolling patients and sibling-matched donors. The Company anticipates presenting early data from this study in Q1 2016.
Third Quarter and First Nine Months 2015 Financial Highlights and 2015 Guidance

Cash position: Cash, cash equivalents and marketable securities as of September 30, 2015 were $304.6 million compared to $334.0 million as of June 30, 2015. The decrease of $29.4 million was primarily driven by our third quarter net cash used in operating activities of $27.8 million. As of September 30, 2015 Celldex had 98.6 million shares outstanding.

Revenues: Total revenue was $1.0 million in the third quarter of 2015 and $3.7 million for the nine months ended September 30, 2015, compared to $1.1 million and $2.1 million for the comparable periods in 2014. The increase in the nine months ended September 30, 2015 was primarily due to our clinical trial collaboration with Bristol-Myers Squibb and our research and development agreement with Rockefeller University.

R&D Expenses: Research and development (R&D) expenses were $24.7 million in the third quarter of 2015 and $76.3 million for the nine months ended September 30, 2015, compared to $26.2 million and $77.4 million for the comparable periods in 2014.

G&A Expenses: General and administrative (G&A) expenses were $8.5 million in the third quarter of 2015 and $22.8 million for the nine months ended September 30, 2015, compared to $5.0 million and $14.4 million for the comparable periods in 2014. The increase in G&A expenses was primarily attributable to higher personnel-related expenses as we prepare for potential product launches and a $3.3 million increase year to date in RINTEGA and glembatumumab vedotin commercial planning costs over the $2.6 million spent in the comparable period in 2014.

Net loss: Net loss was $32.0 million, or ($0.32) per share, for the third quarter of 2015 and $94.5 million, or ($0.98) per share, for the nine months ended September 30, 2015, compared to a net loss of $28.1 million, or ($0.31) per share and $86.3 million, or ($0.97) per share for the comparable periods in 2014.

Financial guidance: Celldex expects that its cash, cash equivalents and marketable securities will be sufficient to fund our operating expenses and capital expenditure requirements through 2017; however, this could be impacted by our clinical data results from the RINTEGA program and their potential impact on our pace of commercial manufacturing and the rate of expansion of our commercial operations.

On November 5, 2015 Bio-Path Holdings, Inc., (NASDAQ: BPTH) ("Bio-Path"), a biotechnology company developing a liposomal delivery technology for nucleic acid cancer drugs, reported that Dr. Jorge Cortes, Deputy Chair of the Department of Leukemia at the University of Texas MD Anderson Cancer Center and Chair of Bio-Path’s Scientific Advisory Board, will present data from Bio-Path’s Phase I and Ib clinical trials of its lead product candidate BP-100-1.01 (Liposomal Grb-2 antisense) in the treatment of blood cancers during a poster session at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, Florida (Filing, 8-K, Bio-Path Holdings, NOV 5, 2015, View Source [SID:1234508025]).

Details for the poster presentation are as follows:

Title: "Safety, Pharmacokinetics, and Efficacy of BP-100-1.01 (Liposomal Grb-2 Antisense Oligonucleotide) in Patients with Refractory or Relapsed Acute Myeloid Leukemia (AML), Philadelphia Chromosome Positive Chronic Myelogenous Leukemia (CML), Acute Lymphoblastic Leukemia (ALL), and Myelodysplastic Syndrome (MDS)"

Session Name: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster III

Date: Monday, December 7, 2015

Presentation Time: 6:00 p.m. – 8:00 p.m. Eastern Time

Location: Hall A, Orange County Convention Center

The poster will highlight results from Bio-Path’s Phase I and Ib clinical trials in patients with blood cancers, notably the complete remission (CR) of one patient with advanced acute myeloid leukemia (AML) who was treated with BP-100-1.01 in combination with low-dose cytarabine (LDAC) chemotherapy and another patient with chronic myelogenous leukemia (CML) who showed significant reduction (81 percent to 5 percent) in bone marrow blasts. The results suggest possible disease inhibition with BP-100-1.01 treatment.

The full abstract can be found at View Source

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On November 5, 2015 ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) reported the schedule of several data presentations on Iclusig (ponatinib) that will take place at the 57th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) being held in Orlando, December 5 to 8, 2015 (Press release, Ariad, NOV 5, 2015, View Source;p=RssLanding&cat=news&id=2107604 [SID:1234508024]). A total of six abstracts were accepted at ASH (Free ASH Whitepaper). The schedule and meeting location for key sessions at ASH (Free ASH Whitepaper), together with the abstract information, are listed below:

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Oral Presentation:

Title: The Impact of Ponatinib vs. Allogeneic Stem Cell Transplant (SCT) on Outcomes in Patients with Chronic Myeloid Leukemia (CML) or Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph + ALL) with the T315I Mutation
Oral Session: Chronic Myeloid Leukemia – Therapy and Prognosis
Date & Time: Monday, December 7, 2015, 7:00 – 8:30 a.m., Presentation at 8:15 a.m.
Abstract No.: 480
Presenter: Franck E. Nicolini, M.D., PhD (Centre Hospitalier Lyon Sud, Pierre-Bénite, France)
Location: Orange County Convention Center, Orange County Convention Center, Valencia BC (W415BC)

Clinical Poster Presentations:

Title: Real-World Ponatinib Prescribing Patterns and Outcomes in US Patients
Poster Session: Chronic Myeloid Leukemia – Therapy: Poster I
Date & Time: Saturday, December 5, 2015, 5:30 – 7:30 p.m.
Abstract No.: 1591
Presenter: Michael J. Mauro, M.D. (Memorial Sloan Kettering Cancer Center)
Location: Orange County Convention Center, Hall A

Title: Relationship of Line of Therapy to Efficacy for Ponatinib in 3rd-Line vs. 4th-Line Chronic-Phase Chronic Myeloid Leukemia (CML)
Poster Session: Chronic Myeloid Leukemia –Therapy: Poster I
Date & Time: Saturday, December 5, 2015, 5:30 – 7:30 p.m.
Abstract No.: 1588
Presenter: Moshe Yair Levy, M.D. (Baylor University Med Center, Dallas, TX)
Location: Orange County Convention Center, Hall A

Title: A Multi-Institutional Retrospective Analysis of Tyrosine Kinase Inhibitor (TKI) Clinical and Preclinical Efficacy According to BCR-ABL Mutation Status in CP-CML Patients
Poster Session: Chronic Myeloid Leukemia – Therapy: Poster II
Date & Time: Sunday, December 6, 2015 at 6:00 – 8:00 p.m.
Abstract No.: 2790
Presenter: Victor M. Rivera, Ph.D. (ARIAD Pharmaceuticals, Inc.)
Location: Orange County Convention Center, Hall A

Title: Efficacy and Safety of Ponatinib in CP-CML Patients by Number of Prior Tyrosine Kinase Inhibitors: 4-Year Follow-up of the Phase 2 PACE Trial
Poster Session: Chronic Myeloid Leukemia – Therapy: Poster III
Date & Time: Monday, December 7, 2015, 6:00 – 8:00 p.m.
Abstract No.: 4025
Author: Andreas Hochhaus, M.D. (Jena University Hospital, Jena, Germany)
Location: Orange County Convention Center, Hall A

Preclinical Poster Presentation:

Title: Potent Preclinical Activity of Ponatinib in Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma (GCB-DLBCL) Models
Poster Session: Lymphoma: Pre-Clinical- Chemotherapy and Biologic Agents: Poster III
Date & Time: Monday, December 7, 2015, 6:00 – 8:00 p.m.
Abstract No.: 4000
Presenter: Joe Gozgit, Ph.D. (ARIAD Pharmaceuticals, Inc.)
Location: Orange County Convention Center, Hall A

About Iclusig (ponatinib) tablets

Iclusig is approved in the U.S., EU, Australia, Switzerland, Israel and Canada.

In the U.S., Iclusig is a kinase inhibitor indicated for the:

Treatment of adult patients with T315I-positive chronic myeloid leukemia (chronic phase, accelerated phase, or blast phase) or T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).

Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated.

These indications are based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with Iclusig.

IMPORTANT SAFETY INFORMATION, INCLUDING THE BOXED WARNING

WARNING: VASCULAR OCCLUSION, HEART FAILURE, and HEPATOTOXICITY

See full prescribing information for complete boxed warning

Vascular Occlusion: Arterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig treated patients, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients less than 50 years old, experienced these events. Monitor for evidence of thromboembolism and vascular occlusion. Interrupt or stop Iclusig immediately for vascular occlusion. A benefit risk consideration should guide a decision to restart Iclusig therapy.
Heart Failure, including fatalities, occurred in 8% of Iclusig-treated patients. Monitor cardiac function. Interrupt or stop Iclusig for new or worsening heart failure.

Hepatotoxicity, liver failure and death have occurred in Iclusig-treated patients. Monitor hepatic function. Interrupt Iclusig if hepatotoxicity is suspected.

Vascular Occlusion: Arterial and venous thrombosis and occlusions, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures have occurred in at least 27% of Iclusig-treated patients from the phase 1 and phase 2 trials. Iclusig can also cause recurrent or multi-site vascular occlusion. Overall, 20% of Iclusig-treated patients experienced an arterial occlusion and thrombosis event of any grade. Fatal and life-threatening vascular occlusion has occurred within 2 weeks of starting Iclusig treatment and in patients treated with average daily dose intensities as low as 15 mg per day. The median time to onset of the first vascular occlusion event was 5 months. Patients with and without cardiovascular risk factors have experienced vascular occlusion although these events were more frequent with increasing age and in patients with prior history of ischemia, hypertension, diabetes, or hyperlipidemia. Interrupt or stop Iclusig immediately in patients who develop vascular occlusion events.

Heart Failure: Fatal and serious heart failure or left ventricular dysfunction occurred in 5% of Iclusig-treated patients (22/449). Eight percent of patients (35/449) experienced any grade of heart failure or left ventricular dysfunction. Monitor patients for signs or symptoms consistent with heart failure and treat as clinically indicated, including interruption of Iclusig. Consider discontinuation of Iclusig in patients who develop serious heart failure.

Hepatotoxicity: Iclusig can cause hepatotoxicity, including liver failure and death. Fulminant hepatic failure leading to death occurred in an Iclusig-treated patient within one week of starting Iclusig. Two additional fatal cases of acute liver failure also occurred. The fatal cases occurred in patients with blast phase CML (BP-CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Severe hepatotoxicity occurred in all disease cohorts. Iclusig treatment may result in elevation in ALT, AST, or both. Monitor liver function tests at baseline, then at least monthly or as clinically indicated. Interrupt, reduce or discontinue Iclusig as clinically indicated.

Hypertension: Treatment-emergent hypertension (defined as systolic BP≥140 mm Hg or diastolic BP≥90 mm Hg on at least one occasion) occurred in 67% of patients (300/449). Eight patients treated with Iclusig (2%) experienced treatment-emergent symptomatic hypertension as a serious adverse reaction, including one patient (<1%) with hypertensive crisis. Patients may require urgent clinical intervention for hypertension associated with confusion, headache, chest pain, or shortness of breath. In 131 patients with Stage 1 hypertension at baseline, 61% (80/131) developed Stage 2 hypertension. Monitor and manage blood pressure elevations during Iclusig use and treat hypertension to normalize blood pressure. Interrupt, dose reduce, or stop Iclusig if hypertension is not medically controlled.

Pancreatitis: Clinical pancreatitis occurred in 6% (28/449) of patients (5% Grade 3) treated with Iclusig. Pancreatitis resulted in discontinuation or treatment interruption in 6% of patients (25/449). The incidence of treatment-emergent lipase elevation was 41%. Check serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated. Consider additional serum lipase monitoring in patients with a history of pancreatitis or alcohol abuse. Dose interruption or reduction may be required. In cases where lipase elevations are accompanied by abdominal symptoms, interrupt treatment with Iclusig and evaluate patients for pancreatitis. Do not consider restarting Iclusig until patients have complete resolution of symptoms and lipase levels are less than 1.5 x ULN.

Neuropathy: Peripheral and cranial neuropathy have occurred in Iclusig-treated patients. Overall, 13% (59/449) of Iclusig-treated patients experienced a peripheral neuropathy event of any grade (2%, grade 3/4). In clinical trials, the most common peripheral neuropathies reported were peripheral neuropathy (4%, 18/449), paresthesia (4%, 17/449), hypoesthesia (2%, 11/449), and hyperesthesia (1%, 5/449). Cranial neuropathy developed in 1% (6/449) of Iclusig-treated patients (<1% grade 3/4). Of the patients who developed neuropathy, 31% (20/65) developed neuropathy during the first month of treatment. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness. Consider interrupting Iclusig and evaluate if neuropathy is suspected.

Ocular Toxicity: Serious ocular toxicities leading to blindness or blurred vision have occurred in Iclusig-treated patients. Retinal toxicities including macular edema, retinal vein occlusion, and retinal hemorrhage occurred in 3% of Iclusig-treated patients. Conjunctival or corneal irritation, dry eye, or eye pain occurred in 13% of patients. Visual blurring occurred in 6% of the patients. Other ocular toxicities include cataracts, glaucoma, iritis, iridocyclitis, and ulcerative keratitis. Conduct comprehensive eye exams at baseline and periodically during treatment.

Hemorrhage: Serious bleeding events, including fatalities, occurred in 5% (22/449) of patients treated with Iclusig. Hemorrhagic events occurred in 24% of patients. The incidence of serious bleeding events was higher in patients with accelerated phase CML (AP-CML), BP-CML, and Ph+ ALL. Most hemorrhagic events, but not all occurred in patients with grade 4 thrombocytopenia. Interrupt Iclusig for serious or severe hemorrhage and evaluate.

Fluid Retention: Serious fluid retention events occurred in 3% (13/449) of patients treated with Iclusig. One instance of brain edema was fatal. In total, fluid retention occurred in 23% of the patients. The most common fluid retention events were peripheral edema (16%), pleural effusion (7%), and pericardial effusion (3%). Monitor patients for fluid retention and manage patients as clinically indicated. Interrupt, reduce, or discontinue Iclusig as clinically indicated.

Cardiac Arrhythmias: Symptomatic bradyarrhythmias that led to a requirement for pacemaker implantation occurred in 1% (3/449) of Iclusig-treated patients. Advise patients to report signs and symptoms suggestive of slow heart rate (fainting, dizziness, or chest pain). Supraventricular tachyarrhythmias occurred in 5% (25/449) of Iclusig-treated patients. Atrial fibrillation was the most common supraventricular tachyarrhythmia and occurred in 20 patients. For 13 patients, the event led to hospitalization. Advise patients to report signs and symptoms of rapid heart rate (palpitations, dizziness). Interrupt Iclusig and evaluate.

Myelosuppression: Severe (grade 3 or 4) myelosuppression occurred in 48% (215/449) of patients treated with Iclusig. The incidence of these events was greater in patients with AP-CML, BP-CML and Ph+ ALL than in patients with CP-CML. Obtain complete blood counts every 2 weeks for the first 3 months and then monthly or as clinically indicated, and adjust the dose as recommended.

Tumor Lysis Syndrome: Two patients (<1%) with advanced disease (AP-CML, BP-CML, or Ph+ ALL) treated with Iclusig developed serious tumor lysis syndrome. Hyperuricemia occurred in 7% (30/449) of patients overall; the majority had CP-CML (19 patients). Due to the potential for tumor lysis syndrome in patients with advanced disease, ensure adequate hydration and treat high uric acid levels prior to initiating therapy with Iclusig.

Compromised Wound Healing and Gastrointestinal Perforation: Since Iclusig may compromise wound healing, interrupt Iclusig for at least 1 week prior to major surgery. Serious gastrointestinal perforation (fistula) occurred in one patient 38 days post-cholecystectomy.

Embryo-Fetal Toxicity: Iclusig can cause fetal harm. If Iclusig is used during pregnancy, or if the patient becomes pregnant while taking Iclusig, the patient should be apprised of the potential hazard to the fetus. Advise women to avoid pregnancy while taking Iclusig.

Most common non-hematologic adverse reactions: (≥20%) were hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, and pyrexia. Hematologic adverse reactions included thrombocytopenia, anemia, neutropenia, lymphopenia, and leukopenia.

On November 5, 2015 Medigene AG (MDG1, Frankfurt, Prime Standard) reported that early clinical data of its dendritic cell (DC) vaccines will be presented at the upcoming ASH (Free ASH Whitepaper) Annual Meeting taking place from December 5 – 8, 2015 in Orlando, Florida, USA, by its partner Oslo University Hospital, Norway (Press release, MediGene, NOV 5, 2015, View Source [SID:1234508023]). The clinical data were collected in an ongoing compassionate use[1] programme conducted by the Oslo University Hospital under the responsibility of Prof. Gunnar Kvalheim. The poster presentation shows data from patients with acute myeloid leukaemia (AML) and is entitled "AML Patients in Minimal Residual Disease Vaccinated with a Novel Generation of Fast Dendritic Cells Expressing WT-1 and PRAME Mount Specific Immune Responses That Relate to Clinical Outcome". The poster will be presented on December 7, 2015 at 6 PM – 8 PM (local time).

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The Oslo University Hospital has an agreement with Medigene for the use of Medigene`s new generation DC vaccines for their ongoing academic clinical studies. Medigene’s DC vaccines are produced according to GMP guidelines at the Department of Cellular Therapy at the Oslo University Hospital. Acute myeloid leukaemia is Medigene’s lead indication in its DC vaccine programme.

Link to the Abstract: View Source

About Medigene’s DC vaccines: The platform for the development of antigen-tailored DC vaccines is the most advanced platform of the three highly innovative and complementary immunotherapy platforms of Medigene Immunotherapies. Currently, Medigene evaluates its DC vaccines in a company-sponsored phase I/II clinical trial in acute myeloid leukaemia (AML). Further studies utilizing Medigene’s DC vaccine technology include two ongoing clinical investigator-initiated trials: a clinical phase I/II trial in AML at the Ludwig-Maximilian University Hospital Großhadern, Munich, and a clinical phase II trial in prostate cancer at Oslo University Hospital. Moreover, a compassionate use programme is being conducted at the Department of Cellular Therapy at Oslo University Hospital.

Dendritic cells (DCs) are the most potent antigen presenting cells of our immune system. Their task is to take up, process and present antigens on their cell surface, which enables them to activate antigen-specific T cells for maturation and proliferation. This way T cells can recognise and eliminate antigen-bearing tumour cells. Dendritic cells can also induce natural killer cells (NK cells) to attack tumour cells. The team of Medigene Immunotherapies GmbH’s scientists has developed new, fast and efficient methods for generating dendritic cells ex-vivo, which have relevant characteristics to activate both T cells and NK cells. The DC vaccines are developed from autologous (patient-specific) precursor cells, isolated from the patient’s blood, and can be loaded with tumor-specific antigens to treat different types of cancer. Medigene’s DC vaccines are in development for the treatment of minimal residual disease or use in combination therapies.

On November 5, 2015 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that more than 45 abstracts featuring eight of its approved or investigational medicines will be presented during the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting from December 5-8 in Orlando (Press release, Genentech, NOV 5, 2015, View Source [SID:1234508022]). The abstracts include more than 15 oral presentations across a broad range of molecular targets and combinations, as well as different clinical endpoints that Genentech is exploring in various blood diseases and lines of treatment.

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"Our data at ASH (Free ASH Whitepaper) this year showcase the evolution of our hematology portfolio and represent potential future approaches to helping people with blood cancers and blood disorders," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "We’re particularly excited about studies evaluating new combinations with Gazyva and venetoclax, as well as studies examining the potential clinical significance of minimal residual disease negativity."

Data for Gazyva include results from combination studies such as the Phase IIIb GREEN study and the pivotal CLL11 and GADOLIN studies. GREEN results will include data for Gazyva in combination with bendamustine in previously untreated chronic lymphocytic leukemia (CLL). Genentech will also share updated results from the Phase III CLL11 study, which formed the basis of the Gazyva approval in previously untreated CLL in combination with chlorambucil, and further data from the pivotal Phase III GADOLIN study for the investigational use of Gazyva in patients with indolent non-Hodgkin’s lymphoma (NHL) that is refractory to Rituxan (rituximab)-based treatment, that add to the positive results presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June this year.

Genentech will also present findings from multiple studies that suggest a potential role for minimal residual disease (MRD)-negativity in the treatment of certain blood cancers. In collaboration with AbbVie, Genentech will share new data for investigational medicine venetoclax as a monotherapy or in combinations across a number of blood cancers, including CLL, NHL, multiple myeloma (MM) and acute myeloid leukemia (AML). Data will also be shown for investigational medicine ACE910, which was recently granted breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) for the prophylactic treatment of people who are 12 years or older with hemophilia A with factor VIII inhibitors.

The table below contains key abstracts featuring Genentech medicines that will be presented. Follow Genentech on Twitter via @Genentech and keep up to date with ASH (Free ASH Whitepaper) Annual Meeting news and updates by using the hashtag #ASH2015.

Separately, the FDA has accepted for priority review the company’s supplemental Biologics License Application (sBLA) for Gazyva in the treatment of patients with follicular lymphoma (FL) who relapsed after, or are refractory to a rituximab-containing regimen, based on GADOLIN study results. Marketing applications for Gazyva have also been submitted to other health authorities, including the European Medicines Agency, for approval consideration in the treatment of patients with FL who did not respond or who progressed during or up to six months after treatment with rituximab or a rituximab-containing regimen. In addition, AbbVie has submitted a New Drug Application (NDA) for venetoclax to the FDA under breakthrough therapy designation, based in part on results of the pivotal Phase II M13-982 study evaluating venetoclax in people with relapsed/refractory CLL harboring the 17p deletion. Genentech and AbbVie announced positive top-line results from this study earlier this year.

Gazyva Indication

Gazyva is a prescription medicine used with the chemotherapy drug, chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment.

Important Safety Information

Patients must tell their doctor right away about any side effects they experience. Gazyva can cause side effects that can become serious or life threatening, including:

Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If a patient has had history of hepatitis B infection, Gazyva could cause it to return. Patients should not receive Gazyva if they have active hepatitis B liver disease. The patient’s doctor or healthcare team will need to screen for hepatitis B before, and monitor the patient for hepatitis during and after, treatment with Gazyva. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes.

Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. A patient’s weakened immune system could put the patient at risk. The patient’s doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems.

Additional possible serious side effects of Gazyva:

Patients must tell their doctor right away about any side effects they experience. Gazyva can cause side effects that may become severe or life threatening, including:

Infusion Reactions: These side effects may occur during or within 24 hours of any Gazyva infusion. Some infusion reactions can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening infusion reactions. If a patient has a reaction, the infusion is either slowed or stopped until the patient’s symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the infusion reaction is serious, the infusion of Gazyva will be permanently stopped. The patient’s healthcare team will take steps to help lessen any side effects the patient may have to the infusion process. The patient may be given medicines to take before each Gazyva treatment. Signs of infusion reactions may include: dizziness, nausea, chills, fever, vomiting, diarrhea, breathing problems, and chest pain.

Tumor Lysis Syndrome (TLS): Gazyva works to break down cancer cells quickly. As cancer cells break apart, their contents are released into the blood. These contents may cause damage to organs and the heart, and may lead to kidney failure requiring the need for dialysis treatment. TLS, including death, has been reported in patients receiving Gazyva. The patient’s doctor may prescribe medication to help prevent TLS. The patient’s doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness.

Infections: While a patient is taking Gazyva, the patient may develop infections. Some of these infections may be severe. Fatal infections have been reported, so the patient should be sure to talk to the doctor if the patient thinks the patient has one. Patients with active infection should not be treated with Gazyva. Infections may continue even after the patient stops taking Gazyva. The patient’s doctor may prescribe medications to help prevent infections. Symptoms of infection include fever and cough.
Low White Blood Cell Count : When a patient has an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While the patient is taking Gazyva, the patient’s doctor will do blood work to check the patient’s white blood cell counts. Neutropenia can develop during or after treatment with Gazyva. It may also last for more than one month. If a patient’s white blood cell count is low, the patient’s doctor may prescribe medication to help prevent infections.

Low Platelet Count: Platelets help stop bleeding or blood loss. Gazyva may reduce the number of platelets the patient has in the blood. This may affect the clotting process. While the patient is taking Gazyva, the patient’s doctor will do blood work to check the patient’s platelet count.
Most common side effects of Gazyva

The most common side effects of Gazyva are infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.

Before receiving Gazyva, patients should talk to their doctor about:

Immunizations: Before receiving Gazyva therapy, the patient should tell the patient’s healthcare provider if the patient has recently received or is scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines.

Pregnancy: A patient should tell the doctor if the patient is pregnant, plans to become pregnant, or is breastfeeding. Gazyva may harm the unborn baby. Mothers who have been exposed to Gazyva during pregnancy should discuss the safety and timing of live virus vaccinations for their infants with their child’s healthcare providers. It is not known if Gazyva may pass into the patient’s breast milk. The patient should speak to the doctor about using Gazyva if the patient is breastfeeding.

Patients must tell their doctor about any side effects.

These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist.

Gazyva is available by prescription only.

Report side effects to the FDA at (800) FDA-1088, or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the full Prescribing Information, including Boxed WARNINGS, for additional Important Safety Information.

Rituxan Indications

Rituxan (rituximab) is indicated for the treatment of patients with:

Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
Previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy and, in patients achieving a complete or partial response to Rituxan in combination with chemotherapy, as single-agent maintenance therapy
Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy
Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens
Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC)
Rituxan is not recommended for use in patients with severe, active infections.

Important Safety Information:

Rituxan can cause serious side effects that can lead to death, including:

Infusion Reactions: may occur during or within 24 hours of the infusion. The patient’s doctor should give the patient medicines before their treatment. Symptoms can include hives, rash, itching, facial or oral swelling, sudden cough, shortness of breath, difficulty breathing, weakness, dizziness, feeling faint, racing heart or chest pain.
Severe Skin and Mouth Reactions: symptoms can include painful sores, ulcers, or blisters on the skin, lips or mouth; peeling skin; rash; or pustules.

Hepatitis B Virus (HBV) Reactivation: may cause serious liver problems including liver failure and death. If patients have had hepatitis B or are carriers of HBV, receiving Rituxan could cause the virus to become an active infection again. Patient should not receive Rituxan if they have active HBV liver disease. The patient’s doctor will do blood tests to check for HBV infection prior to treatment and will monitor the patient during and for several months following their treatment.
Progressive Multifocal Leukoencephalopathy (PML): a rare, serious brain infection that can lead to severe disability and death and for which there is no known prevention, treatment or cure. Symptoms can include difficulty thinking, loss of balance, changes in speech or walking, weakness on one side of the body or blurred or lost vision.
What are the additional possible serious side effects of Rituxan?

Patients must tell their doctor right away about any side effects they experience. Rituxan can cause serious side effects that can lead to death, including:

Tumor Lysis Syndrome (TLS): may cause kidney failure and the need for dialysis treatment, abnormal heart rhythm and can lead to death. The patient’s doctor may give the patient medicines before their treatment to help prevent TLS.
Serious Infections: can happen during and after treatment and can lead to death. These infections may be bacterial, fungal or viral. Symptoms can include fever; cold or flu symptoms; earache or headache; pain during urination; white patches in the mouth or throat; cuts or scrapes that are red, warm, swollen or painful.
Heart Problems: symptoms can include chest pain and irregular heartbeats that may require treatment. The patient’s doctor may need to stop their treatment.
Kidney Problems: the patient’s doctor should do blood tests to check how well the patient’s kidneys are working.
Stomach and Serious Bowel Problems: can include blockage or tears in the bowel that can lead to death. Stomach area pain during treatment can be a symptom.
Low Blood Cell Counts: the patient’s blood cell counts may be monitored during treatment.
The most common side effects of Rituxan are infusion reactions, chills, infections, body aches, tiredness and low white blood cells.

Patients must tell their doctor if they are pregnant, plan to become pregnant or are breastfeeding. It is not known if Rituxan may harm the patient’s unborn baby or pass into the patient’s breast milk. Women should use birth control while using Rituxan and for 12 months after treatment.

Patients must tell their doctor about any side effect that bothers them or that does not go away.

These are not all of the possible side effects of Rituxan. For more information, patients should ask their doctor or pharmacist.

Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please see the Rituxan full Prescribing Information, including Most Serious Side Effects, for additional important safety information at View Source