On December 5, 2015 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported updated data from the pivotal CLL11 study confirming that Gazyva (obinutuzumab) plus chlorambucil reduced the risk of disease worsening or death by more than half compared to Rituxan (rituximab) plus chlorambucil (progression-free survival, PFS; HR=0.46, median PFS 28.7 months versus 15.7 months; p<0.0001) (Press release, Genentech, DEC 5, 2015, View Source [SID:1234508546]). New results to be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting from a secondary endpoint that measured time to next treatment (TTNT) showed that, after completing the set six-month Gazyva regimen, people remained treatment-free for nearly four years on average before needing the next treatment for their cancer (TTNT; 51.1 months, including the six-month initial treatment period). No unexpected safety signals were observed with Gazyva.

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"These updated CLL11 data confirmed that Gazyva helped people with previously untreated chronic lymphocytic leukemia live significantly longer without disease worsening or death compared to Rituxan," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "After a fixed course of therapy with Gazyva, people remained treatment-free for nearly four years on average. Time free from treatment is an important consideration for a disease like CLL, which occurs in older adults who frequently have other health issues. "

In the GREEN safety study, data from a subgroup analysis showed there were no unexpected safety signals when Gazyva was combined with bendamustine. In addition, nearly 80 percent of people responded to treatment with Gazyva plus bendamustine (overall response rate, ORR), and a third of people (32.3 percent) achieved a complete response (CR). A substantial number of people were also minimal residual disease (MRD)-negative when measured in the bone marrow or blood (28 percent and 59 percent, respectively), which means no cancer can be detected using a specific test. ORR and MRD-negativity were secondary endpoints of the study.

Gazyva in combination with chlorambucil is approved in the United States for use in people with previously untreated CLL and in the EU for use in people with previously untreated CLL who have co-existing medical conditions (comorbidities) making them unsuitable for an intensive therapy (full-dose fludarabine based therapy).

About the CLL11 Study

CLL11 is a Phase III, multicenter, open-label, randomized three-arm study investigating the efficacy and safety profile of Gazyva plus chlorambucil, Rituxan plus chlorambucil and chlorambucil alone in 781 people with previously untreated CLL. Stage 1 (n=589) compared Gazyva plus chlorambucil to chlorambucil alone and Rituxan plus chlorambucil to chlorambucil alone. Stage 2 (n=663) compared Gazyva plus chlorambucil with Rituxan plus chlorambucil.

The primary endpoint of the study was PFS and secondary endpoints included ORR, overall survival (OS), CR, response duration, disease free survival (DFS), TTNT, MRD-negativity and safety profile.

The updated analysis from CLL11 will be presented at a poster session on Saturday, December 5 at 5:30 P.M. EST (Abstract #1733).

About the GREEN Study

GREEN is an ongoing Phase IIIb safety study. This multicenter, open-label, single-arm study is evaluating the safety and efficacy of Gazyva alone or in combination with chemotherapy, including bendamustine, in people with previously untreated or relapsed/refractory CLL. The primary endpoint of the study was safety with secondary endpoints including ORR and MRD-negativity.

The study included a subgroup of people who were previously untreated and who received treatment with Gazyva in combination with bendamustine. Data from this subgroup analysis will be presented at an oral presentation on Monday, December 7 at 7:00 A.M. EST (Abstract #493).

About Chronic Lymphocytic Leukemia (CLL)

CLL is one of the most common forms of blood cancer and in 2015, it is expected that there will be about 4,650 deaths from CLL in the United States. Most cases of CLL (95 percent) start in white blood cells called B-cells that have a protein called CD20 on their surface.

About Gazyva

Gazyva is an engineered monoclonal antibody designed to attach to CD20, a protein found only on B-cells. It attacks targeted cells both directly and together with the body’s immune system. Gazyva is thought to have an increased ability to induce direct cell death and induces greater activity in how it recruits the body’s immune system to attack B-cells (antibody dependent cellular cytotoxicity; ADCC) when compared to Rituxan. Gazyva was discovered by Roche Glycart AG, a wholly owned, independent research unit of Roche. In the United States, Gazyva is part of a collaboration between Genentech and Biogen Idec.

Gazyva is being studied in a large clinical program, including the Phase III GOYA and GALLIUM studies. GOYA is comparing Gazyva head-to-head with Rituxan plus chemotherapy in first line diffuse large B-cell lymphoma (DLBCL) and GALLIUM is comparing Gazyva plus chemotherapy head-to-head with Rituxan plus chemotherapy in first line indolent non-Hodgkin’s lymphoma (NHL). Additional combination studies investigating Gazyva with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are planned or underway across a range of blood cancers.

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.

On December 5, 2015 Novartis reported that five-year treatment with Jakavi (ruxolitinib) suggested an overall survival advantage for patients with myelofibrosis (MF), despite crossover to Jakavi from the best available therapy arm after the primary analysis at 48 weeks (intent-to-treat analysis: 33% reduction in risk of death, hazard ratio=0.67 [95% confidence interval (CI), 0.44-1.02], crossover-corrected hazard ratio=0.44 [95% CI, 0.18-1.04]) (Press release, Novartis, DEC 5, 2015, View Source [SID:1234508421]). In the COMFORT-II (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy) Phase III study, more than half of the patients with MF (53.4%) also experienced significant reductions (>=35%) in spleen size with Jakavi therapy, and sustained this benefit over prolonged periods of time (median duration of 3.2 years)[1]. Findings from this study were presented at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting (ASH) (Free ASH Whitepaper) in Orlando, Florida.

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"Given that patients with myelofibrosis have shortened survival expectations and are at an increased risk of complications, the five-year findings from COMFORT-II demonstrate a long-term benefit with Jakavi therapy that is meaningful to the community," said Claire Harrison, MD, study investigator and Consultant Hematologist, Guy’s and St. Thomas’ NHS Foundation Trust, London. "These data help to confirm the important role Jakavi plays in these difficult-to-treat patients."

In addition to the Jakavi data presented at ASH (Free ASH Whitepaper), Novartis announced that a separate Phase III study met its primary endpoint-patients with polycythemia vera (PV) resistant to or intolerant of hydroxyurea who did not have an enlarged spleen who were treated with Jakavi maintained hematocrit control without the need for phlebotomy. In the Phase III RESPONSE 2 (Randomized Study of Efficacy and Safety in POlycythemia Vera with JAK INhibitor Ruxolitinib VerSus BEst Available Care) study, the safety profile of Jakavi was consistent with previous studies. Full results from the trial continue to be evaluated and will be presented at a future medical congress.

"The growing body of research confirms the benefit of Jakavi for patients with rare blood cancers, such as myelofibrosis and polycythemia vera, who have limited treatment options," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. "In addition to exhibiting long-term benefits in myelofibrosis, Jakavi also showed potential to benefit a broader population of patients with polycythemia vera, bringing hope to another underserved patient community."

About the COMFORT-II Study
COMFORT-II (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy) is a randomized, open-label, Phase III study of 219 patients with primary MF, post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF) in 56 study locations in Europe. Two-thirds of patients (146) received Jakavi twice daily and one-third of patients (73) received best available therapy, which was administered at doses and schedules determined by the investigator. Best available therapy was selected by the investigator for each patient and could have included a combination of available agents to treat the disease and/or its symptoms. Of the patients on the best available therapy arm, 61.6% crossed over to receive Jakavi upon protocol-defined progression following the primary analysis after week 48. All patients randomized to best available therapy have crossed over or discontinued. An analysis of the study at five years was performed to evaluate the safety and efficacy of Jakavi in patients with MF[1].

In the Phase III trial, fibrosis grades, a key indicator of disease control in MF, improved (15.8%) or were maintained (32.2%) in nearly half of patients with long-term Jakavi treatment. Nearly one-quarter of patients (26.7% from Jakavi treatment arm; 24.4% who crossed over from best available treatment arm) remained on treatment with Jakavi for five years. All adverse events (AEs) were consistent with previous analyses of treatment with Jakavi in patients with MF. The most common AEs in Jakavi-treated patients either after randomization or after crossing over from best available therapy were thrombocytopenia (52.4%), anemia (49.2%), diarrhea (35.6%) and peripheral edema (33.0%). The most common grade 3/4 AEs included anemia (22.5%), thrombocytopenia (15.2%), pneumonia (5.8%), general physical health deterioration (4.2%) and shortness of breath (4.2%)[1].

About the RESPONSE 2 Study
RESPONSE 2 (Randomized Study of Efficacy and Safety in POlycythemia Vera with JAK INhibitor Ruxolitinib VerSus BEst Available Care) is a multi-center, open label, randomized, Phase IIIb study evaluating the efficacy and safety of Jakavi versus best available therapy. The trial randomized 149 patients with PV who were resistant to or intolerant of hydroxyurea, dependent on phlebotomy for hematocrit control and did not have an enlarged spleen. Patients were randomized 1:1, by stratification (based on hydroxyurea resistance or intolerance) to receive either Jakavi (10 mg twice daily) or best available therapy, which was defined as investigator selected monotherapy or observation only. The dose was adjusted as needed throughout the study.

About Myelofibrosis
MF is part of a group of related rare blood cancers known as myeloproliferative neoplasms (MPNs) where a patient’s bone marrow can no longer produce enough normal blood cells, causing the spleen to enlarge[2]. As a result, patients with MF may suffer from debilitating symptoms and have a poor quality of life[4]. After diagnosis, patients with MF have a decreased life expectancy, with an average survival of approximately five to six years[5]. Although allogeneic stem cell transplantation may cure MF, the procedure is associated with significant morbidity and transplant-related mortality, and is available to less than 5% of patients who are young and fit enough to undergo the procedure[6].

About Polycythemia Vera
Also an MPN, PV is associated with an overproduction of blood cells in the bone marrow and affects roughly one to three people per 100,000 globally[3],[7]. The disease is driven by the dysregulation of the JAK-STAT pathway[8]. It is typically characterized by elevated hematocrit, the volume percentage of red blood cells in whole blood, which can lead to a thickening of the blood and an increased risk of blood clots, as well as an elevated white blood cell and platelet count[3]. This can cause serious cardiovascular complications, such as stroke and heart attack, resulting in increased morbidity and mortality[9]. Approximately 60 to 70% of patients with PV do not have enlarged spleen[10].

A common PV treatment includes phlebotomy, a procedure to remove blood from the body to reduce the concentration of red blood cells, which is used to help maintain a hematocrit level below 45%[3],[9]. However, for a subset of patients, including those with high-risk PV, phlebotomy is usually unsuitable as a permanent treatment option due to its inability to control symptoms or effectively manage the overproduction of red blood cells, therefore cytoreductive agents, such as hydroxyurea, may be added[9]. For patients requiring phlebotomy in combination with hydroxyurea, hematocrit may fluctuate and remain at unsafe levels for significant periods of time[11]. Unfortunately, approximately 25% of patients with PV become resistant to or intolerant of hydroxyurea treatment according to European LeukemiaNet (ELN) criteria, resulting in inadequate disease control and an increased risk of progression[12].

About Jakavi
Jakavi (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. Jakavi is approved by the European Commission for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea and for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (MF) (also known as chronic idiopathic MF), post-polycythemia vera MF or post-essential thrombocythemia MF. Jakavi is approved in more than 95 countries for patients with MF, including countries in the European Union, Canada, Japan and countries in Asia, Latin and South America, and in 49 countries for patients with PV, including countries in the European Union, Japan and Canada. The exact indication for Jakavi varies by country. Additional worldwide regulatory filings are underway in MF and PV.

Novartis licensed ruxolitinib from Incyte Corporation for development and commercialization outside the United States. Jakavi is marketed in the United States by Incyte Corporation as Jakafi for the treatment of patients with PV who have had an inadequate response to or are intolerant of hydroxyurea and for the treatment of patients with intermediate or high-risk MF.

The recommended starting dose of Jakavi in PV is 10 mg given orally twice daily. The recommended starting dose of Jakavi in MF is 15 mg twice daily for patients with a platelet count between 100,000 cubic millimeters (mm3) and 200,000 mm3, and 20 mg twice daily for patients with a platelet count of >200,000 mm3. Doses may be titrated based on safety and efficacy. There is limited information to recommend a starting dose for MF and PV patients with platelet counts between 50,000/mm3 and <100,000/mm3. The maximum recommended starting dose in these patients is 5 mg twice daily, and patients should be titrated cautiously[13].

Jakavi is a registered trademark of Novartis AG in countries outside the United States. Jakafi is a registered trademark of Incyte Corporation. The safety and efficacy profile of Jakavi has not yet been established outside the approved indications.

Jakavi Important Safety Information for Treatment of Myelofibrosis (MF) and Polycythemia Vera (PV)
Jakavi can cause serious side effects, including a decrease in blood cell count and infections. Complete blood count monitoring is recommended. Dose reduction or interruption may be required in patients with any hepatic impairment or severe renal impairment or in patients developing hematologic adverse reactions such as thrombocytopenia, anemia and neutropenia. Dose reductions are also recommended when Jakavi is co-administered with strong CYP3A4 inhibitors or fluconazole. Use of Jakavi during pregnancy is not recommended, and women should avoid becoming pregnant during Jakavi therapy. Women taking Jakavi should not breast feed. Progressive multifocal leukoencephalopathy (PML) has been reported. Physicians should be alert for neuropsychiatric symptoms suggestive of PML. Hepatitis B viral load (HBV-DNA titer) increases have been reported in patients with chronic HBV infections. Patients with chronic HBV infection should be treated and monitored according to clinical guidelines. Non-melanoma skin cancer (NMSC) has been reported in Jakavi treated patients. Periodic skin examination is recommended. Very common adverse reactions in MF (>10%) include urinary tract infections, anemia, thrombocytopenia, neutropenia, hypercholesterolemia, dizziness, headache, alanine aminotransferase increased, aspartate aminotransferase increased, bruising and weight gain. Common adverse reactions in MF (1 to 10%) include herpes zoster and flatulence. Uncommon adverse reactions in MF include tuberculosis. Very common adverse reactions in PV (>10%) include anemia, thrombocytopenia, hypercholesterolemia, hypertriglyceridemia, dizziness, alanine aminotransferase increased and aspartate aminotransferase increased. Common adverse reactions in PV (1 to 10%) include urinary tract infections, herpes zoster, weight gain, constipation and hypertension.

On December 5, 2015 Incyte Corporation (Nasdaq:INCY) reported data from two Phase 3 studies evaluating the long-term safety and efficacy of Jakafi (ruxolitinib) in patients with Myeloproliferative Neoplasms (MPNs) (Press release, Incyte, DEC 5, 2015, View Source;p=RssLanding&cat=news&id=2120390 [SID:1234508420]). In myelofibrosis (MF), results of a five-year follow-up from the COMFORT-II study demonstrate a continued survival benefit in patients originally randomized to ruxolitinib compared with patients randomized to best available therapy (BAT), with a 33 percent reduction in the risk of death (HR, 0.67; 95%CI, 0.44-1.02; P=.06). Because patients in the BAT arm had crossed over to receive ruxolitinib therapy (median 17 months after randomization), these data may suggest that earlier treatment with ruxolitinib may be associated with improved long-term survival in patients with intermediate-2 or high-risk MF. Additionally, 53 percent of patients treated with ruxolitinib (n=78/146) achieved at least a 35 percent reduction in spleen volume from baseline that was sustained over time (median duration 3.2 years).

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"These data from the COMFORT-II study reinforce the positive and long-term clinical benefits seen in patients with myelofibrosis who are treated with Jakafi," said Rich Levy, MD, Chief Drug Development Officer, Incyte. "The reduction in the risk of death and the sustained improvements in spleen volume are meaningful and important results for the community of patients with this rare blood cancer."

An analysis of the RESPONSE study is also planned for presentation at ASH (Free ASH Whitepaper). Previously published results in the New England Journal of Medicine showed that treatment with ruxolitinib, compared to standard therapy improved hematocrit control and reduced spleen volume in patients with polycythemia vera (PV) who had an inadequate response to or had unacceptable side effects from hydroxyurea (HU). The data at ASH (Free ASH Whitepaper) demonstrate that in patients with elevated white blood cell (WBC) counts at baseline, a greater proportion of patients in the ruxolitinib treatment arm (45%) achieved normalization of their WBC counts (achieving a WBC ≤10×109/L or a ≥50% reduction from baseline) compared to BAT (22%) or HU (9%) at week 32.
These data are scheduled for presentation at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place December 5-8, 2015 in Orlando, FL.

Results from the COMFORT-II Study

Data from a five-year follow-up of the COMFORT-II trial, a randomized, open-label Phase 3 study evaluating long-term safety and efficacy of ruxolitinib in patients with intermediate-2 or high-risk primary myelofibrosis, post-PV myelofibrosis, or post-ET myelofibrosis, allowing crossover from the BAT arm to ruxolitinib after 48 weeks upon protocol-defined progression, revealed that 53 percent of patients treated with ruxolitinib (n=78/146) achieved at least a 35 percent reduction in spleen volume from baseline while on treatment during the study. Additionally, approximately one-third of evaluable JAK2 V617F-positive patients had more than a 20 percent reduction in allele burden at 3.2 years (38%) and 3.7 years (31%). Patients treated with ruxolitinib also experienced improvements in bone marrow fibrosis (15.8%) with 32.2 percent reporting stable fibrosis scores.

Overall, 59 (40%) and 35 (48%) deaths were reported in the ruxolitinib and BAT arms, respectively. Median overall survival (OS) was not reached in the ruxolitinib arm and was 4.1 years in the group of patients originally receiving BAT. There was a 33 percent reduction in risk of death with ruxolitinib (HR, 0.67; 95 percent CI, 0.44-1.02; P=.06). The estimated probability of survival at 5 years was 56 percent with ruxolitinib and 44 percent with patients originally receiving BAT. At week 48, BAT patients were allowed to cross over to receive ruxolitinib upon protocol-defined progression and after week 48 all BAT patients, irrespective of their progression status, were allowed to crossover to receive ruxolitinib; therefore, a confounding effect on OS was observed. An analysis correcting for crossover will be presented.

Adverse events (AEs) were consistent with those reported in previous studies of ruxolitinib and there was no increase in the incidence of AEs with longer exposure to treatment.

COMFORT-II is scheduled for presentation as an oral session by Dr. Claire Harrison, Guy’s and St. Thomas’ NHS Foundation Trust, Guy’s Hospital, Saturday, December 5, 2015, 9:30-11:30 AM EST, Room W224.

Results from the RESPONSE Study
The RESPONSE trial is a Phase 3 open-label study evaluating long-term safety and efficacy of ruxolitinib in patients with PV compared to BAT who had an inadequate response to or had unacceptable side effects from HU. The analysis from RESPONSE to be presented at ASH (Free ASH Whitepaper) shows that patients who received ruxolitinib had greater mean reductions in WBC counts compared with BAT or the HU subgroup of the BAT arm, and these reductions were maintained over time. In patients with baseline WBC counts ≥11×109/L, worsening WBC counts were observed in 10.8 percent of patients in the ruxolitinib arm versus 35.4 percent in the BAT arm (P=0.0002) and 47.8 percent in the HU subgroup (P<0.0001). In this same subgroup of patients with elevated WBC counts at baseline, a greater proportion of patients in the ruxolitinib arm (45%) normalized their WBC counts (achieving a WBC ≤10×109/L or a ≥50% reduction from baseline) compared with BAT (22%) or HU (9%) at week 32. The median time to achieve this response with ruxolitinib therapy was 8 weeks.

These data are scheduled for presentation as a poster session by Dr. Carole Miller, Saint Agnes Cancer Institute, Monday, December 7, 2015, 6:00-8:00 PM EST, Hall A.

About Myelofibrosis
MF is part of a group of related rare blood cancers known as myeloproliferative neoplasms (MPNs) where a patient’s bone marrow can no longer produce enough normal blood cells, causing the spleen to enlarge1. As a result, patients with MF may suffer from debilitating symptoms and have a poor quality of life2. After diagnosis, patients with MF have a decreased life expectancy, with an average survival of approximately five to six years3. Although allogeneic stem cell transplantation may cure MF, the procedure is associated with significant morbidity and transplant-related mortality, and is available to less than 5% of patients who are young and fit enough to undergo the procedure4.

About Polycythemia Vera
Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) and is typically characterized by elevated hematocrit, the volume percentage of red blood cells in whole blood, which can lead to a thickening of the blood and an increased risk of blood clots, as well as an elevated white blood cell and platelet count5. Patients with PV who fail to consistently maintain appropriate blood count levels, including appropriate hematocrit levels, have an approximately four times higher risk of major thrombosis (blood clots) or cardiovascular death6. Patients with PV can also suffer from an enlarged spleen and a significant symptom burden which may be attributed to thickening of the blood and lack of oxygen to parts of the body7. These symptoms commonly include fatigue, itching, night sweats, bone pain, fever, and weight loss8.

Approximately 100,000 patients in the U.S. are living with PV9. Current standard treatment for PV is phlebotomy (the removal of blood from the body) plus aspirin. When phlebotomy can no longer control PV, chemotherapy such as hydroxyurea, or interferon, is utilized10,11. Approximately one in four patients with PV are considered uncontrolled12,13 because they have an inadequate response to or are intolerant of hydroxyurea, the most commonly used chemotherapeutic agent for the treatment of PV.

About Jakafi (ruxolitinib)

Jakafi is a first-in-class JAK1/JAK2 inhibitor approved by the U.S. Food and Drug Administration, for treatment of people with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea.

Jakafi is also indicated for treatment of people with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF, and post–essential thrombocythemia MF.

Jakafi is marketed by Incyte in the United States and by Novartis as Jakavi (ruxolitinib) outside the United States.

Important Safety Information

Jakafi can cause serious side effects, including:
Low blood counts: Jakafi may cause your platelet, red blood cell, or white blood cell counts to be lowered. If you develop bleeding, stop taking Jakafi and call your healthcare provider. Your healthcare provider will perform blood tests to check your blood counts before you start Jakafi and regularly during your treatment. Your healthcare provider may change your dose of Jakafi or stop your treatment based on the results of your blood tests. Tell your healthcare provider right away if you experience unusual bleeding, bruising, fatigue, shortness of breath, or a fever.

Infection: You may be at risk for developing a serious infection during treatment with Jakafi. Tell your healthcare provider if you develop any of the following symptoms of infection: chills, nausea, vomiting, aches, weakness, fever, painful skin rash or blisters.
Skin cancers: Some people who take Jakafi have developed certain types of non-melanoma skin cancers. Tell your healthcare provider if you develop any new or changing skin lesions.

The most common side effects of Jakafi include: anemia, low platelet count, bruising, dizziness, headache.
These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. Tell your healthcare provider about any side effect that bothers you or that does not go away.

Before taking Jakafi, tell your healthcare provider about all the medications, vitamins, and herbal supplements you are taking and all your medical conditions, including if you have an infection, have or had tuberculosis (TB), or have been in close contact with someone who has TB, have or had liver or kidney problems, are on dialysis, had skin cancer or have any other medical condition. Take Jakafi exactly as your healthcare provider tells you. Do not change or stop taking Jakafi without first talking to your healthcare provider. Do not drink grapefruit juice while on Jakafi.

Women should not take Jakafi while pregnant or planning to become pregnant, or if breast-feeding.

Full Prescribing Information, including a more complete discussion of the risks associated with Jakafi, is available at www.jakafi.com.

On December 5, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported updated data from the pivotal CLL11 study confirming that Gazyva/Gazyvaro (obinutuzumab) plus chlorambucil reduced the risk of disease worsening or death by more than half compared to MabThera/Rituxan (rituximab) plus chlorambucil (progression-free survival, PFS; HR=0.46, median PFS 28.7 months versus 15.7 months; p<0.0001) (Press release, Hoffmann-La Roche , DEC 5, 2015, View Source [SID:1234508417]). New results to be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting from a secondary endpoint that measured time to next treatment (TTNT) showed that, after completing the set six-month Gazyva/Gazyvaro regimen, people remained treatment-free for nearly four years on average before needing the next treatment for their cancer (TTNT; 51.1 months, including the six month initial treatment period). No unexpected safety signals were observed with Gazyva/Gazyvaro.

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"These updated CLL11 data confirmed that Gazyva/Gazyvaro helped people with previously untreated chronic lymphocytic leukaemia live significantly longer without disease worsening or death compared to MabThera/Rituxan," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "After a fixed course of therapy with Gazyva/Gazyvaro, people remained treatment-free for nearly four years on average. Time free from treatment is an important consideration for a disease like CLL, which occurs in older adults who frequently have other health issues. "

In the GREEN safety study, data from a subgroup analysis showed there were no unexpected safety signals when Gazyva/Gazyvaro was combined with bendamustine. In addition, nearly 80 percent of people responded to treatment with Gazyva/Gazyvaro plus bendamustine (overall response, ORR), and a third of people (32.3 percent) achieved a complete response (CR). A substantial number of people were also minimal residual disease (MRD) negative when measured in the bone marrow or blood (28 percent and 59 percent, respectively), which means no cancer can be detected using a specific test. Overall response rate and MRD were secondary endpoints of the study.

Gazyva/Gazyvaro in combination with chlorambucil is approved in the United States for use in people with previously untreated CLL and in the EU for use in people with previously untreated CLL who have comorbidities making them unsuitable for an intensive therapy (full-dose fludarabine based therapy).

About the CLL11 study
CLL11 is a Phase III, multicentre, open-label, randomised three-arm study investigating the efficacy and safety profile of Gazyva/Gazyvaro plus chlorambucil, MabThera/Rituxan plus chlorambucil and chlorambucil alone in 781 people with previously untreated CLL. Stage 1a (n=589) compared Gazyva/Gazyvaro plus chlorambucil to chlorambucil alone and MabThera/Rituxan plus chlorambucil to chlorambucil alone. Stage 2 (n=663) compared Gazyva/Gazyvaro plus chlorambucil with MabThera/Rituxan plus chlorambucil.

The primary endpoint of the study was PFS and secondary endpoints included overall response rate (ORR), overall survival (OS), complete response rate (CR), response duration, disease free survival (DFS), time to next treatment (TTNT), minimal residual disease (MRD) negativity and safety profile.

The updated analysis from CLL11 will be presented at a poster session on Saturday 5 December at 5:30 pm EST (Abstract #1733).

About the GREEN study
GREEN is an ongoing Phase IIIb safety study. This multicentre, open-label, single-arm study is evaluating the safety and efficacy of Gazyva/Gazyvaro alone or in combination with chemotherapy, including bendamustine, in people with previously untreated or relapsed/refractory CLL. The primary endpoint of the study was safety with secondary endpoints including overall response rate (ORR) and minimal residual disease (MRD) negativity.
The study included a subgroup of people who were previously untreated and who received treatment with Gazyva/Gazyvaro in combination with bendamustine. Data from this subgroup analysis will be presented at an oral presentation on Monday, 7 December at 7:00 am EST (Abstract #493).

About Gazyva/Gazyvaro (obinutuzumab)
Gazyva/Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein found only on B-cells. Gazyva/Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system.
Gazyva/Gazyvaro is currently approved in more than 60 countries in combination with chlorambucil, for people with previously untreated CLL. The approval was based on the CLL11 study, showing significant improvements with Gazyva/Gazyvaro plus chlorambucil across multiple clinical endpoints, including progression-free survival (PFS), overall response rate (ORR), complete response rate (CR), and minimal residual disease (MRD) when compared head-to-head with MabThera/Rituxan plus chlorambucil.
Gazyva is marketed as Gazyvaro in the EU and Switzerland.

Gazyva/Gazyvaro is being studied in a large clinical programme, including the Phase III GOYA and GALLIUM studies. GOYA is comparing Gazyva/Gazyvaro head-to-head with MabThera/Rituxan plus CHOP chemotherapy in first line diffuse large B-cell lymphoma (DLBCL) and GALLIUM is comparing Gazyva/Gazyvaro plus chemotherapy followed by Gazyva/Gazyvaro maintenance head-to-head with MabThera/Rituxan plus chemotherapy followed by MabThera/Rituxan maintenance in first line indolent non-Hodgkin’s Lymphoma (NHL). Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are planned or underway across a range of blood cancers.

About CLL
CLL is the most common type of leukaemia in the Western world. It accounts for 25-30% of all leukaemias1, equating to over 80,000 cases of CLL being diagnosed each year2.

On December 5, 2015 Dynavax Technologies Corporation (NASDAQ: DVAX) reported clinical data from an ongoing Phase 1/2 clinical trial evaluating intratumoral administration of SD-101 in the treatment of low-grade lymphoma (Press release, Dynavax Technologies, DEC 5, 2015, View Source [SID:1234508416]). The combination of intratumoral SD-101 and low-dose irradiation resulted in tumor regression in untreated tumor sites as well as in the treated tumors. Treatment was well-tolerated and changes in T cell populations consistent with stimulation of anti-tumor immunity were observed in the treated lesions. These data were presented in a poster session on Saturday at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, Florida.

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Data from the dose escalation phase of the study were reported from 13 evaluable patients. None of the patients had received prior treatment for their low-grade lymphoma. The primary endpoints of the trial are maximum tolerated dose (MTD) and evaluation of the safety of intratumoral SD-101 in combination with low dose radiotherapy. In addition, the trial is evaluating anti-tumor activity, pharmacodynamics, and duration of response. Doses ranged from 1 mg to 8 mg per injection in successive cohorts.

Key findings presented include:

Of the 13 evaluable patients treated across all dose levels, 11 patients (84.6%) were observed to have regression of non-treated, non-irradiated tumors at Day 90 (reductions range from 0.9% to 48.2 %), indicating abscopal effect. One patient reached a partial response (PR) per Cheson criteria at Day 180.

There were no dose limiting toxicities (DLT) and an MTD was not identified. The most common treatment-related adverse events were local injection site reactions and flu-like symptoms, including fever, chills, and myalgia. There have been no serious adverse events related to the treatment.

T cells increased at the treated site in 7 of 10 patients ranging from > 300% to 18%. Both CD4 and CD8 T cells increased in 5 of 7 patients. In addition, TReg cells were depleted at the treated site an average of 22.3 + 9.5% in 8 of 10 patients. Tfh cells showed a significant reduction of 83.3 + 9.9%.

"The first report of clinical responses and changes in T cell populations presented today provide encouraging evidence that immune modulating therapies such as SD-101 can be delivered directly into a tumor to promote changes in the tumor microenvironment and induce a systemic anti-tumor immune response. We look forward to providing future updates as this study and other studies evaluating SD-101 in combination with checkpoint blockade progress," said Eddie Gray, Chief Executive Officer of Dynavax.

To see the poster presentation in its entirety, please visit the Presentations section located in the Investor section of the Dynavax website.

About SD-101

SD-101, the subject of ASH (Free ASH Whitepaper) abstract 1539, is Dynavax’s proprietary, second-generation, TLR 9 agonist CpG-C class oligodeoxynucleotide. SD-101 activates multiple anti-tumor activities of innate immune cells and activates plasmacytoid dendritic cells to stimulate T cells specific for antigens released from dying tumor cells. TLR9 agonists such as SD-101 enhance T and B cell responses and provide potent Type 1 interferon induction and maturation of plasmacytoid dendritic cells to antigen-presenting cells. SD-101 is being evaluated in several Phase 1/2 oncology studies to assess its preliminary safety and activity.