Eli Lilly’s CYRAMZA (Ramucirumab) first FDA approval for Advanced Gastric Cancer

 Eli Lilly and Company (NYSE: LLY) announced today that the U.S. Food and Drug Administration (FDA) has approved CYRAMZA™ (ramucirumab) as a single-agent treatment for patients with advanced or metastatic gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy. With this approval, CYRAMZA becomes the first FDA-approved treatment for patients in this setting.

« Lilly Oncology is committed to delivering innovative medicines that extend the lives of people with cancer, » said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. « Until now, there were no FDA-approved options for patients in this indication. We are pleased that the FDA has approved CYRAMZA for these patients. This is an aggressive disease that is difficult to treat, and the prognosis has typically been very poor. »

The CYRAMZA (ramucirumab injection 10 mg/mL solution) approval is based on results of REGARD, a multicenter, randomized, placebo-controlled, double-blind trial of patients with locally advanced or metastatic gastric cancer including GEJ adenocarcinoma previously treated with fluoropyrimidine- or platinum-containing chemotherapy. It is the first Phase III trial to show improved overall survival and progression-free survival with a biologic agent in advanced gastric cancer after prior chemotherapy. Results demonstrated that CYRAMZA (8 mg/kg by infusion every two weeks) plus best supportive care (BSC), as compared to placebo plus BSC, increased the median overall survival of patients with advanced gastric cancer by 37 percent (median overall survival of 5.2 months [95% confidence interval (CI) 4.4, 5.7] vs. 3.8 months [95% CI 2.8, 4.7] for placebo, P=0.047, hazard ratio 0.78 [95% CI 0.60, 0.998]). Additionally, CYRAMZA significantly improved progression-free survival, demonstrating a 62 percent increase in median progression-free survival (2.1 months [95% CI 1.5, 2.7] vs. 1.3 months [95% CI 1.3, 1.4] for placebo, P < 0.001, hazard ratio 0.48 [95% CI 0.38, 0.62]).

The labeling for CYRAMZA contains a Boxed Warning regarding increased risk of hemorrhage, including severe and sometimes fatal events. CYRAMZA should be discontinued in patients who experience severe bleeding. The most commonly reported adverse reactions (all grades) in REGARD, occurring in at least 5 percent of patients receiving CYRAMZA and at a rate at least 2 percent higher than those receiving placebo, were hypertension (16% vs. 8%), diarrhea (14% vs. 9%), headache (9% vs. 3%), and hyponatremia (6% vs. 2%). The most common serious adverse events with CYRAMZA were anemia (3.8%) and intestinal obstruction (2.1%). Red blood cell transfusions were given to 11% of CYRAMZA-treated patients vs. 8.7% of patients who received placebo. Across clinical trials of CYRAMZA administered as a single agent, clinically relevant adverse reactions (including Grade greater than or equal to 3) reported in CYRAMZA-treated patients included proteinuria, gastrointestinal perforation, and infusion-related reactions. In REGARD, according to laboratory assessment, 8% of CYRAMZA-treated patients developed proteinuria versus 3% of placebo-treated patients. Two patients discontinued CYRAMZA due to proteinuria. The rate of gastrointestinal perforation in the REGARD trial was 0.8% and the rate of infusion-related reactions was 0.4%. This is not a complete list of adverse reactions. For full safety information, see the Important Safety Information at the end of this press release and the full Prescribing Information.

« There is a high unmet medical need in patients with this disease, » said Charles Fuchs, M.D., M.P.H., principal investigator of the REGARD trial and director, Gastrointestinal Malignancy Program,Dana-Farber Cancer Institute. « This approval represents a meaningful advance for patients and gives those of us who treat them an important new second-line treatment option. »

« As someone who has experienced firsthand the limited options available to treat this devastating disease, I consider this approval to be much needed. This is a significant moment for many patients and their families, » said Debbie Zelman, president and founder of a leading international patient advocacy organization, Debbie’s Dream Foundation, which is dedicated to raising awareness about gastric cancer, advancing funding for research, and providing education and support to those affected by the disease. Zelman founded the organization following her own gastric cancer diagnosis. Lilly Oncology and Debbie’s Dream Foundation have established a partnership to improve patient and caregiver awareness of and access to gastric cancer resources.

CYRAMZA is a vascular endothelial growth factor (VEGF) Receptor 2 antagonist that specifically binds VEGF Receptor 2 and blocks binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D. VEGF Receptor 2 is an important mediator in the VEGF pathwayi,ii. In an in vivo animal model, ramucirumab inhibited angiogenesis. Angiogenesis is a process by which new blood vessels form to supply blood to normal healthy tissues as well as tumors, enabling the cancer to grow.

FDA approval of CYRAMZA marks a pivotal regulatory milestone in Lilly’s research and development program for the molecule, which it acquired when it purchased ImClone Systems in 2008. CYRAMZA has been granted Orphan Drug Designation by the FDA for this indication. Orphan drug status is given in the U.S. by the FDA’s Office of Orphan Products Development (OOPD) to medicines that show promise for the treatment of rare diseases. Lilly expects to make CYRAMZA available in the coming weeks and is committed to offering patient assistance programs for eligible patients receiving CYRAMZA treatment.

Source Eli Lilly

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Ipsen announces at ASCO GI that ELECT® clinical trial of Somatuline® in the control of symptoms in GEP-NET1 patients with carcinoid syndrome met its primary endpoint

Results of ELECT® phase III study showed that treatment with  Somatuline® resulted in a statistically significant reduction in the
number of days of rescue medication use versus placebo during the 16-week double-blind phase of the study

Safety data generated are consistent with known safety profile of Somatuline®

Ipsen announced that the results of the ELECT® phase III clinical study with Somatuline® Autogel® / Somatuline® Depot®
(lanreotide) Injection (hereafter referred to as Somatuline®)
Results of the ELECT® phase III study (poster 268) showed that treatment with Somatuline® 120 mg versus placebo resulted in a statistically significant reduction in the number of days in which immediate release octreotide was used as rescue medication, representing a mean difference of -14.8% (95%CI: -26.8, -2.8; p = 0.017). Somatuline® significantly improved the rates of complete/partial treatment success versus placebo (odds ratio = 2.4; 95%CI: 1.1, 5.3; p = 0.036).

Safety data collected during ELECT® study was consistent with known safety profile of Somatuline®.  Somatuline® is approved for the treatment of symptoms associated with carcinoid syndrome in  patients with neuroendocrine tumors in many markets worldwide; it is marketed as Somatuline®  Autogel®, but not in the US, where it is marketed as Somatuline® Depot® for acromegaly only. As such, data arising from the ELECT® study can be considered as an investigational use of Somatuline®
Depot® in the United States.

Claude Bertrand, Executive Vice-President, Research & Development and Chief Scientific Officer of Ipsen stated: “The results observed in the multinational ELECT® study add to the body of evidence evaluating the efficacy and safety of Somatuline® in the control of symptoms in GEP-NET patients with carcinoid syndrome. Along with the recently reported CLARINET® results demonstrating the antiproliferative effect of Somatuline®, ELECT results represent new data to document the efficacy  and safety of Somatuline® in gastroenteropancreatic neuroendocrine tumors.”

Edward M. Wolin, MD, Co-Director, Carcinoid and Neuroendocrine Tumor Program Medical Oncology, Samuel Oschin Cancer Center, Cedars-Sinai (USA) stated: “In the ELECT® study, rescue medication with immediate release formulation of octreotide was allowed for all patients in the Somatuline® and placebo arms when needed to control their symptoms. This study demonstrated a decreased use of octreotide as rescue medication in patients treated with Somatuline® 120mg when compared to those receiving placebo (both naïve to treatment or previously treated with a somatostatin analogue).”

Source: Ipsen

Pfizer And GSK To Initiate Study Of Novel Combination Therapy In Patients With Melanoma

Pfizer Inc. announced that it has entered into an agreement with GSK to explore the anti-cancer efficacy and the safety of GSK’s trametinib (GSK1120212) combined with Pfizer’s palbociclib (PD-0332991) in a Phase I/II study (Study 200344) in patients with advanced/metastatic melanoma.

Study 200344 is a dose-escalation, open-label study designed to determine the recommended combination regimen (RCR) for trametinib plus palbociclib in patients with melanoma.  The study will also evaluate the effect of the combination on tumor biomarkers, safety and anti-cancer activity in patients with BRAFV600 wild type melanoma, including those with NRAS mutations.

“Pfizer Oncology is committed to maximizing the value of our portfolio for patients through the study of novel combinations.  This includes combining our own cancer medicines with each other, as well as with those of other companies where there is strong scientific rationale,” said Garry Nicholson, president and general manager, Pfizer Oncology Business Unit.  “Emerging data suggest the potential for trametinib and palbociclib to work together to treat melanoma.  We look forward to collaborating with GSK to explore this potential and evaluate the clinical activity of this combination in melanoma.”

The two companies will collaborate on the study, which GSK will conduct.  Financial terms of the agreement were not disclosed.

Trametinib, a reversible inhibitor of MEK1 and MEK2, is approved by the U.S. Food and Drug Administration (FDA) under the name Mekinist® for the treatment of adult patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutation as detected by an FDA-approved test.  Mekinist is not indicated for the treatment of patients who have received a prior BRAF inhibitor therapy.

Palbociclib is an investigational oral and selective inhibitor of cyclin dependent kinases (CDK) 4 and 6.  In April 2013, palbociclib received Breakthrough Therapy designation by the FDA for the potential treatment of patients with breast cancer. Palbociclib is not approved for any indication in any markets.

Source: Pfizer

FDA clears Bayer, Onyx Pharmaceuticals’ Nexavar for late-stage differentiated thyroid cancer

The FDA on Friday approved Bayer and Onyx Pharmaceuticals’ Nexavar (sorafenib) for the treatment of patients with late-stage differentiated thyroid cancer. Pamela A. Cyrus, head of US medical affairs for Bayer, remarked « Nexavar is the first and only FDA-approved therapy for this type of thyroid cancer and is a positive development for patients who previously had limited treatment options. »

The approval was supported by a study involving 417 patients with radioactive iodine-refractory locally recurrent or metastatic, progressive differentiated thyroid cancer. Study data showed that the therapy extended progression-free survival by 41 percent, as patients treated with Nexavar displayed a progression-free survival of 10.8 months, versus 5.8 months for the placebo arm.

Nexavar gained expanded US approval for the treatment of late-stage differentiated thyroid cancer under the FDA’s priority reviewprogramme. The drug was previously approved for the treatment of advanced kidney cancer and for advanced liver cancer.

Onyx was acquired by Amgen earlier this year for $10.4 billion, granting the latter rights to Nexavar.

Roche’s Kadcyla approved in the EU for advanced HER2-positive breast cancer

Roche announced that Kadcyla (trastuzumab emtansine or T-DM1), the latest targeted medicine from its HER2 franchise and its first antibody-drug conjugate, has been approved by the European Commission for people with previously treated HER2-positive advanced breast cancer.

Specifically, Kadcyla is indicated as a single agent for the treatment of adults with HER2-positive, unresectable locally advanced or metastatic breast cancer who previously received Herceptin (trastuzumab) and a taxane, separately or in combination. The indication also stipulates that those treated should either have received prior therapy for locally advanced or metastatic disease, or have had disease recurrence during or within six months of completing adjuvant therapy.

“Kadcyla’s approval in the EU is important because this type of targeted medicine has been shown in clinical studies to offer clear benefits for people with advanced HER2-positive breast cancer,” said Hal Barron, M.D., Roche’s Chief Medical Officer and Head of Global Product Development. “Now that Kadcyla has been approved, we can begin discussions with the relevant EU reimbursement authorities to ensure that people who need this medicine can receive it as quickly as possible. »

The decision is based on results from the pivotal Phase III EMILIA study in which people previously treated with Herceptin and a taxane for their HER2-positive advanced breast cancer were randomised to receive either Kadcyla or a standard treatment, lapatinib and Xeloda (capecitabine). People receiving Kadcyla survived significantly longer than those who received lapatanib and Xeloda (30.9 vs 25.1 months) and also lived for nearly 10 months (9.6 months) without their disease getting worse, a median of 3.2 months longer than those who received lapatinib and Xeloda. They also experienced fewer of the severe side effects commonly associated with chemotherapy, as Kadcyla’s targeted mode of action works to deliver the treatment directly to cancer cells, limiting damage to healthy tissues.

 

Source: Roche

Roche Cancer Vaccine Pact Could Net Immatics $1B

Roche will oversee clinical development and commercialization of all immunotherapies generated by immatics biotechnologies under a cancer vaccine and immunotherapy collaboration that could net the German clinical-stage biopharma more than $1 billion.

Roche agreed to pay immatics $17 million up-front and additional unspecified committed research funding, plus more than $1 billion in milestone payments and royalties across three cancer indications, to be based on sales of the cancer vaccines and immunotherapies resulting from the companies’ collaboration.

The collaboration will focus on research, clinical development, and commercialization of a number of new tumor-associated peptide (TUMAP)-based cancer vaccine candidates and other immunotherapies in oncology, targeting primarily gastric, prostate, and non-small cell lung cancer. Furthest along in development among the candidates is IMA942, for gastric cancer, which according to the companies is ready for Phase I trials.

Also as part of the collaboration, immatics will use its XPRESIDENT® technology platform to identify TUMAP candidates for development of cancer vaccines and other compounds targeting cancer peptide antigens, primarily in gastric, prostate, and non-small cell lung cancer. According to the companies, XPRESIDENT is the only known high-throughput research technology capable of directly identifying, quantifying, and prioritizing cancer antigens recognized by T lymphocytes based on the ability of the immune system to detect them.

“The wealth of relevant cancer-specific antigens that we expect to emerge from this research collaboration will provide an extraordinary opportunity to elicit broad tumor-specific immune responses upon vaccination, especially when combined with other immunomodulatory molecules in our pipeline,” Hy Levitsky, Roche’s head of cancer immunology experimental medicine, said in a statement. “Discovery of novel antigens also will provide unique targets for other protein-based anti-cancer agents currently under development.”

immatics’ collaboration with Roche comes about a month after the company won €34 million ($46 million) in Series D financing—of which €12 million ($16 million) will be received immediately—to conclude development of its lead vaccine IMA901, now in a Phase III trial, including completing all activities needed to prepare for regulatory filings in the United States and Europe.

IMA901 is a cancer vaccine consisting of 10 TUMAPs found to be highly overexpressed in the majority of patients suffering from renal cell carcinoma (RCC). The vaccine has U.S. and European orphan drug designations for treating RCC in HLA-A*02 positive patients. The Phase III trial is designed to evaluate overall survival with IMA901 in combination with Pfizer ‘s Sutent® (sunitinib), the current standard first-line therapy, compared with sunitinib alone in patients with metastatic and/or locally advanced RCC. A total of 339 patients are enrolled in the trial, which is expected to generate interim overall survival results in 2014, with final data in 2015.

Source : genengnews

FDA approves Roche’s Gazyva (obinutuzumab) for people with previously untreated chronic lymphocytic leukemia (CLL)

Gazyva demonstrated an 84 percent reduction in the risk of disease worsening or death when combined with chemotherapy compared to chemotherapy alone
Gazyva is the first medicine approved with the FDA’s Breakthrough Therapy Designation
Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the U.S. Food and Drug Administration (FDA) approved Gazyva (obinutuzumab), also known as GA101, in combination with chlorambucil chemotherapy for the treatment of people with previously untreated chronic lymphocytic leukemia (CLL). Gazyva is the first medicine approved with the FDA’s Breakthrough Therapy Designation and the fifth cancer medicine from Roche approved by the FDA in the past three years.
“Gazyva is an important new medicine for people with newly diagnosed chronic lymphocytic leukemia as based on clinical data, it more than doubled the time people lived without their disease worsening compared to chlorambucil alone,” said Hal Barron, M.D., chief medical officer and head of Global Product Development. “We have spent 20 years researching blood cancer medicines, and we will continue to study Gazyva to assess its efficacy in other types of blood cancers.”
The FDA granted Gazyva Breakthrough Therapy Designation due to the significance of the positive progression-free survival (PFS) results from the Phase III CLL11 trial and the serious and life-threatening nature of CLL.
Today’s FDA approval is based on the outcomes of the CLL11 trial. The trial showed that people who received Gazyva in combination with chlorambucil chemotherapy had significantly reduced risk of disease progression or death (HR=0.16; p<0.0001) and lived significantly longer without their disease getting worse compared to those who received chlorambucil alone (median PFS 23.0 months vs. 11.1 months). The most common Grade 3/4 adverse events for those who received Gazyva in combination with chlorambucil compared to chlorambucil alone were infusion-related reactions during the first infusion (21 percent vs. 0 percent [chlorambucil is an oral medicine]), low platelet count (thrombocytopenia, 11 percent vs. 3 percent) and low count of certain types of white blood cells (neutropenia, 34 percent vs. 16 percent), though this did not result in an increased rate of infections in the Gazyva arm.
Final data from the CLL11 trial investigating the direct comparison between Gazyva in combination with chlorambucil and MabThera/Rituxan (rituximab) in combination with chlorambucil (Stage 2), will be presented at the American Society of Hematology’s (ASH) 55th Annual Meeting in December 2013
Marketing applications have also been submitted to other regulatory authorities, including the European Medicines Agency (EMA).

About Chronic Lymphocytic Leukemia (CLL)
CLL is one of the most common forms of blood cancer and in 2013, it is expected that there will be nearly 5,000 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 a new 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 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 now approved in combination with chlorambucil for people with previously untreated chronic lymphocytic leukemia (CLL) and is additionally being investigated in a large clinical programme, including multiple head-to-head Phase III studies compared to MabThera/Rituxan in indolent non-Hodgkin lymphoma (NHL) and diffuse large B-cell lymphoma (DLBCL).

Gazyva Efficacy in CLL
The pivotal Phase III CLL11 trial, conducted in cooperation with the German CLL Study Group (GCLLSG), is a multicentre, open-label, randomised three-arm study investigating the efficacy and safety profile of either Gazyva plus chlorambucil or MabThera/Rituxan plus chlorambucil compared to chlorambucil alone in 781 previously untreated people with CLL and co-existing medical conditions.
The study showed that Gazyva demonstrated a statistically significant 84 percent reduction in the risk of disease worsening or death (PFS; HR=0.16, 95 percent CI 0.11-0.24, p<0.0001) when combined with chlorambucil compared to chlorambucil alone in people with previously untreated CLL and co-existing medical conditions. In the CLL11 study, no new safety signals were detected for Gazyva.
Gazyva in combination with chlorambucil more than doubled the time people with newly diagnosed CLL lived without their disease getting worse (median PFS: 23.0 vs. 11.1 months).
75.9 percent of people responded to Gazyva in combination with chlorambucil (overall response rate, or ORR) compared to 32.1 percent with chlorambucil alone.
More than a quarter of the people who received Gazyva in combination with chlorambucil achieved a complete response (CR: 27.8 percent vs. 0.9 percent).

About Roche in hematology

For more than 20 years, Roche has been developing medicines that redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with cancers of the blood.
In addition to Gazyva, Roche’s pipeline of potential hematology medicines includes two antibody-drug conjugates (anti-CD79b [RG7596] and anti-CD22 [RG7593]), a small molecule antagonist of MDM2 (RG7112) and in collaboration with AbbVie, a small molecule BCL-2 inhibitor (RG7601/GDC-0199/ABT-199).

Source: Roche