1stOncology™: Cancer Intelligence Service – Page 16948 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Amgen Receives CHMP Positive Opinion For IMLYGIC™ (Talimogene Laherparepvec)

On October 23, 2015 Amgen (NASDAQ:AMGN) reported that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), has adopted a positive opinion recommending that IMLYGIC (talimogene laherparepvec) be granted approval for the treatment of adults with unresectable melanoma that is regionally or distantly metastatic (Stage IIIB, IIIC and IVM1a) with no bone, brain, lung or other visceral disease (Press release, Amgen, OCT 23, 2015, View Source [SID:1234507773]). If approved by the European Commission, IMLYGIC would be the first in a class of novel agents known as oncolytic immunotherapies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

IMLYGIC, administered via intralesional injection, is designed to cause the death of tumor cells and to initiate an anti-tumor immune response.

"We are pleased that IMLYGIC has received a positive opinion from the CHMP, and if approved by the European Commission, we look forward to continuing to work with European regulatory authorities to bring this innovative therapy to patients," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Metastatic melanoma continues to be one of the most difficult-to-treat cancers, often requiring the use of multiple treatment modalities. Despite recent advances, the five-year survival rate for patients who cannot be cured with surgery remains unacceptably low, demonstrating the critical need for additional approaches to control this disease."

The positive CHMP opinion was based on a global, randomized, open-label Phase 3 trial evaluating the safety and efficacy of IMLYGIC in patients with Stage IIIB, IIIC or IV melanoma when resection was not recommended compared to granulocyte-macrophage colony-stimulating factor (GM-CSF). In the 436-patient study, IMLYGIC significantly improved durable response rate (DRR), the primary endpoint of the trial, in the intent-to-treat population. DRR is defined as the percent of patients with complete response (CR) or partial response (PR) maintained continuously for a minimum of six months. A key secondary endpoint was overall survival (OS). The positive CHMP opinion reflects subgroup analyses where the effect on OS was largest in patients with unresectable melanoma that has not spread beyond the skin or lymph nodes.

The most commonly reported treatment-related adverse events were fatigue, chills, pyrexia, nausea, influenza-like illness and injection-site pain. Overall, 98 percent of these adverse reactions reported were mild or moderate in severity. The most common grade 3 or higher adverse reaction was cellulitis.

Melanoma is a type of skin cancer that is characterized by the uncontrolled growth of melanocytes, which are the cells responsible for providing the pigment to skin.1 Melanoma is the most aggressive and serious form of skin cancer, and remains a significant public health concern in the European Union (EU).2,3 In 2012, it was estimated that there were 56,000 new cases of melanoma in France, Italy, Spain, Germany and the U.K. causing nearly 9,500 deaths.4,5

Following this CHMP opinion, Amgen expects a decision on the Marketing Authorization from the European Commission in the coming months. IMLYGIC is also under review by the U.S. Food and Drug Administration.

About IMLYGIC (talimogene laherparepvec) in the EU

IMLYGIC is an oncolytic immunotherapy that is derived from HSV-1, which is commonly called the cold sore virus. IMLYGIC has been modified to replicate within tumors and to produce the immune stimulatory protein human GM-CSF. IMLYGIC causes the death of tumor cells and the release of tumor-derived antigens. It is thought that, together with GM-CSF, it will promote a systemic anti-tumor immune response and an effector T cell response.

About IMLYGIC (talimogene laherparepvec) in the U.S.

IMLYGIC is a genetically modified herpes simplex type 1 virus that is injected directly into tumors. IMLYGIC replicates inside tumor cells and produces GM-CSF, an immunostimulatory protein. IMLYGIC then causes the cell to rupture and die in a process called lysis. The rupture of the cancer cells causes the release of tumor-derived antigens, which together with virally derived GM-CSF may help to promote an anti-tumor immune response. However, the exact mechanism of action is unknown.

Spectrum Pharmaceuticals Receives Complete Response Letter (CRL) from U.S. Food and Drug Administration (FDA) for EVOMELA™ (melphalan) for Injection

On October 23, 2015 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported that it has received a Complete Response Letter from the U.S. Food and Drug Administration (FDA) (Press release, Spectrum Pharmaceuticals, OCT 23, 2015, View Source [SID:1234507771]). A Complete Response Letter is a communication from the FDA that informs companies that an application cannot be approved in its present form. In the letter, the FDA did not identify any clinical deficiency in Spectrum’s NDA package.

"We will work swiftly with the FDA to address the Complete Response Letter," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "We remain committed to bringing EVOMELA to the market for patients and plan to work closely with the FDA."

Spectrum Pharmaceuticals gained global development and commercialization rights to EVOMELA from Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) in March 2013. Spectrum assumed responsibility for completing the pivotal Phase 2 clinical trial, and was responsible for filing the NDA. Under the license agreement, Ligand received a license fee and is eligible to receive milestone payments, as well as royalties following potential commercialization.

On October 22, 2015, Roche Holding AG ("Roche") disclosed that its GATSBY trial assessing its product, Kadcyla (ado-trastuzumab emtansine), for second-line treatment of HER2-positive advanced gastric cancer did not meet its primary endpoint (Filing, 8-K, ImmunoGen, MAY 22, 2015, View Source [SID:1234512502]). Roche expects the detailed clinical findings from GATSBY to be reported at a future medical conference. Earlier this year, ImmunoGen, Inc. entered into a royalty purchase agreement that monetized the Company’s royalties on Kadcyla sales.

Moderna Launches Caperna LLC, Its Fourth Venture, to Develop Personalized Cancer Vaccines

On October 22, 2015 Moderna Therapeutics, a pioneer in the development of messenger RNA (mRNA) Therapeutics, reported the launch of Caperna LLC, the fourth Moderna venture, which will focus exclusively on the advancement of personalized cancer vaccines.

Caperna will apply Moderna’s mRNA vaccine technology to the field of cancer vaccines, building on advances in recent years in cancer immunotherapy, including the availability of checkpoint inhibitors and the ability to rapidly determine individual patient mutations. Caperna will develop personalized cancer vaccines that encode a patient’s specific neoepitopes, utilizing Moderna’s unique infrastructure to manufacture within weeks small batches of vaccines tailored to each patient.

Substantial efforts at Moderna’s infectious disease venture Valera have demonstrated preclinical efficacy of Moderna’s mRNA-based vaccines in multiple viral disease models, which has led to the nomination of several viral vaccine development candidates. These advancements have spurred the formation of Caperna and the pursuit of vaccine development for the treatment of cancer.

Tal Zaks, M.D., Ph.D., Chief Medical Officer of Moderna, who was formerly Senior Vice President and Head of Global Oncology at Sanofi, will serve as Interim President of Caperna. Nicholas Valiante, Ph.D., who recently joined Moderna from Novartis Vaccines where he was Global Head of Immunology & Immunotherapy Research, will serve as Vice President and Head of Personalized Vaccine Sciences.

"With such a potent vaccine platform and a manufacturing process that lends itself directly to rapid production of patient-specific therapies, we believe Moderna’s mRNA approach will offer distinct advantages in the development of new cancer therapies," said Dr. Zaks. "We expect our ability to specifically activate and direct the immune system will synergize with checkpoint inhibitor therapies like PD-1 antibodies."

"What is perhaps most exciting about our approach and our core protein expression platform is its potential to leverage a broad spectrum of leading-edge drug modalities," said Stéphane Bancel, Chief Executive Officer of Moderna. "Caperna is an important example of Moderna’s unique ability to rapidly translate our ever-evolving understanding of mRNA into new therapeutic opportunities that have the potential to impact and change numerous lives. Caperna will be backed by Moderna’s $840 million of cash on hand."

Onkaido, Moderna’s initial oncology venture, remains focused on the development of mRNA-based therapeutics for oncology in areas outside of the personalized cancer vaccine effort at Caperna.

FDA approves new treatment for advanced pancreatic cancer

On October 22, 2015 The U.S. Food and Drug Administration reported it approved Onivyde (irinotecan liposome injection), in combination with fluorouracil and leucovorin, to treat patients with advanced (metastatic) pancreatic cancer who have been previously treated with gemcitabine-based chemotherapy (Press release, , OCT 22, 2015, View Source [SID:1234507767]).
According to the National Cancer Institute, there will be 48,960 new cases of pancreatic cancer diagnosed in the U.S. in 2015, and nearly the same number of deaths caused by the disease (40,560). Pancreatic cancer can be difficult to diagnose early and treatment options are limited, especially when the disease has spread to other parts of the body (metastatic disease) and surgery to remove the tumor is not possible.

"Many FDA staff who review drug applications are clinicians as well, so it’s especially rewarding when we are able to expedite access to new treatments for patients with unmet needs," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. "By using the Priority Review designation for the application for Onivyde, patients will have earlier access to a drug that helps extend survival."

The FDA granted Priority Review and orphan drug designations for Onivyde. Priority review status is granted to applications for drugs that, if approved, would be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as tax credits, user fee waivers, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

The effectiveness of Onivyde was demonstrated in a three-arm, randomized, open label study of 417 patients with metastatic pancreatic adenocarcinoma whose cancer had grown after receiving the chemotherapeutic drug gemcitabine or a gemcitabine-based therapy. The study was designed to determine whether patients receiving Onivyde plus fluorouracil/leucovorin or Onivyde alone lived longer than those receiving fluorouracil/leucovorin. Patients treated with Onivyde plus fluorouracil/leucovorin lived an average of 6.1 months, compared to 4.2 months for those treated with only fluorouracil/leucovorin. There was no survival improvement for those who received only Onivyde compared to those who received fluorouracil/leucovorin.

In addition, patients receiving Onivyde plus fluorouracil/leucovorin had a delay in the amount of time to tumor growth compared to those who received fluorouracil/leucovorin. The average time for those receiving Onivyde plus fluorouracil/leucovorin was 3.1 months compared to 1.5 months for those receiving fluorouracil/leucovorin.

The safety of Onivyde was evaluated in 398 patients who received either Onivyde with fluorouracil/leucovorin, Onivyde alone or fluorouracil/leucovorin. The most common side effects of treatment with Onivyde included diarrhea, fatigue, vomiting, nausea, decreased appetite, inflammation in the mouth (stomatitis) and fever (pyrexia). Onivyde was also found to result in low counts of infection-fighting cells (lymphopenia and neutropenia). Death due to sepsis following neutropenia has been reported in patients treated with Onivyde.

The labeling for Onivyde includes a boxed warning to alert health care professionals about the risks of severe neutropenia and diarrhea. Onivyde is not approved for use as a single agent for the treatment of patients with metastatic pancreatic cancer.

Onivyde is marketed by Merrimack Pharmaceuticals Inc. of Cambridge, Massachusetts.