On April 9, 2015 Inovio Pharmaceuticals reported preliminary data showing that its INO-3112 DNA-based immunotherapy generated strong CD8+ T cell responses in 3 of 4 patients with head and neck cancer associated with human papillomavirus (HPV) types 16 and 18 (Press release, Inovio, APR 9, 2015, View Source;Neck-Cancer-Patients/default.aspx [SID:1234502974]). INO-3112, an active immunotherapy that targets HPV 16 and 18 and simultaneously expresses IL-12, is designed to activate in vivo (in the body) immune responses to antigens from high risk HPV types and eliminate precancerous and cancerous cells displaying these antigens. The data, which are T cell measurements from the first four treated patients of this phase I/IIa study, are being presented today at the World Vaccine Congress 2015 by Inovio’s COO, Dr. Niranjan Y. Sardesai.

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These positive results represent the first study and first report of T cell immune responses generated in cancer patients after treatment with an Inovio DNA immunotherapy. The magnitude and characteristics of these interim immune response data mirror immune responses previously observed in human studies of VGX-3100 for HPV-associated cervical dysplasia; in a placebo-controlled phase II study, strong T cell immune responses were positively correlated with achievement of primary and secondary efficacy endpoints.

Dr. J. Joseph Kim, Inovio’s President and CEO, said, "This initial data set from Inovio’s first cancer study provides encouraging evidence that we are on an important path to better optimized immunotherapy products. Regardless of whether it is an infectious disease, a precancer, or a cancer: the immune system uses the same mechanism to eliminate infected or mutated cells. In immune-oncology, it’s all about the T cells. Here we show in cancer patients that we can generate antigen-specific CD8+ killer T cell responses, which are essential to an effective immunotherapy.

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"We look forward to completing our currently enrolling studies for HPV-associated head & neck and cervical cancers, completing the preparations for our planned phase III study for cervical precancer, and launching new studies for hepatitis B and prostate cancer that all rely on the same targeted T-cell-based killing activity."

This open label study of HPV-caused head and neck cancer is intended to assess the safety, tolerability, and immunogenicity of INO-3112 in up to twenty adults with HPV-positive head and neck squamous cell carcinoma. The study (NCT02163057) includes patients who are being treated with INO-3112 before and after resection of their tumor as well as patients being treated with INO-3112 after completion of chemotherapy and radiation therapy.

About HPV-Caused Head & Neck Cancer

Human papillomavirus (HPV) is the most common sexually transmitted disease in the United States, infecting 79 million Americans. HPV is known to play a major role in the development of head and neck cancers, which include cancers of the oral cavity, oropharynx, nose/nasal passages and larynx. Head and neck cancers associated with HPV account for nearly 3 percent of all cancers in the United States and are twice as prevalent in men as in women. Incidence rates of HPV-caused head and neck cancers have been on the rise, especially HPV-associated oropharyngeal cancer in men, and are expected to continue growing. By 2025, researchers believe that HPV will be the causative factor of 90% of all head/neck cancers.

On April 9, 2015 Exelixis reported that the U.S. Food & Drug Administration (FDA) has granted Fast Track designation to cabozantinib for treatment of patients with advanced renal cell carcinoma (RCC) who have received one prior therapy (Press release, Exelixis, APR 9, 2015, View Source [SID:1234502971]). Cabozantinib is the company’s lead compound and inhibits the activity of multiple tyrosine kinases including MET, VEGFRs and RET. The FDA created the Fast Track process to facilitate the development and expedite the review of drugs to treat serious diseases and address unmet medical needs. Fast Track designation confers important benefits, including the potential eligibility for Priority Review of a New Drug Application, if relevant criteria are met.1

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Cabozantinib is the subject of METEOR, an ongoing phase 3 pivotal trial in patients with metastatic RCC who have experienced disease progression following treatment with at least one VEGFR tyrosine kinase inhibitor. Patients are randomized 1:1 to receive 60 mg of cabozantinib daily or 10 mg of everolimus daily. The primary endpoint of METEOR is progression-free survival, and secondary endpoints include overall survival and objective response rate. Exelixis expects to release top-line results from the trial in the second quarter of 2015. In addition to the metastatic RCC development program, Exelixis is also evaluating cabozantinib in CELESTIAL, a phase 3 pivotal trial in second-line hepatocellular carcinoma (HCC).

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About Metastatic Renal Cell Carcinoma

The American Cancer Society’s 2015 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the United States.2 Clear cell renal cell carcinoma is the most common type of kidney cancer in adults.3 If detected in its early stages, the five-year survival rate for RCC is high; however, the five-year survival rate for patients with advanced or late-stage metastatic RCC is under 10 percent, with no identified cure for the disease.4

Treatments for metastatic RCC had historically been limited to immunotherapy (e.g., interleukin-2 and interferon) until the introduction of targeted therapies into the RCC setting a decade ago. In the second-line setting, which encompasses approximately 11,000 drug-eligible patients in the U.S. and 37,000 globally, four new therapies have been approved in the past five years.5 Despite the availability of several therapeutic options, however, currently approved agents have shown little differentiation in terms of efficacy and have demonstrated only modest PFS benefit in patients refractory to sunitinib, a commonly-used first-line therapy.

About Cabozantinib

Cabozantinib inhibits the activity of tyrosine kinases including MET, VEGFRs and RET. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment.

COMETRIQ (cabozantinib) is currently approved by the U.S. Food and Drug Administration for the treatment of progressive, metastatic medullary thyroid cancer (MTC).

The European Commission granted COMETRIQ conditional approval for the treatment of adult patients with progressive, unresectable locally advanced or metastatic MTC. Similar to another drug approved in this setting, the approved indication states that for patients in whom Rearranged during Transfection (RET) mutation status is not known or is negative, a possible lower benefit should be taken into account before individual treatment decisions.

Important Safety Information, including Boxed WARNINGS

WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE

Serious and sometimes fatal gastrointestinal perforations and fistulas occur in COMETRIQ-treated patients.
Severe and sometimes fatal hemorrhage occurs in COMETRIQ-treated patients.
COMETRIQ treatment results in an increase in thrombotic events, such as heart attacks.
Wound complications have been reported with COMETRIQ.
COMETRIQ treatment results in an increase in hypertension.
Osteonecrosis of the jaw has been observed in COMETRIQ-treated patients.
Palmar-Plantar Erythrodysesthesia Syndrome (PPES) occurs in patients treated with COMETRIQ.
The kidneys can be adversely affected by COMETRIQ. Proteinuria and nephrotic syndrome have been reported in patients receiving COMETRIQ.
Reversible Posterior Leukoencephalopathy Syndrome has been observed with COMETRIQ.
Avoid administration of COMETRIQ with agents that are strong CYP3A4 inducers or inhibitors.
COMETRIQ is not recommended for use in patients with moderate or severe hepatic impairment.
COMETRIQ can cause fetal harm when administered to a pregnant woman.
Adverse Reactions – The most commonly reported adverse drug reactions (≥25%) are diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome (PPES), decreased weight, decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, and constipation. The most common laboratory abnormalities (≥25%) are increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.

Please see full U.S. prescribing information, including Boxed WARNINGS, at www.COMETRIQ.com/downloads/Cometriq_Full_Prescribing_Information.pdf. Please refer to the full European Summary of Product Characteristics for full European Union prescribing information, including contraindication, special warnings and precautions for use at www.sobi.com once posted.

On April 8, 2015 Roche reported that the European Commission (EU) approved Avastin (bevacizumab) in combination with standard chemotherapy (paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in patients who cannot receive platinum therapy) for the treatment of adult patients with persistent, recurrent or metastatic carcinoma of the cervix(Press release, Hoffmann-La Roche , APR 8, 2015, View Source [SID:1234502964]).1

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Unlike the majority of cancers, cervical cancer is most commonly diagnosed in younger women, between the ages of 35 and 44.2 Each day it is estimated that 90 women are diagnosed with cervical cancer in Europe, and around 35 of these women will die from the disease.3 Avastin’s EU approval in persistent, recurrent or metastatic carcinoma of the cervix is an important development in a disease area where, until now, treatment options were limited to chemotherapy.

"We are pleased that women in Europe now have a much needed new treatment option that is proven to help them live longer lives compared to chemotherapy alone," said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. "Currently, fewer than one in six women with this disease are alive five years after diagnosis. Avastin’s approval is a welcome advance for women with persistent, recurrent or metastatic carcinoma of the cervix".

The EU approval was based on the significant survival benefit in the pivotal GOG-0240 study, which showed that women who received Avastin plus chemotherapy had a statistically significant 26 percent reduction in the risk of death, representing a median improvement in survival of nearly four months, compared to women who received chemotherapy alone (median overall survival: 16.8 months vs. 12.9 months; Hazard Ratio (HR)=0.74, p=0.0132).1

Also based on the GOG-0240 data, Avastin in combination with paclitaxel and cisplatin or paclitaxel and topotecan chemotherapy was approved in the U.S. in August 2014, in Switzerland in December 2014, and in six other countries worldwide, for the treatment of women with persistent, recurrent or metastatic carcinoma of the cervix.
About the GOG-0240 study1

GOG-0240 is an independent, National Cancer Institute (NCI)-sponsored study of the Gynecological Oncology Group (GOG) that assessed the efficacy and safety profile of Avastin plus chemotherapy (paclitaxel and cisplatin or paclitaxel and topotecan) in women with persistent, recurrent or metastatic carcinoma of the cervix.

Study data from 452 women showed:

The study met its primary endpoint of improving overall survival (OS) with a statistically significant 26 percent reduction in the risk of death, representing a median gain in survival of 3.9 months, compared with those who received chemotherapy alone (median overall survival: 16.8 months vs. 12.9 months; (HR)=0.74, p=0.0132).1
The study showed that women who received Avastin plus chemotherapy had a significantly higher rate of tumour shrinkage (objective response rate, ORR) compared with those who received chemotherapy alone (45 percent [95% CI: 0.39%-0.52%] vs. 34 percent [95% CI 0.28%-0.40%]).1
Overall, the safety profile in the study was consistent with that seen in previous pivotal studies of Avastin across tumour types, except for an increase in gastrointestinal-vaginal fistulae observed in patients who received Avastin plus chemotherapy compared to those who received chemotherapy alone (8.3% vs. 0.9% respectively). All patients with gastrointestinal-vaginal fistulae after treatment with Avastin plus chemotherapy had a history of prior pelvic radiation.1

About cervical cancer

It is estimated that over 33,000 women will be diagnosed with cervical cancer in the EU this year and about 13,000 women will die from the disease.3 While the chances of survival are higher if the disease is caught early (at least nine out of 10 women survive for five years or longer following early diagnosis), the symptoms of early-stage cervical cancer can be easily missed, and many women are not diagnosed until their cancer has already progressed to an advanced stage.2,4 At this stage, the survival rates are reduced and fewer than one in six women survive for five years or longer.2,4

Worldwide, it is estimated there are more than half a million cases of cervical cancer every year and over 260,000 deaths from the disease, making it the fourth leading cause of cancer death in women globally.5
About Avastin

With the initial approval in the United States for advanced colorectal cancer in 2004, Avastin became the first anti-angiogenic therapy made widely available for the treatment of patients with an advanced cancer.

Today, Avastin is continuing to transform cancer care through its proven survival benefit (overall survival and/or progression free survival) across several types of cancer. Avastin is approved in Europe for the treatment of advanced stages of breast cancer, colorectal cancer, non-small cell lung cancer, kidney cancer, ovarian cancer, and now cervical cancer, and is available in the United States for the treatment of colorectal cancer, non-small cell lung cancer, kidney cancer, cervical cancer and platinum-resistant, recurrent ovarian cancer. In addition, Avastin is approved in the United States and over 60 other countries worldwide for the treatment of patients with progressive glioblastoma following prior therapy. Avastin is approved in Japan for the treatment of the advanced stages of colorectal, non-small cell lung cancer, breast cancer, ovarian cancer and malignant glioma, including newly diagnosed glioblastoma.

Avastin has made anti-angiogenic therapy a fundamental pillar of cancer treatment today. Over 1.5 million patients have been treated with Avastin so far. A comprehensive clinical programme with more than 500 ongoing clinical trials is investigating the use of Avastin in over 50 tumour types.
About Avastin – mechanism of action

An independent blood supply is critical for a tumour to grow beyond a certain size (2mm) and spread (metastasise) to other parts of the body. Tumours develop their own blood supply in a process called angiogenesis by releasing vascular endothelial growth factor (VEGF) – a key driver for tumour growth. Avastin is an antibody that precisely targets and inhibits VEGF. Precise VEGF inhibition by Avastin allows it to be combined effectively with a broad range of chemotherapies and other anti-cancer treatments with limited additional impact on the side effects of these therapies.