On January 23, 2015 Celgene reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for ABRAXANE (paclitaxel formulated as albumin-bound nanoparticles, or nab-paclitaxel) in combination with carboplatin for the first-line treatment of non-small cell lung cancer in adult patients who are not candidates for potentially curative surgery and/or radiation therapy (Press release Celgene, JAN 23, 2015, View Source [SID:1234501378]).

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Lung cancer is the fourth most commonly diagnosed cancer in both men and women, however it is the leading cause of cancer-related mortality in Europe. Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for 85 to 90% of all cases. The predominant cause of lung cancer is cigarette smoking, although environmental and occupational factors also can cause the cancer. Treatment options generally include systemic chemotherapy or protein kinase inhibitors. In the most advanced cases, only the symptoms of the disease can be managed; there is a clear need for innovative new medicines for the treatment of lung cancer.

"Progress in lung cancer will come first from early diagnosis with patients presenting promptly with symptoms and second, with new drugs that are well tolerated and improve on current therapies. Incremental steps can lead to a meaningful impact on patients and society, given the frequency and aggressiveness of lung cancer," says Dr. Mary O’Brien, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, UK. "The positive CHMP opinion for ABRAXANE in combination with carboplatin for the treatment of adult patients with NSCLC is a significant step toward bringing a new treatment option to patients in Europe. The clinical data show patients had a significant positive response rate to the treatment, combined with an established safety profile. The therapy has also shown a significant response benefit for a subset of patients with squamous cell lung cancer, where there have been limited treatment advances in recent years."

The positive CHMP opinion was based on the results of a multicenter, randomized, open-label study including 1,052 chemotherapy-naive patients with Stage IIIb/IV non-small cell lung cancer. The study compared ABRAXANE in combination with carboplatin versus solvent-based paclitaxel in combination with carboplatin as first-line treatment in patients with advanced non-small cell lung cancer. The primary efficacy endpoint, overall response rate, was significantly higher for patients in the ABRAXANE/carboplatin arm at 33%, compared with patients in the control arm, at 25%. The most common adverse reactions

(≥ 20%) of ABRAXANE in combination with carboplatin for NSCLC were anaemia, neutropenia, thrombocytopenia, peripheral neuropathy, nausea, and fatigue.

Tuomo Pätsi, President of Celgene in Europe, the Middle East and Africa (EMEA), said, "The positive CHMP opinion is the first opportunity for Celgene to play a role in helping patients with NSCLC have access to an important treatment option in Europe. The anticipated European Commission decision would be the third approved indication for ABRAXANE, underscoring the value of this medicine. We are committed to ensuring that patients who need ABRAXANE will gain access to it once approved by the European Commission."

The CHMP reviews applications for all 28 member states in the European Union (EU), as well as Norway, Liechtenstein and Iceland. The European Commission, which generally follows the recommendation of the CHMP, is expected to make its final decision within approximately two months. If approval is granted, detailed conditions for the use of this product will be described in the Summary of Product Characteristics (SmPC), which will be published in the revised European Public Assessment Report (EPAR).

ABRAXANE is not currently indicated for the treatment of metastatic NSCLC in the European Union.

On January 23, 2015 The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Jakavi (ruxolitinib) for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea (Press release Novartis, JAN 23, 2015, View Source [SID:1234501375]). If approved in the EU, ruxolitinib could provide the first targeted treatment option for these patients.

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PV is a chronic, incurable blood cancer associated with an overproduction of blood cells that can cause serious cardiovascular complications, such as stroke and heart attack[1]. In PV, patients with resistance to or intolerance of hydroxyurea are considered to have uncontrolled disease, which is typically defined as hematocrit levels greater than 45%, elevated white blood cell count and/or platelet count, and may be accompanied by debilitating symptoms and/or enlarged spleen[1],[3],[4]. Elevated white blood cell count and hematocrit are also associated with an increased risk of blood clots[5].

"This positive CHMP opinion is encouraging news for patients with polycythemia vera who need effective treatment options," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. "If approved, ruxolitinib will be the first-ever targeted therapy for polycythemia vera in the EU, a positive step forward for the rare blood cancer community in Europe and a major development in Novartis’ continued commitment to help patients with high unmet needs."

In the EU, the European Commission generally follows the recommendations of the CHMP and delivers its final decision within three months of the CHMP recommendation. The decision will be applicable to all 28 EU member states plus Iceland, Norway and Liechtenstein. Global regulatory applications for ruxolitinib in PV are currently ongoing, and further regulatory filings are under review by health authorities. Ruxolitinib, which is marketed in the US by Incyte Corporation as Jakafi, received approval in December 2014 from the US Food and Drug Administration (FDA) for the treatment of patients with PV who have had an inadequate response to or are intolerant of hydroxyurea.

The CHMP recommendation was based on results from the pivotal Phase III RESPONSE clinical trial demonstrating that a significantly greater proportion of patients achieved the composite primary endpoint of hematocrit control (volume percentage of red blood cells in whole blood) without use of phlebotomy (a procedure to remove blood from the body to reduce the concentration of red blood cells) and spleen size reduction when treated with ruxolitinib compared to best available therapy (21% compared to 1%, respectively; p<0.0001)[1],[2]. In addition, a greater proportion of patients in the ruxolitinib treatment arm achieved complete hematologic remission, as defined by the modified 2009 European LeukemiaNet (ELN) criteria, when compared to the standard therapy arm (24% compared to 9%, respectively; p=0.003)[2]. The data also showed more patients treated with ruxolitinib had a durable primary response at week 48 compared to patients treated with standard therapy (19% compared to 1%, respectively; (p<0.0001)[2].

Overall, ruxolitinib was well tolerated, and non-hematologic adverse events (AEs) were consistent with those previously seen in ruxolitinib studies in PV and myelofibrosis[2],[6],[7]. Within the first 32 weeks of treatment, the most common Grade 3 or 4 hematologic AEs in the ruxolitinib treatment arm were anemia (1.8%) and thrombocytopenia (5.5%)[2]. The most common non-hematologic AEs were dizziness (15.5%), constipation (8.2%) and herpes zoster (6.4%)[2]. The three most frequent non-hematological laboratory abnormalities (any Grade) were hypercholesterolemia (30.0%), raised alanine aminotransferase (22.7%) and raised aspartate aminotransferase (20.9%), which were mainly Grade 1 and 2[2].

On January 22, 2015 Advaxis reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application to conduct a Phase 1 clinical study of ADXS-HER2 (ADXS31-164) for the treatment of patients with metastatic HER2 expressing solid tumors (Press release Advaxis, JAN 22, 2015, View Source [SID:1234501367]). The clinical trial, which will be the first-in-human study of Advaxis’s lead Lm-LLO immunotherapy product for HER2 expressing cancers, is expected to begin patient enrollment in the first half of 2015. In May 2014, Advaxis was granted orphan drug designation by the FDA for ADXS-HER2 in osteosarcoma.

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The Phase 1 clinical study is designed to evaluate the safety and tolerability of ADXS-HER2 as a monotherapy in patients with metastatic HER2 expressing solid tumors such as breast, gastric, esophageal, and osteosarcoma. Results from the study will be used to determine the future clinical development program of ADXS-HER2.

"We are very pleased to have received FDA acceptance for our ADXS-HER2 IND application and look forward to commencing the Phase 1 clinical study in HER2 expressing solid tumors," stated Daniel J. O’Connor, President and Chief Executive Officer of Advaxis. "This trial will provide important insights about the potential of ADXS-HER2 in HER2 expressing cancers such as breast, gastric, esophageal and osteosarcoma."

The safety and efficacy of ADXS-HER2 is currently being evaluated in an ongoing Phase 1/2 veterinary clinical study in pet dogs with osteosarcoma, conducted by Nicola Mason, BVet.Med, Ph.D., DACVIM, of the University of Pennsylvania School of Veterinary Medicine. To date, dogs treated (n=15) with ADXS-HER2 immunotherapy, after receiving standard of care (amputation and follow up chemotherapy), had a statistically significant overall survival benefit (p=0.032) compared to dogs (n=13) that only received standard of care. Additionally, the preliminary data suggests immune responses induced by ADXS-HER2 targeted pulmonary micrometastases and prevent the development of metastatic disease in the dog’s lungs.

Advaxis has granted exclusive worldwide rights to Aratana Therapeutics (Nasdaq:PETX) to develop and commercialize ADXS-HER2 for the treatment of osteosarcoma in dogs. In July 2014, Aratana filed a U.S. Department of Agriculture (USDA) product license application for ADXS-HER2 for the treatment of canine osteosarcoma and other cancers. While the USDA has no specific obligation to respond within a prescribed timeframe, the companies expect a response within 12 to 18 months from the date the application was filed.