Novartis drug Jakavi® recommended by CHMP for EU approval to treat adults with rare blood cancer polycythemia vera

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].

Incyte Earns $25 Million Milestone as Jakavi® (ruxolitinib) Recommended for Approval in Europe for Polycythemia Vera

On January 23, 2015 Incyte reported that it has earned a $25 million milestone payment from Novartis (Press release Incyte, JAN 23, 2015, View Source [SID:1234501376]). This payment was triggered by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopting a positive opinion for Jakavi (ruxolitinib) for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea. Incyte expects to record this amount as contract revenue, and receive the $25 million payment, in the first quarter of 2015.

“We are very pleased with the progress that Novartis has made in the global development and commercialization of Jakavi,” stated Hervé Hoppenot, President and Chief Executive Officer of Incyte. “This recommendation for approval in Europe, the second indication for Jakavi and many months ahead of schedule, is further evidence that our innovative scientific advances can offer significant benefit to patients.”

Under the Incyte-Novartis Collaboration and License Agreement signed in 2009, Novartis received exclusive development and commercialization rights to ruxolitinib outside of the United States for all hematologic and oncologic indications, and sells ruxolitinib under the name Jakavi. Ruxolitinib is marketed by Incyte in the United States as Jakafi (ruxolitinib).

Array Announces Agreement To Acquire ENCORAFENIB (LGX818)

On January 23, 2015 Array BioPharma reported that it has reached a definitive agreement with Novartis Pharma AG to acquire worldwide rights to encorafenib (LGX818), a BRAF inhibitor currently in Phase 3 development (Press release Array BioPharma, JAN 23, 2015, View Source [SID:1234501374]). This agreement is conditional on the closing of transactions announced by Novartis and GlaxoSmithKline PLC (GSK) on April 22, 2014, which are expected to close in the first half of 2015, and the agreement remains subject to the receipt of regulatory approvals. Array previously announced a definitive agreement with Novartis to regain global rights to the Phase 3 MEK inhibitor binimetinib, the material terms of which remain in place following this agreement. In order to address competition concerns raised by the European Commission, Array has agreed to obtain an experienced partner for global development and European commercialization of both binimetinib and encorafenib. The European Commission is expected to issue a decision regarding the Novartis-GSK transaction on January 28, 2015.

“Acquiring worldwide rights to encorafenib, an innovative late-stage oncology product, represents a tremendous opportunity for Array,” said Ron Squarer, Chief Executive Officer, Array BioPharma. “There are currently eleven active encorafenib clinical trials, including the Phase 3 COLUMBUS trial in which encorafenib is being studied in combination with binimetinib for BRAF+ melanoma patients. With rights to both encorafenib and binimetinib, Array would enhance its position to broadly develop and commercialize each product, as well as this MEK/BRAF combination, which may have differentiating advantages when compared to available therapies.”

Terms of the Agreement

Upon satisfaction of all conditions and closing of the deal, Array will acquire global rights to encorafenib. Other than a de minimis payment due to Novartis from Array, there are no milestone payments or royalties payable under this agreement by either party. Novartis has agreed to provide transitional regulatory, clinical development and manufacturing services as specified below and will assign or license to Array all patent and other intellectual property rights Novartis owns to the extent relating to encorafenib. As part of the transaction, Array has agreed to obtain an experienced partner for global development and European commercialization of both binimetinib and encorafenib. If Array is unable to find a suitable partner in the prescribed time period, a trustee would have the right to sell such European rights.

Novartis will conduct and fund the COLUMBUS trial through the earlier of June 30, 2016 or completion of last patient first visit. At that time, Array will assume responsibility for the trial, while Novartis will reimburse Array for out-of-pocket costs along with 50% of Array’s full time equivalent (FTE) costs in connection with completing the COLUMBUS trial. Novartis is responsible for conducting all other encorafenib trials until their completion or transfer to Array for a defined transition period. For all trials transferred to Array, Novartis will reimburse Array for out-of-pocket costs and 50% of Array’s FTE costs in connection with completing the trials.

Novartis will supply encorafenib for clinical and commercial use for up to 30 months after closing and will also assist Array in the technology and manufacturing transfer of encorafenib. Novartis will also provide Array continued access to several Novartis pipeline compounds for use in currently ongoing combination studies, and possible future studies, including Phase 3 trials, with encorafenib. The effectiveness of the agreement is subject to the receipt of regulatory approvals and to the consummation of the Novartis-GSK transaction.

In addition, Array agreed to undertake to obtain certain third party consents or waivers necessary for Array to consummate the transactions under the Novartis Agreement.

Advaxis Announces FDA Acceptance of Its Investigational New Drug Application to Commence First-in-Human Clinical Trials of ADXS-HER2

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.

Syncona LLP and UCL Business PLC Announce the Formation of Autolus Limited, a Cancer Immunotherapy Company

On January 22, 2015 Syncona and UCL Business, the wholly-owned technology transfer company of University College London (“UCL”), reported the creation of Autolus Limited (“Autolus”), a biopharmaceutical company focused on the development and commercialisation of next-generation engineered T-cell therapies for haematological and solid tumours (Press release Autolus, JAN 22, 2015, View Source [SID:1234501365]). Autolus is founded upon the work of Dr Martin Pule, an academic clinical haematologist and thought-leader in T-cell engineering. Syncona has committed £30m to Autolus in a Series A financing. Dr Christian Itin, former CEO of Micromet and a leader in the cancer immunotherapy field, has joined the company as Chairman.

Recent clinical trials of engineered T-cell treatments for haematological malignancies performed by various groups suggest that chimeric antigen receptor (“CAR”) T-cells have the potential to transform cancer therapy. Realisation of that potential will require innovative technologies to program the properties of T-cells to increase efficacy and safety, and to access tumour types which are not addressable with the current generation of CAR T-cell technology. Autolus is a next-generation engineered T-cell company, developing a series of CAR T-cell products based on its proprietary targets, constructs and technologies.

Martin Pule, Chief Scientific Officer of Autolus and Senior Lecturer at the UCL Cancer Institute and NIHR University College London Hospitals Biomedical Research Centre, commented:
“It is exciting to be involved in Autolus, where we have an opportunity to bring innovative new therapeutic approaches to patients who often have no alternative treatment path. The key will be to remain at the cutting-edge of T-cell engineering to create a new generation of programmed T-cells acting as autonomous agents to kill tumour cells. What we’ve seen so far in the CAR T-cell field is only the beginning.”

Christian Itin, Chairman of Autolus, said:
“A key element of Autolus’ strategy is to progress CAR T-cell products quickly into clinical trials, leveraging our strong partnership with UCL. The company has engaged a team of thought-leading academics in London as advisors, and will perform its Phase 1 clinical studies and manufacturing within the academic infrastructure of the city, including the integrated cancer clinical trials infrastructure at University College Hospital and the expert cell therapy manufacturing facility at the UCL Institute of Child Health and Great Ormond Street Hospital.”

Edward Hodgkin, Partner with Syncona LLP and Chief Executive Officer of Autolus, added:
“Autolus is a great fit with Syncona’s strategy. We are focussed on building companies in areas of cutting-edge science with the potential to deliver extreme efficacy to patients. CAR T-cell products have the potential to transform cancer therapy, and we expect Autolus to be at the forefront of a revolution in medicine in which human cells are used to treat disease. We have a very talented team and are delighted to have attracted Christian Itin to act as Chairman of the Company.”

Cengiz Tarhan, Managing Director of UCLB, said:
“UCL is a world leader in the biomedical sciences, with an unremitting commitment to outstanding research and translation into healthcare benefits for patients. It is exciting to support these breakthrough treatments being taken forward in a commercial environment in a way that may benefit patients globally. The formation of Autolus represents the culmination of several years of research in the laboratories of Martin Pule and his collaborators drawing on funding from multiple government and charitable sources. UCLB are delighted to be able to partner with Syncona to launch Autolus.”