On October 10, 2014 ARIAD Pharmaceuticals reported that the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has concluded its review of Iclusig (ponatinib) under the Article 20 referral procedure and has recommended that Iclusig continue to be used in Europe in accordance with its already approved indications (Press release Ariad, OCT 10, 2014, View Source;p=RssLanding&cat=news&id=1976197 [SID:1234500818]).

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"We are grateful for the rigorous and in-depth review provided by the PRAC and the Scientific Advisory Group for Oncology," stated Harvey J. Berger, M.D., chairman and chief executive officer of ARIAD. "The PRAC recommendation provides insightful guidance to healthcare professionals and patients regarding the use of Iclusig in patients with Ph+ leukemias and importantly, leaves the original Iclusig indication statement unchanged. We look forward to consideration and adoption of these recommendations by the CHMP later this month and authorization by the European Commission by the end of the year."

The authorized indications of Iclusig in Europe, as approved in July 2013, are as follows:

The treatment of adult patients with chronic phase, accelerated phase or blast phase chronic myeloid leukaemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation, or
The treatment of adult patients with Philadelphia-chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation.

Other recommendations made by the PRAC related to the Iclusig Summary of Medicinal Product Characteristics (SmPC) include, (1) patient monitoring for response according to standard clinical guidelines, (2) consideration of Iclusig dose-reduction following achievement of major cytogenetic response with subsequent monitoring of response and, (3) consideration of Iclusig discontinuation if a complete haematologic response has not been achieved by three months. Further information is provided indicating that the risk of vascular occlusive events is likely dose-related. An update of the Warning and Precautions and Undesirable Effects sections is also provided for inclusion in the Iclusig SmPC.

"The recommendation from the PRAC confirms a positive benefit-risk assessment for Iclusig after thorough consideration of updated safety information," said Stephen G. O’Brien, M.D., Ph.D., Professor of Haematology at the Northern Institute for Cancer Research at Newcastle University, United Kingdom. "This is a good outcome for patients and healthcare professionals in Europe as it continues to offer a treatment option to CML patients who have become resistant to, or intolerant of, certain other TKIs."

The PRAC is the committee at the EMA that is responsible for assessing and monitoring safety issues for human medicines. The PRAC’s recommendations are considered by the CHMP when it adopts opinions for centrally authorized medicines and referral procedures.

On October 9, 2014 GenSpera reported that patient enrollment has been completed in the company’s Phase II clinical trial in patients with liver cancer (hepatocellular carcinoma) (Filing 8-K , GenSpera, OCT 10, 2014, View Source [SID:1234500819]). Formal results of the study are expected to be available during the first quarter of 2015.

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"We are grateful to the trial investigators for their efforts, as well as the patients and their loved ones who are supporting this important trial," said Craig Dionne, PhD, GenSpera’s CEO. "The completion of the enrollment period for this trial marks another company milestone. The data we have collected to date establish proof of concept for mipsagargin’s destruction of blood vessels within tumors and encouraging signs of potential anti-tumor activity. We anticipate similar results in our ongoing Phase II trials in patients with glioblastoma as well as our planned Phase II trial in patients with prostate cancer."

Interim data from the ongoing Phase II clinical trial in liver cancer patients were recently presented at the Asia Pacific Primary Liver Cancer Expert Meeting in Taipei in July 2014 (APPLE2014) and at the International Liver Cancer Association (ILCA) meeting in Kyoto in September 2014. Impressively, 80% of liver cancer patients in the Phase Ib and Phase II studies experienced disease stabilization at two months and a significant percentage of patients had stable disease for at least nine months after beginning treatment with mipsagargin.

The US Food and Drug Administration (FDA) granted Orphan Drug designation in 2013 for the evaluation of mipsagargin in patients with hepatocellular carcinoma.

On October 10, 2014 Ipsen reported positive results from the phase III study of triptorelin pamoate 11.25 mg (Decapeptyl 3 months) administered subcutaneously in patients with locally advanced or metastatic prostate cancer at the European Association of Urology (EAU) 14th Central European Meeting in Cracow, Poland (10-12 October 2014) (Press release Ipsen, OCT 10, 2014, View Source [SID:1234500820]).

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The primary objective of the study was to assess the efficacy and safety profile of the sustained-release triptorelin pamoate 11.25 mg (Decapeptyl 3 months) formulation when administered by the subcutaneous route in men with locally advanced or metastatic prostate cancer. This objective was met with castration levels of testosterone achieved in 97.6% [95% CI: 93.2-99.5] of men at week 4 and castration maintained in 96.6% of these men [95% CI: 91.6-99.1] at week 26.

Mean testosterone levels decreased to 18.4 ng/dl and 10.2 ng/dl at week 4 and week 8,
respectively, and remained within this range until the end of the study. Median time to achieve
castration was 22 days. For more than 90% of the patients, the level of testosterone was
maintained below 20 ng/dl from week 8 up to the end of the trial.

Median Prostate Specific Antigen (PSA) levels were reduced by 64.2% and 96.0% at week 4
and week 26, respectively. PSA levels remained within the normal range (0–4 ng/ml) from week 8 until the end of the study.

On October 10, 2014 Oxford BioMedica reported that it has signed further contracts with Novartis which build on the collaboration with Novartis announced in May 2013 (Press release Oxford BioMedica, OCT 10, 2014, View Source [SID:1234500821]).

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Under the terms of the new agreement, Novartis will pay $14 million upfront including a $4.3 million equity subscription for a non-exclusive worldwide development and commercialisation licence in oncology under the Group’s LentiVector platform. OXB will manufacture lentiviral vectors expressing CTL019/CART-019. The manufacturing contract has an initial three year term. Additionally, OXB has granted Novartis an exclusive licence for the worldwide development and commercialisation of all Chimeric Antigen Receptor (CAR) T cell products arising from the process development collaboration.

According to the terms of the deal, OXB is eligible to receive up to $90 million from Novartis over the next three years. This amount includes the upfront licence payment, the equity investment, manufacturing and process development services and various performance incentives. The equity investment comprises 70,807,500 ordinary shares at 3.8p, the average middle market price for the 10 business days prior to 7 October 2014. OXB will also receive undisclosed royalties on potential future sales of CTL019 and other CAR T cell products covered by the agreement.

Commenting on the announcement, John Dawson, Chief Executive Officer of Oxford BioMedica, said:

"We are delighted to sign a second agreement with Novartis. Oxford BioMedica now has a breadth of leading capabilities in gene and cell therapy under-pinned by a dominant LentiVector patent estate (licensed to multiple companies), and a state-of-the-art GMP manufacturing facility. Today’s commitment from Novartis, including their equity investment, strongly endorses this. Our team has demonstrated its ability to solve complex gene and cell therapy manufacturing challenges, and to develop the state-of-the-art analytics essential for such programmes.

"Oxford BioMedica aims to help facilitate access to life changing treatments for many more patients with a variety of clinical indications and is now strongly positioned to deliver significant value-creating results against its strong asset base."

On October 9, 2014 Takeda reported that the U.S. Food and Drug Administration (FDA) has approved VELCADE (bortezomib) for injection for use in previously untreated patients with mantle cell lymphoma (MCL) (Press release Takeda, OCT 9, 2014, View Source [SID:1234500832]). VELCADE is the first treatment in the United States to be approved for use in previously untreated patients with MCL. This approval extends the utility of VELCADE beyond relapsed or refractory mantle cell lymphoma, for which it has been approved since 2006.

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"Mantle cell lymphoma is a subtype of non-Hodgkin lymphoma that is usually a clinically aggressive malignancy, and it is a challenging disease to treat in part due to a relatively high risk of relapse," said Andrew Evens, DO, MSc, Director, Tufts Cancer Center; Chief, Division of Hematology/Oncology; Director, Lymphoma Program. "There are several new targeted drugs approved by the FDA for patients with relapsed or refractory disease, but up to this point, there had been none approved for the treatment of patients with previously untreated disease. VELCADE, when used in the VcR-CAP regimen, VELCADE, rituximab, cyclophosphamide, doxorubicin and prednisone, has demonstrated improved outcomes for patients, making it an important advance for the treatment of newly-diagnosed patients with mantle cell lymphoma."

This approval is based on the results of an international, randomized, head-to-head Phase 3 study that showed that previously untreated patients receiving a VELCADE-containing combination (VcR-CAP) experienced a 59 percent relative improvement in the study’s primary endpoint of progression-free survival (PFS) compared to those who were administered the standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) regimen (median 25 vs. 14 months; Hazard Ratio [HR] 0.63; P < 0.001) at a median follow up of 40 months. An Independent Review Committee (IRC) assessed the primary efficacy endpoint of PFS. The complete response (CR) rate for patients receiving VcR-CAP vs. R-CHOP was 44 percent vs. 34 percent.

"We are delighted VELCADE has received approval in previously untreated mantle cell lymphoma. The VELCADE-combination delivered an 11-month median advantage in progression-free survival as compared to a current standard of care," said Dixie-Lee Esseltine, MD, FRCPC, Vice President, Oncology Clinical Research, Takeda Pharmaceuticals International Co. "Since 2006, VELCADE has proven to be an important therapy for the treatment of relapsed or refractory mantle cell lymphoma, and it can now be used as an initial treatment for all patients with mantle cell lymphoma."

The open-label, multicenter, prospective study evaluated the efficacy and safety of VcR-CAP vs. R-CHOP in 487 patients with previously untreated MCL who were ineligible or not considered for a bone marrow transplant. VELCADE (1.3 mg/m2) is administered intravenously in combination with intravenous rituximab, cyclophosphamide, doxorubicin and oral prednisone (VcR-CAP) for six 3-week treatment cycles. VELCADE is administered first followed by rituximab. VELCADE is administered twice weekly for two weeks (days 1, 4, 8 and 11) followed by a 10‑day rest period on days 12‑21. For patients with a response first documented at cycle 6, two additional VcR-CAP cycles are recommended. At least 72 hours should elapse between consecutive doses of VELCADE.

The most common adverse reactions occurring in ≥20 percent of patients receiving the VcR-CAP regimen were neutropenia, leukopenia, anemia, thrombocytopenia, lymphopenia, peripheral neuropathy, pyrexia, nausea and diarrhea. Infections were reported for 31 percent of patients in the VcR-CAP arm and 23 percent of the patients in the R-CHOP arm including pneumonia (8 percent versus 5 percent). Adverse reactions leading to discontinuation occurred in 8 percent of patients in the VcR-CAP arm and 6 percent of patients in the R-CHOP arm. In the VcR-CAP group, the most commonly reported adverse reaction leading to discontinuation was peripheral sensory neuropathy (1 percent; 3 patients).