2-year advanced melanoma survival benefit with dabrafenib, trametinib combination

Updated results from the COMBI-v trial show significantly improved overall and progression-free survival (OS, PFS) with first-line dabrafenib plus trametinib compared with vemurafenib in patients with advanced melanoma.

The findings of the phase III trial comprising patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma were presented at the European Cancer Congress in Vienna, Austria, by Caroline Robert, from the Institut Gustave Roussy in Paris, France.

A previous interim analysis with a median follow-up of 11 months showed a significant improvement in OS with dabrafenib and trametinib, explained Robert in her presentation, so much so that the trial was terminated early and patients in the vemurafenib group were allowed to crossover.

In this most recent analysis, the 352 patients randomly assigned to receive the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib had a median OS of 25.6 months. This was not only significantly longer than the 18.0 months observed for the 352 participants given the BRAF inhibitor vemurafenib, but also the “longest ever reached” in a randomised phase III trial in this patient population, said Robert.

And after a median follow-up of 19 months, the 2-year survival rate was significantly higher for the dabrafenib plus trametinib group than for the vemurafenib group, at 51% versus 38%.

Median PFS was also significantly longer, with corresponding times of 12.6 and 7.3 months, and overall response rate and duration of response were similarly improved in the dual therapy compared with the monotherapy arm, at 66% versus 53% and 13.8 versus 8.5 months, respectively.

The incidence of all-grade adverse events continued to be high during the additional follow-up period, with pyrexia (55%) most common in the combination group and arthralgia (52%) in the vemurafenib group, but Robert said this was not surprising.

2-year advanced melanoma survival benefit with dabrafenib, trametinib combination

Neurocrine Biosciences announces positive data from NBI-98854 Phase III trial in tardive dyskinesia

Neurocrine Biosciences, Inc. announced that NBI-98854, a highly selective small molecule VMAT2 inhibitor, showed a statistically significant reduction in tardive dyskinesia during the six weeks of placebo-controlled treatment in the Kinect 3 clinical trial. This Phase III trial included moderate to severe tardive dyskinesia patients with underlying schizophrenia, schizoaffective disorder, bipolar or major depressive disorder.

The pre-specified primary efficacy endpoint was the change-from-baseline in the Abnormal Involuntary Movement Scale (AIMS) at Week 6 in the 80mg once-daily dosing group compared to placebo as assessed by central blinded video raters. The AIMS ratings at Week 6 for the 80mg once-daily NBI-98854 intention-to-treat (ITT) population was reduced 3.1 points (Least-Squares Mean) more than placebo (p<0.0001).

"We are very pleased with the outstanding efficacy and side effect profile demonstrated by NBI-98854 in the Kinect 3 study. The efficacy data from this pivotal Phase III study completes our placebo-controlled dataset for NBI-98854 in tardive dyskinesia," said Kevin C. Gorman, President and Chief Executive Officer of Neurocrine. "We will now turn our focus to completing the open-label safety portion of the studies in tardive dyskinesia patients and compiling the data for both doses of NBI-98854 to be included in the New Drug Application we intend to file with the FDA in 2016."

"The results of this Kinect 3 study demonstrate the potential of NBI-98854 to be a safe and effective treatment for patients suffering from the debilitating effects of tardive dyskinesia and we look forward to sharing additional details of this important study at upcoming scientific meetings starting in mid-2016," said Christopher F. O'Brien, Chief Medical Officer of Neurocrine. "We want to thank the trial participants and investigators who contributed to this successful placebo-controlled portion of the Kinect 3 study and we look forward to continuing our work with them in the open-label safety assessment of NBI-98854 in patients suffering from tardive dyskinesia, as well as completing the initial Tourette syndrome study later this year."

Neurocrine Biosciences announces positive data from NBI-98854 Phase III trial in tardive dyskinesia

AcelRx Pharmaceuticals, Inc : Sufentanil

AcelRx Pharmaceuticals, Inc. (Nasdaq: ACRX), a specialty pharmaceutical company focused on the development and commercialization of innovative therapies for the treatment of acute pain, today provided a regulatory update on Zalviso™ (sufentanil sublingual tablet system) intended for the management of moderate-to-severe acute pain in adult patients in the hospital setting. The company has received formal minutes of the telephonic meeting held in early September 2015, with the Division of Anesthesia, Analgesia, and Addiction Products of the Food and Drug Administration (FDA). As reflected in the minutes, the Division restated at the meeting a request for clinical data to complement other data AcelRx has developed to assess the overall performance of the Zalviso device.

The company is planning to submit a protocol to the Division for a clinical study in post-operative patients designed to evaluate the effectiveness of changes made to enhance product performance. AcelRx expects to be ready to initiate the study in the first quarter of 2016, and likely will await comments on the protocol from the Division. The company will be prepared to work with the FDA to facilitate the timely study initiation.

"We have been preparing a clinical study to investigate the use of Zalviso in a more diverse post-surgical population than in our original Phase 3 studies," stated Pamela P. Palmer, MD, PhD, chief medical officer of AcelRx, "so we are modifying the design of this study to include endpoints that we believe will address the Division's concerns."

AcelRx Pharmaceuticals, Inc : Sufentanil

FDA grants Breakthrough Therapy Designation to Lilly's abemaciclib for treatment of metastatic breast cancer

Eli Lilly and Company (NYSE: LLY)   announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to abemaciclib, a cyclin-dependent kinase (CDK) 4 and 6 inhibitor, for patients with refractory hormone-receptor-positive (HR+) advanced or metastatic breast cancer. This designation is based on data from the breast cancer cohort expansion of the company's Phase I trial, JPBA, which studied the efficacy and safety of abemaciclib in women with advanced or metastatic breast cancer. Patients in this cohort had received a median of seven prior systemic treatments. These data were presented at the San Antonio Breast Cancer Symposium in 2014.

According to the FDA, Breakthrough Therapy Designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint.

FDA grants Breakthrough Therapy Designation to Lilly's abemaciclib for treatment of metastatic breast cancer

New drug may prevent malaria in pregnant women

Researchers at LSTM, working with colleagues of the Centres for Disease Control and Prevention (CDC) in Kenya and USA, and from the Kenya Medical Research Institution have found that a new drug may be more effective at preventing malaria in pregnant woman, especially where there is resistance to the current treatments.

LSTM's Professor Feiko ter Kuile, who heads the Malaria in Pregnancy (MiP) Consortium, was senior author on the study which has been published today in the journal The Lancet. The study evaluated the efficacy and safety of two alternative strategies in comparison to the standard treatment recommended for the prevention of malaria in 1546 HIV-negative pregnant women in western Kenya.

Malaria infection during pregnancy is a significant health problem to both the mother and the unborn child. It has been associated with chronic anaemia in the mother, and with loss of the pregnancy due to miscarriages or stillbirths and with low birth weight in pregnancies that result in livebirths, which in turn results in an increased risk of infant death. The World Health Organization (WHO) currently recommends that women in areas of stable malaria transmission receive intermittent preventative treatment in pregnancy (IPTp) with the antimalarial drug sulfadoxine-pyrimethamine (SP). Sulfadoxine-pyrimethamine is currently the only antimalarial drug that is recommended by WHO for this IPTp strategy, however high levels of resistance from the malaria parasite to this drug threatens its efficacy.

New drug may prevent malaria in pregnant women

Two studies identify promising new anti-retroviral strategy to combat HIV-1

A pair of studies by researchers at the University of Massachusetts Medical School, the University of Trento in Italy, and the University of Geneva in Switzerland, point to a promising new anti-retroviral strategy for combating HIV-1. The two studies, published online in Nature, show that the host cell membrane proteins SERINC5 and SERINC3 greatly reduce the virulence of HIV-1 by blocking the ability of the virus to infect new cells. HIV-1 encodes a protein called Nef that counteracts the SERINCs. New drugs that target the HIV-1 protein Nef would permit the SERINC proteins to inactivate the virus. The papers will appear in the October 8 issue of Nature.

"It's amazing, the magnitude of the effect that these proteins have on infectivity," said Jeremy Luban, MD, the David J. Freelander Professor in AIDS Research and professor of molecular medicine at UMass Medical School. "The SERINC proteins reduce the infectivity of HIV-1 virions by more than 100-fold."

Heinrich Gottlinger, professor of molecular, cell and cancer biology at UMass Medical School said, "The ability of HIV to inhibit these SERINC proteins has a profound impact on its capacity to infect other cells. Disrupting this mechanism could be a very powerful strategy for treating HIV and similar viruses that express the Nef protein."

The two studies, each done independently, used completely different, yet complementary, methodologies to unravel the complex interaction between the HIV-1 protein Nef and the cell surface membrane proteins SERINC5 and SERINC3, both of which are expressed in the immune system's T cells. Dr. Luban, working with former members of his lab, Massimo Pizzato, PhD, now of the University of Trento in Italy, and Federico Santoni of the University of Geneva in Switzerland, performed massively parallel sequencing on 31 human cell lines that differed in terms of the magnitude of dependence on Nef for HIV-1 replication. Independently, Dr. Gottlinger approached the problem biochemically. Conducting proteomic analysis of purified virions, he was able to identify host cell proteins that Nef regulated.

Two studies identify promising new anti-retroviral strategy to combat HIV-1

Two studies identify promising new anti-retroviral strategy to combat HIV-1

Experimental drug shows promise in mice with multiple sclerosis

An experimental drug originally identified in a National Cancer Institute library of chemical compounds as a potential therapy for brain and basal cell cancers improves the symptoms of mice with a form of the debilitating neurological disorder multiple sclerosis (MS), according to new research from NYU Langone Medical Center.

The experimental drug employed by the NYU Langone team of neuroscientists is called GANT61. It blocks the action of a key protein, Gli1, which is involved in so-called sonic hedgehog signaling, a biological pathway closely tied to neural stem cell development and the growth of some cancers, and whose signaling is raised in tissue samples taken from brain lesions in patients with MS.

A report describing the findings is being published in the journal Nature online Sept. 30.

In the study, mice with chemically damaged brain myelin were given daily doses of GANT61 for one month. Results showed that mice that received the drug had 50 percent more myelin at the end of treatment than did untreated mice. Myelin is the nerve-protecting sheath whose degradation is a principal cause of MS.

Experimental drug shows promise in mice with multiple sclerosis

Tris Pharma announces launch of generic TUSSIONEX

Tris Pharma, a specialty pharmaceutical company that develops innovative drug delivery technologies, announced the launch of Tris-labeled generic TUSSIONEX®, an extended-release suspension containing hydrocodone polistirex and chlorpheniramine polistirex.

Tussionex®, originally approved in the early 1980's, had no generic competition until 2010 when Tris Pharma's generic product entered the market under an exclusive distribution agreement with Par Pharmaceuticals. Under the terms of the distribution agreement, Par had the exclusive right to market Tris Pharma's hydrocodone polistirex and chlorpheniramine polistirex ER oral suspension for a five year period ending September 30, 2015. With the conclusion of the five year term, the rights have reverted back to Tris and as of October 1, 2015, hydrocodone polistirex and chlorpheniramine polistirex ER Suspension in 115ml and 473 ml bottles (compare to Tussionex®) will be marketed and distributed by Tris Pharma's generic business.

Tris Pharma announces launch of generic TUSSIONEX

Beta-catenin shows treatment target potential for TKI-resistant CML

Nuclear β-catenin could be a treatment target for patients whose chronic myeloid leukaemia (CML) is resistant to tyrosine kinase inhibitors (TKIs) independent of additional BCR–BL1 mutations, US researchers suggest.

“Collectively, our data implicate nuclear β-catenin in intrinsic BCR-ABL1 kinase-independent TKI resistance, but argue against a direct role for β-catenin in BM [bone marrow]-mediated (extrinsic) TKI resistance”, write Michael Deininger, from the University of Utah in Salt Lake City, and co-investigators.

However, writing in Leukemia, they add “the caveat that even primary CML cells cultured ex vivo on primary MSCs [mesenchymal stromal cells] may not fully recapitulate persistent leukemia cells in patients on long-term imatinib therapy, including heterogeneity across patients.”

The team demonstrated that imatinib therapy reduced β-catenin levels in TKI-sensitive cell lines but had no impact on β-catenin in cells lines with either intrinsic or extrinsic BCR-ABL1 kinase-independent TKI resistance, indicating that “imatinib-resistant cells have uncoupled β-catenin expression from BCR-ABL1 activity.”

Beta-catenin shows treatment target potential for TKI-resistant CML

AbbVie reports positive results from ABT-494 Phase 2 clinical trials in patients with rheumatoid arthritis

AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced results from two Phase 2 clinical trials evaluating its investigational selective JAK1 inhibitor, ABT-494, in patients with inadequate response to either methotrexate or TNF inhibitors. The clinical trials, BALANCE-I and BALANCE-II, achieved ACR20 at week 12 across all dose levels, except the lowest dose in BALANCE-II. BALANCE-I and BALANCE-II evaluated patients with moderate to severe rheumatoid arthritis with inadequate responses to prior anti-TNF (TNF-IR) or methotrexate (MTX-IR) treatment, respectively.

"We believe ABT-494 has the potential to become a best-in-class therapy, particularly in the most challenging patient population of TNF-inadequate responders," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "We are encouraged by the results of our Phase 2 studies and we will advance ABT-494 to Phase 3 studies with a once-daily formulation."

AbbVie reports positive results from ABT-494 Phase 2 clinical trials in patients with rheumatoid arthritis

Novo Nordisk announces FDA approval of Tresiba (insulin degludec injection) for diabetes treatment

Novo Nordisk, a world leader in diabetes care, today announced that the U.S. Food and Drug Administration (FDA) approved the new drug application for Tresiba® (insulin degludec injection), a once-daily, long-acting basal insulin. Tresiba® is indicated for use alone, or in combination with oral antidiabetic medicines or bolus insulin, and is approved for glycemic control in adults with type 1 and type 2 diabetes. Tresiba® provides a long duration of action beyond 42 hours. While patients are encouraged to take their insulin at the same time each day, Tresiba® allows patients to dose at any time of the day.

"Since 1923, Novo Nordisk has been committed to advancing insulin therapy for patients with diabetes, and we are proud to bring forward the first new basal insulin molecule to be approved by the FDA in 10 years," said Jesper Høiland, president of Novo Nordisk in the U.S. and executive vice president of Novo Nordisk A/S. "Novo Nordisk is excited to launch Tresiba® in the United States in the first quarter of 2016."

Ref : http://www.diapedia.org/management/insulin-degludec 

Novo Nordisk announces FDA approval of Tresiba (insulin degludec injection) for diabetes treatment

Allergan releases generic INVEGA (paliperidone extended-release tablets) in the U.S.

In continuation oof my update on paliperidone

Allergan plc (NYSE: AGN), a leading global pharmaceutical company, today announced that it has launched a generic version of Janssen's INVEGA® (paliperidone extended-release tablets) in the U.S. Allergan is the first company to receive FDA approval for and launch a generic version of INVEGA®, demonstrating the deep expertise of the Company's global generics R&D, regulatory and supply chain teams.

"This launch reinforces Allergan's commitment to developing, manufacturing and bringing to market high-quality, affordable versions of challenging products like INVEGA®, benefiting patients and reducing healthcare costs," said Robert Stewart, Allergan's Executive Vice President & President, Generics and Global Operations.

INVEGA® extended-release tablets are indicated for the treatment of schizophrenia in adults and adolescents (12-17 years of age).

For the 12 months ended July 31, 2015, INVEGA® had total U.S. brand sales of approximately $612 million, according to IMS Health data.

Allergan releases generic INVEGA (paliperidone extended-release tablets) in the U.S.

TUM scientists develop molecules that could pave way for new treatments to fight Alzheimer's, diabetes

When proteins change their structure and clump together, formation of amyloid fibrils and plaques may occur. Such 'misfolding' and 'protein aggregation' processes damage cells and cause diseases such as Alzheimer's and type 2 diabetes. A team of scientists from the Technical University of Munich (TUM) headed by Professor Aphrodite Kapurniotu have now developed molecules that suppress protein aggregation and could pave the way for new treatments to combat Alzheimer's, type 2 diabetes and other cell-degenerative diseases.

The scientists designed and studied 16 different peptide molecules in order to find out which of them are able to impede the 'clumping' of the proteins amyloid beta (Aß) and islet amyloid polypeptide (IAPP), which are associated with Alzheimer's and type 2 diabetes.

The molecules were designed on the basis of scientific work that shows that the Aß and IAPP proteins interact with each other, and that this 'cross-amyloid interaction' suppresses their clumping. The researchers selected short sequences of the IAPP protein that correspond to the key regions involved in the interaction with the Alzheimer's protein. These "hot segments" were then chemically linked to each other by using specific peptide segments as 'linkers' in order to mimic and optimize the IAPP cross-amyloid interaction surface.

Ref : http://www.tum.de/en/about-tum/news/press-releases/short/article/32611/

TUM scientists develop molecules that could pave way for new treatments to fight Alzheimer's, diabetes

SMC approves Bayer's Xofigo for treatment of castration-resistant prostate cancer in NHS Scotland

The Scottish Medicines Consortium (SMC) has today announced that Xofigo® (radium-223 dichloride) has been accepted for use within NHS Scotland for the treatment of adult patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no known visceral metastases.

While the National Institute for Health and Care Excellence (NICE) has published draft guidance recommending radium-223 dichloride in advanced prostate cancer, this does not cover all patients and may not be confirmed for a number of months and could change. In Scotland, under SMC guidance clinicians will have the choice to use Xofigo prior to chemotherapy or after. So while patient access has improved in Scotland, it is worsening in the rest of the UK.

“This is a positive step for advanced prostate cancer patients in Scotland. However, the picture in England, Wales and Northern Ireland is very different. Historically radium-223 dichloride has been available only in England, funded through the Cancer Drugs Fund (CDF). This CDF funding is due to cease later this year following the recent CDF delisting round,” said Mr Hugh Gunn, Tackle Prostate Cancer. “If NICE pass radium-223 dichloride for use, this will be for post chemotherapy patients only. This will prevent the use of radium-223 dichloride in men who, for one reason or another do not progress to chemotherapy.”

SMC approves Bayer's Xofigo for treatment of castration-resistant prostate cancer in NHS Scotland

Patients with advanced kidney cancer benefit from cabozantinib treatment

In continuation of my update on cabozantinib

Patients with advanced kidney cancer live for nearly twice as long without their disease progressing if they are treated with cabozantinib, a drug that inhibits the action of tyrosine kinases - enzymes that function as an "on" or "off" switch in many cellular processes, including cancer.

In the second of two late-breaking presentations of research that is predicted to change the way kidney cancer patients are treated, Professor Toni Choueiri will tell the presidential session of the 2015 European Cancer Congress, about results from the first 375 patients out of a total of 658 patients recruited to the phase III clinical METEOR trial comparing cabozantinib with everolimus, the current standard treatment for the disease.

Analysis of results in July 2015 showed that the estimated median (average) progression-free survival time for patients with advanced clear cell kidney cancer, randomised to receive cabozantinib, was 7.4 months, while it was 3.8 months for those receiving everolimus. The objective response rate (the proportion of patients whose tumours shrank, assessed up to 17 months) was 21% for cabozantinib and 5% for everolimus.

An interim analysis of overall survival among all of the 658 patients found that it was a third better for patients receiving cabozantinib. The findings are published simultaneously with the ECC2015 presentation in the New England Journal of Medicine.

Prof Choueiri, who is Associate Professor of Medicine at Harvard Medical School and Clinical Director and Kidney Cancer Center Director at The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, USA, said: "I am very excited about the outcome of the study since the results may change the standard of care in patients with advanced kidney cancer who have received prior standard therapy that targets the vascular endothelial growth factor receptor (VEGFR).

"Although treatment with VEGFR-targeted drugs has been very effective in the first line of therapy for patients with advanced kidney cancer, in many cases tumour cells find ways to escape control by these drugs. Cabozantinib is a new drug that targets possible escape mechanisms of tumour cells, including the tyrosine kinases MET, VEGFR and AXL. The results of the METEOR trial indicate that cabozantinib is able to shrink tumours and slow down tumour growth much better than current standard treatment in patients who previously received VEGFR-targeted drugs. This has resulted in a significant reduction in the rate of disease progression or death in the cabozantinib arm as compared with the everolimus arm. Regaining tumour control after prior targeted therapy may reduce symptoms related to kidney cancer and eventually help patients live longer.

Patients with advanced kidney cancer benefit from cabozantinib treatment