Encouraging results from cannabidiol trial for treatment-resistant epilepsy

Cannabidiol (CBD), a medical marijuana derivative, was effective in reducing seizure frequency and well-tolerated and safe for most children and young adults enrolled in a year-long study led by epilepsy specialists at NYU Langone Medical Center.

These latest findings provide the first estimates of safety, tolerability and efficacy of prescription CBD in children and adults with severe, highly treatment-resistant epilepsy. Led by Orrin Devinsky, MD, professor of neurology, neurosurgery, and psychiatry and director of the Comprehensive Epilepsy Center at NYU Langone, the study is published in the December 23 issue of Lancet Neurology. While early findings have been released at medical meetings -- including the 2015 American Academy of Neurology conference -- these are the first findings from the trial to be published in a peer-reviewed journal.

The study took place at 11 epilepsy centers across the country. Patients were given the oral CBD treatment Epidiolex over a 12-week treatment period. Results showed a median 36.5 percent reduction in monthly motor seizures, with the median monthly frequency of motor seizures falling from 30 motor seizures a month at the study's start to 15.8 over the 12 weeks. Equally important, CBD was shown to have a sufficient safety profile and was well-tolerated by many patients, despite some isolated adverse events.

"We are very encouraged by our trial results showing that CBD was safe and well-tolerated for most patients, and that seizures dropped significantly," says Devinsky. "But before we raise hopes for families who regularly deal with the devastation of treatment-resistant epilepsy, more research, including further studies through our ongoing randomized controlled trial, are needed to definitively recommend CBD as a treatment to patients with uncontrolled seizures."

Encouraging results from cannabidiol trial for treatment-resistant eplepsy

TIGER-X study reviews efficacy of rociletinib therapy in patients with EGFR mutant-positive NSCLC

Oncology & Hematology Review, the peer-reviewed journal, has published a review highlighting recent data around rociletinib, an investigational therapy in patients with previously treated EGFR mutant-positive non-small cell lung cancer.

Treatment for patients with non-small cell lung cancer (NSCLC) is being guided increasingly by driver mutations and, routinely, tumors from patients with adenocarcinoma are screened for mutations in the kinase domain of the epidermal growth factor receptor (EGFR) as well as for other genomic abnormalities (i.e. anaplastic lymphoma kinase [ALK] and ROS1 translocations). Effective, well-tolerated treatment options that specifically target the EGFR T790M mutation (the "gatekeeper" residue) in patients with NSCLC remains an unmet need. Rociletinib is an oral, irreversible, potent, covalent inhibitor of the activating EGFR mutations (del19 and L858R) and the T790M resistance mutation; it also spares wild-type EGFR. TIGER-X is the first of the TIGER trial series, which is a clinical development program for rociletinib in patients with mutant EGFR NSCLC. This phase I-II study is evaluating rociletinib in patients who have progressed following their first and only EGFR-directed tyrosine kinase inhibitor (TKI) therapy who have developed the T790M mutation and in later-line T790M positive patients who have progressed on their second or later TKI therapy or subsequent chemotherapy. In the ongoing TIGER-X study, rociletinib has shown encouraging activity in patients with EGFR mutant-positive NSCLC and is well tolerated. Future aims of the ongoing TIGER programme include to investigate rociletinib treatment in other lines of therapy, determine whether rociletinib treatment can lead to an improvement in overall survival (OS) and to explore the potential benefits of combining rociletinib with other anti-cancer agents such as anti-programmed cell death protein and programmed cell death 1 ligand 1 monoclonal antibodies, mitogen-activated protein kinase enzyme inhibitors, vascular endothelial growth factor inhibitors, and c-Met inhibitors. Other aims include evaluating the outcome of progression-free survival associated with rociletinib treatment and determining the efficacy of rociletinib in patients with T790M negative status.

TIGER-X study reviews efficacy of rociletinib therapy in patients with EGFR mutant-positive NSCLC

FDA approves Uptravi tablets to treat adults with pulmonary arterial hypertension

On December 21, the U.S. Food and Drug Administration approved Uptravi (selexipag) tablets to treat adults with pulmonary arterial hypertension (PAH), a chronic, progressive, and debilitating rare lung disease that can lead to death or the need for transplantation.

"Uptravi offers an additional treatment option for patients with pulmonary arterial hypertension," said Ellis Unger, M.D., director of the Office of Drug Evaluation I in the FDA's Center for Drug Evaluation and Research. "The FDA supports continued efforts to provide new treatment options for rare diseases."

PAH is high blood pressure that occurs in the arteries that connect the heart to the lungs. It causes the right side of the heart to work harder than normal, which can lead to limitations on exercise ability and shortness of breath, among other more serious complications.

Uptravi belongs to a class of drugs called oral IP prostacyclin receptor agonists. The drug acts by relaxing muscles in the walls of blood vessels to dilate (open) blood vessels and decrease the elevated pressure in the vessels supplying blood to the lungs.

Uptravi's safety and efficacy were established in a long-term clinical trial of 1,156 participants with PAH. Uptravi was shown to be effective in reducing hospitalization for PAH and reducing the risks of disease progression compared to placebo. Participants were exposed to Uptravi in this trial for a median duration of 1.4 years.

Common side effects observed in those treated with Uptravi in the trial include headache, diarrhea, jaw pain, nausea, muscle pain (myalgia), vomiting, pain in an extremity, and flushing.

FDA approves Uptravi tablets to treat adults with pulmonary arterial hypertension

Chi-Med announces initiation of Phase III sulfatinib registration trial in patients with NETs in China

Hutchison China MediTech Limited ("Chi-Med") (AIM: HCM) today announces that Hutchison MediPharma Limited ("HMP"), its drug R&D subsidiary, has initiated SANET-ep, a Phase III sulfatinib (HMPL-012) registration trial in China in patients with extra-pancreatic neuroendocrine tumors ("NETs"), which are all non-pancreatic NETs, including, for example, NETs originating in the lymph, lung and across the gastrointestinal tract. Preparations and site selection had begun in the middle of this year and the first patient was dosed on December 17, 2015.

SANET-ep is a randomized, double-blind, placebo-controlled, multi-center Phase III sulfatinib registration study to treat pathologically low or intermediate grade NET patients whose disease has progressed, locally advanced or distant metastasized and for whom there is no effective therapy. Patients will be randomized at a 2:1 ratio to receive either 300 milligrams of sulfatinib orally once per day, or placebo, on every 28-day treatment cycle. The primary objective of this study is to evaluate the progression-free survival of sulfatinib as compared to that of placebo, with secondary endpoints including objective response rate ("ORR"), disease control rate, time to response, duration of response, overall survival, safety and tolerability. Approximately 270 patients will be enrolled in the SANET-ep study from more than 20 centers across China, with top-line results expected in 2018.

Additionally, the second Phase III sulfatinib registration trial, SANET-p, in pancreatic NET patients, is expected to be initiated imminently in China. SANET-p employs a similar treatment regimen and has primary and secondary endpoints similar to those for SANET-ep trial. Approximately 195 patients will be enrolled in SANET-p and is expected to start by the end of 2015, with top-line results expected in 2017.

Chi-Med announces initiation of Phase III sulfatinib registration trial in patients with NETs in China

Zoledronate drug can protect stem cells from ageing

In continuation of my update on Zoledronic acid..

Stem cells can be protected from the effects of ageing by a drug currently used to treat patients with osteoporosis, a breakthrough study has found.

Scientists from the University of Sheffield discovered the drug zoledronate is able to extend the lifespan of mesenchymal stem cells by reducing DNA damage.

DNA damage is one of the most important mechanisms of ageing where stem cells lose their ability to maintain and repair the tissues in which they live and keep it working correctly.

The pioneering research shows the drug protects the stem cells from DNA damage enhancing their survival and maintaining their function.

Professor Ilaria Bellantuono, from the University's Department of Metabolism, said: "The drug enhances the repair of the damage in DNA occurring with age in stem cells in the bone. It is also likely to work in other stem cells too.

Zoledronate drug can protect stem cells from ageing

Novel drug candidate prevents nerve cell damage in mouse model of Parkinson's disease

A team of scientists at the University of Nebraska Medical Center (UNMC) and Longevity Biotech, Inc., has demonstrated that neuroprotection could be attained in preclinical models by a novel drug candidate that changes immune responses.

The results, published today in the Journal of Neuroscience, describe the prevention of nerve cell damage in a mouse model of Parkinson's disease. Notably, the drug protected nerve cells that produce dopamine, which is the chemical responsible for agility and movement that is lost in human disease.

"The results are exciting as they provide a bridge between the immune system and nerve cell protection in Parkinson's disease," said Scott Shandler, Ph.D., co-founder and CEO of Longevity Biotech.

"The idea was birthed nearly a decade ago when specific types of circulating blood cells called lymphocytes were found to damage the types of nerve cells responsible for disease," said Howard Gendelman, M.D., the Margaret R. Larson Professor and chair of the UNMC Department of Pharmacology and Experimental Neuroscience. "The new Longevity Biotech drug (LBT-3627) was able to change the function of these cells from killing the nerve cells to protecting them. This is especially significant for the Nebraska team, as the mechanism parallels closely the human trials nearing completion for Parkinson's patients."

LBT-3627 is similar to the naturally occurring vasoactive intestinal peptide (VIP), a well-established anti-inflammatory peptide with beneficial effects across a variety of disorders. VIP is rapidly degraded by the body and is unable to distinguish between its two naturally intended receptors (VPAC1 vs. VPAC2). These limitations have stymied prior translational success using VIP.

Novel drug candidate prevents nerve cell damage in mouse model of Parkinson's disease

Cancer drug may protect kidneys from damage caused by chemotherapy agent cisplatin

In continuation of my update on cis platin...

A class of drugs used increasingly to help fight cancer may have the additional benefit of protecting the kidneys when packaged with the powerful chemotherapy agent cisplatin.

The nearly 40-year-old cisplatin can be a strong opponent against aggressive cancers, such as head and neck, ovarian and lung cancers.

But in more than 10 percent of patients, the drug, given intravenously for typically a handful of days, can also take a quick and potentially deadly toll on the kidneys, said Dr. Ganesan Ramesh, kidney pathologist at the Vascular Biology Center at the Medical College of Georgia at Augusta University and at the university's Cancer Center.

Ramesh and his colleagues have new laboratory evidence that histone deacetylase inhibitors, or HDAC inhibitors, can eliminate 80-90 percent of that kidney toxicity.

"Cisplatin is a very effective drug, and we don't want to stop using it," said Ramesh, corresponding author of the study in the journal Kidney International. "We want to reduce its toxicity to the normal tissue."

The super-busy kidneys filter the entire blood volume of the body every 20 minutes. A big part of their job is removing toxins for elimination in the urine and pushing back into the body valuables such as glucose and nutrients. The major problem with cisplatin is it can get stuck in the kidneys, where the platinum metal compounds the drug releases to kill a tumor can do serious harm. Inside the kidneys, the malingerer stimulates inflammation, DNA damage, free-radical production and cell death.

When MCG researchers gave HDAC inhibitors to mice receiving cisplatin, it dramatically suppressed the usual inflammation and cell death that follow cisplatin dosing alone.

Histones are the protein spools DNA wraps around, and histone deacetylase enables DNA to be wound tightly and regulates gene expression and protein function. One way HDAC inhibitors help fight cancer is by temporarily loosening DNA, increasing the expression of tumor-suppressing genes and making the tumor more vulnerable. Evidence that HDAC inhibitors also can protect kidneys following injury, led Ramesh to reason it was logical to pair these drugs with cisplatin.

Cancer drug may protect kidneys from damage caused by chemotherapy agent cisplatin

Ibrutinib ‘new standard’ for relapsed, refractory mantle cell lymphoma

In continuation of my update on Ibrutinib and Temsirolimus

Temsirolimus

Phase III trial findings suggest that patients with relapsed or refractory mantle cell lymphoma derive significantly greater benefits from ibrutinib than from temsirolimus therapy.

Ibrutinib

The results of this direct comparison of the two treatment options approved in the European Union for this patient population “clearly establish ibrutinib as a new standard for treatment” of relapsed or refractory mantle cell lymphoma, says Peter Martin (Weill Cornell Medical College, New York, USA) in a comment accompanying the report in The Lancet.

He adds: “Many clinicians expect that, within the next 2 years, ibrutinib will find its way into the front-line setting for treatment of mantle cell lymphoma in combination with standard chemotherapy”.

In the trial, a total of 280 patients with relapsed or refractory disease who had previously been treated with at least one rituximab-containing regimen were followed up for a median of 20 months.

Median progression-free survival (PFS) was 14.6 months for the 139 patients randomly assigned to receive open-label oral ibrutinib and 6.2 months for the 141 patients given intravenous temsirolimus, a significant difference with a hazard ratio for progression or death of 0.43. The corresponding 2-year PFS rates were 41% and 7%.

Significantly more patients given the Bruton’s tyrosine kinase inhibitor ibrutinib achieved an overall response compared with those given the mammalian target of rapamycin antagonist temsirolimus, with rates of 72% versus 40%. And complete responses were observed in 19% and 1% of patients, respectively.

Ibrutinib ‘new standard’ for relapsed, refractory mantle cell lymphoma

Capecitabine increases disease-free survival for HER2-negative breast cancer patients

Treatment with the chemotherapy agent capecitabine increased disease-free survival for women with HER2-negative breast cancer that was not eliminated by presurgery chemotherapy, according to results from the phase III CREATE-X clinical trial presented at the 2015 San Antonio Breast Cancer Symposium, held Dec. 8-12.

Treatment given to shrink or eliminate a tumor before surgery is called neoadjuvant therapy. In some patients with breast cancer treated with neoadjuvant chemotherapy, residual invasive cancer can be detected in breast tissue samples and lymph nodes removed during surgery. These patients tend to have worse long-term outcomes compared with women who respond completely to neoadjuvant therapy.

"It has been suggested that patients with residual invasive disease after neoadjuvant chemotherapy have chemoresistant breast cancer, but there have been no large-scale clinical trials to test whether adjuvant systemic chemotherapy is beneficial for these patients," said Masakazu Toi, MD, PhD, a professor at Kyoto University Hospital in Japan, and founder and senior director of the Japan Breast Cancer Research Group (JBCRG). "CREATE-X was designed to evaluate this clinical question by testing whether capecitabine could improve disease-free survival for patients with residual invasive disease after neoadjuvant chemotherapy.

Capecitabine increases disease-free survival for HER2-negative breast cancer patients

Study reveals why anti-hormone therapy tamoxifen works better in some women than others

In continuation of my update on tamoxifen

The anti-hormone therapy tamoxifen can reduce breast cancer recurrence by about half in women with hormone-sensitive breast cancer. But it works better in some women than others. Researchers are not sure why.

"We do know that some tumors are inherently resistant to tamoxifen because of tumor genetic changes," says Daniel L. Hertz, Pharm.D., Ph.D., an assistant professor in the University of Michigan College of Pharmacy and member of the U-M Comprehensive Cancer Center.

"These tumor have found pathways to overcome anti-estrogen treatment. But we also believe some patients may be less likely to benefit from tamoxifen or endocrine therapy because of their genetics," Hertz says.

One theory is that in some patients, tamoxifen is not activated to the more potent estrogen inhibitor endoxifen. Patients with low levels of endoxifen may have worse outcomes on tamoxifen.

A meta-analysis by the International Tamoxifen Pharmacogenetics Consortium points to genetic variants. Researchers found patients with certain variants on the gene CYP2D6 had worse survival. Later analyses of prospective clinical trials, however, did not find the same link.

Study reveals why anti-hormone therapy tamoxifen works better in some women than others