FDA approves Vistogard (uridine triacetate) for emergency treatment of chemotherapy overdose

The U.S. Food and Drug Administration today approved Vistogard (uridine triacetate) for the emergency treatment of adults and children  who receive an overdose of the cancer treatment fluorouracil or  capecitabine, or who develop certain severe or life-threatening 
toxicities within four days of receiving these cancer treatments.

 "Treating cancer requires not only selecting which drug may be most  effective and well tolerated, but ensuring the correct dose is given at  proper intervals. While rare, unintentional overdose can occur," said  Richard Pazdur, M.D., director of the Office of Hematology and Oncology  Products in the FDA's Center for Drug Evaluation and Research. "Today's  approval is a first-of-its-kind therapy that can potentially save lives following overdose or life-threatening toxicity from these chemotherapy agents."

 Fluorouracil (taken by infusion) and capecitabine (taken orally) are similar types of chemotherapy that have been used for decades to treat several types of cancer, including breast and gastrointestinal cancers. An overdose of fluorouracil or capecitabine is rare, but when it occurs,the effects are serious and can be fatal.

  

Vistogard, taken orally, blocks cell damage and cell death caused by fluorouracil chemotherapy. Patients should take Vistogard as soon as  possible after the overdose (whether or not they have symptoms) or early-onset (within four days) of severe or life-threatening toxicity. The patient's health care provider will determine when he or she should 
return to the prescribed chemotherapy after treatment with Vistogard.

  

The efficacy and safety of Vistogard were studied in 135 adult and pediatric cancer patients who were treated in two separate trials and had either received an overdose of flourouracil or capecitabine, or had early-onset, unusually severe or life-threatening toxicities within 96 
hours after receiving flourouracil (not due to an overdose). The studies' primary measure was survival at 30 days or until chemotherapy  could resume if prior to 30 days. Of those who were treated with  Vistogard for overdose, 97 percent were still alive at 30 days. Of those treated with Vistogard for early-onset severe or life-threatening toxicity, 89 percent were alive at 30 days. In both studies, 33 percent of patients resumed chemotherapy in less than 30 days.

FDA approves Vistogard (uridine triacetate) for emergency treatment of chemotherapy overdose

Role for carfilzomib in relapsed, refractory multiple myeloma treatment

In continuation of my update on carfilzomib

Carfilzomib significantly improves outcomes in previously treated patients with relapsed or refractory multiple myeloma, shows a head-to-head comparison with bortezomib.

In the ENDEAVOR phase III trial, published in The Lancet Oncology, median progression-free survival (PFS) was 18.7 months for the 464 patients randomly assigned to receive open-label carfilzomib plus dexamethasone. This was significantly longer than the 9.4 months for the 465 participants treated with bortezomib and dexamethasone, and equated to a 47% risk reduction in favour of carfilzomib.

Moreover, a significantly higher proportion of carfilzomib- than bortezomib-treated patients achieved an objective response, at 77% versus 63%, and the duration of response was also longer in the former group, at a respective 21.3 and 10.4 months.

The most common side effects of grade 3 or worse that occurred more frequently in the carfilzomib than the bortezomib treatment arm were anaemia and hypertension, with rates of 14% versus 10% and 9% versus 3%, respectively.

However, peripheral neuropathy of grade 3 was observed in 2% of carfilzomib-treated patients and there were no grade 4 events, compared with 8% of patients in the bortezomib arm who experienced events of grade 3 or 4.

Serious adverse events occurred in 48% of patients in the carfilzomib group and in 36% of those given bortezomib, but Meletios Dimopoulos (National and Kapodistrian University of Athens, Greece) and team note that the number of discontinuations and deaths attributable to adverse events were comparable between the groups.

They conclude that carfilzomib plus dexamethasone could be considered for multiple myeloma patients for whom bortezomib is indicated.

Role for carfilzomib in relapsed, refractory multiple myeloma treatment

Alecensa (alectinib) approved for treatment of people with advanced ALK-positive NSCLC

The U.S. Food and Drug Administration today approved Alecensa (alectinib) to treat people with advanced (metastatic) ALK-positive non-small cell lung cancer (NSCLC) whose disease has worsened after, or who could not tolerate treatment with, another therapy called Xalkori (crizotinib).

Lung cancer is the leading cause of cancer death in the United States, with an estimated 221,200 new diagnoses and 158,040 deaths in 2015, according to the National Cancer Institute. An ALK (anaplastic lymphoma kinase) gene mutation can occur in several different types of cancer cells, including lung cancer cells. ALK gene mutations are present in about 5 percent of patients with NSCLC. In metastatic cancer, the disease spreads to new parts of the body. In ALK-positive NSCLC metastatic patients, the brain is a common place for the disease to spread.

 Crizotinib

"Today's approval provides a new therapy for a group of patients who would have few treatment options once their disease no longer responds to treatment with Xalkori," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "In addition to the primary effect on tumors in the lung, Alecensa clinical trials provide evidence of an effect on tumors that had spread to the brain, which is an important effect for clinicians to understand."

Alecensa is an oral medication that blocks the activity of the ALK protein, which may prevent NSCLC cells from growing and spreading.

Alecensa (alectinib) approved for treatment of people with advanced ALK-positive NSCLC

Single dose of psilocybin decreases anxiety, depression in cancer patients

In continuation of my update on Psilocybin

A single dose of psilocybin, the major hallucinogenic component in magic mushrooms, induces long-lasting decreases in anxiety and depression in patients diagnosed with life-threatening cancer according to a new study presented today at the annual meeting of the American College of Neuropsychopharmacology.

Patients who receive a cancer diagnosis often develop debilitating symptoms of anxiety and depression. Reports from the 1960s and 1970s suggest that hallucinogenic drugs such as LSD may alleviate such symptoms in cancer patients, but the clinical value of hallucinogenic drugs for the treatment of mood disturbances in cancer patients remains unclear. In this new study, Roland Griffiths and colleagues from the Johns Hopkins University School of Medicine investigated the effects of psilocybin on symptoms of anxiety and depression in individuals diagnosed with life-threatening cancer. Five weeks after receiving a dose of psilocybin sufficiently high to induce changes in perception and mystical-type experiences, patients reported significantly lower levels of anxiety and depression compared with patients that received a low dose of the drug. The positive effects on mood persisted in the patients at 6 month follow-up.

The authors suggest that a single dose of psilocybin may be sufficient to produce enduring decreases in negative mood in patients with a life-threatening cancer.

Single dose of psilocybin decreases anxiety, depression in cancer patients

New heart failure drug may increase patients' risk of Alzheimer's disease, macular degeneration

In continuation of my update on sacubitril and Valsartan

Patients with mild heart failure stand to benefit from a new drug that can halt the progression of their disease and reduce their risk of cardiovascular-related death. But the drug -- a tablet that combines the agents valsartan and sacubitril, sold under the trade name Entresto by drugmaker Novartis -- may be too good to be true, according to Arthur M. Feldman, MD, PhD, Executive Dean of the Lewis Katz School of Medicine at Temple University (LKSOM), Chief Academic Officer of the Temple University Health System, and Laura H. Carnell Professor of Medicine at LKSOM.

In an article published online December 7th in the Journal of the American Medical Association, Dr. Feldman and colleagues at Thomas Jefferson University and the University of Florida warn that valsartan/sacubitril could theoretically increase patients' risk of Alzheimer's disease and macular degeneration, a blinding condition affecting the retina of the eye. The article raises these concerns about the drug, which was approved by the U.S. Food and Drug Administration in July 2015.

"Basic science data has caused us to speculate that off-target effects of valsartan/sacubitril may cause an exacerbation of Alzheimer's disease and could also exacerbate the course of macular degeneration," Dr. Feldman explained.

Dr. Feldman went on to note that "doctors are prescribing these drugs without knowledge of these theoretical risks."

Valsartan/sacubitril works by inhibiting an enzyme known as neprilysin, which normally plays a critical role in breaking down a wide array of peptides in cells. Among those substances are the so-called natriuretic peptides, which function in regulating scarring and cell growth in the heart when neprilysin is blocked. Because of those activities, valsartan/sacubitril can delay the progression of heart failure in some patients.

Neprilysin, however, also normally degrades amyloid beta, a peptide that can accumulate in the brain, where it contributes to Alzheimer's disease, as well as in the eye, where it is implicated in macular degeneration. The balance between the production and clearance of amyloid beta is crucial to the pathogenesis of Alzheimer's disease and is suspected to influence the development of macular degeneration. In animal models, blocking neprilysin disturbs that balance and exacerbates the development of Alzheimer's pathology.

New heart failure drug may increase patients' risk of Alzheimer's disease, macular degeneration

Marqibo now available to leukemia patients through myTomorrows' Internet-based platform

myTomorrows (Amsterdam, the Netherlands), announced today that it has started a collaboration with Spectrum Pharmaceuticals, Inc. (Henderson, USA; NasdaqGS: SPPI) to provide access to its liposome-encapsulated vincristine for treatment of Philadelphia chromosome negative acute lymphoblastic leukemia.

In August 2012, the US FDA approved the product for treatment of this rare type of leukemia. Through myTomorrows' Internet-based platform, the product is now also made available to patients and doctors in all other countries of the world, except China, Taiwan and Hong Kong, through an Early Access Program.

"We are pleased to make Marqibo® also available to leukemia patients outside of the United States, in countries where the treatment did not yet receive market approval," said Dr. Ronald Brus MD, founder and CEO of myTomorrows. "By taking care of the complex and time consuming process of receiving approval from regulatory authorities and healthcare insurers for individual patients, we aim to unburden these patients and their physicians by fulfilling their request as quickly as possible."

Joseph Turgeon, President and COO of Spectrum Pharmaceuticals said "We look forward to expand our collaboration with myTomorrows to also bring this product to doctors and patients through myTomorrows' global platform. It provides an additional option for acute lymphoblastic leukemia patients whose disease is unresponsive to available therapies and underscores Spectrum's efforts to combat this terrible disease."

Marqibo now available to leukemia patients through myTomorrows' Internet-based platform

Cancer drug can neutralize toxic RNA that causes myotonic dystrophy

A group of researchers has shown for the first time in cells and in a mouse model that a drug used to treat cancer can neutralize the toxic RNA that causes the prolonged muscle contractions and other symptoms of myotonic dystrophy type 1, the most common form of adult-onset muscular dystrophy. The researchers report their findings today Dec. 10, 2015 in the journal Cell Reports. (actinomycin-D)

"This finding opens a new avenue for a therapeutic strategy for this disease," said Andrew Berglund, Ph.D., a professor of biochemistry and molecular biology in the University of Florida College of Medicine. "This is the first evidence that specifically inhibiting transcription can be effective in knocking down the toxic material that causes the disease."

In myotonic dystrophy and other related neurological disorders, the symptoms stem from repeated individual nucleotides, or "building blocks," in the RNA in muscle tissue cells that can build up over time. These repeats, called CTG expansions in myotonic dystrophy type 1, become 'toxic' when transcribed from DNA. The expansions disrupt the RNA binding proteins responsible for splicing, the 'editing' needed so that the RNA can create appropriate proteins that allow muscles to function properly.

Cancer drug can neutralize toxic RNA that causes myotonic dystrophy

Tetra begins human Phase 1 safety trials of BPN14770

Tetra Discovery Partners ("Tetra") today announced that the company has initiated human Phase 1 safety trials of its lead compound BPN14770, which Tetra is developing as a potential treatment to both improve memory and slow the progression of Alzheimer's disease.

"There is a rapidly rising need for improved therapies for Alzheimer's disease. BPN14770 offers a novel approach that intervenes in important neural pathways related to learning and memory storage that underlie daily cognitive function in patients with Alzheimer's disease," said Mark Gurney, Ph.D., chairman and chief executive officer of Tetra. "Tetra Discovery has begun an initial human safety study with the compound in healthy volunteers, and expects to expand this to initial explorations of the compound benefit for cognition during 2016."

Tetra's Phase I clinical trials are designed to first evaluate BPN14770 in a single ascending dose study (SAD) to assess the safety, tolerability and pharmacokinetics in 48 healthy human volunteers. Endpoints for the study are safety, tolerability, and pharmacokinetics. Afterward, a multiple ascending dose (MAD) study will take place, enrolling young and elderly subjects to provide preliminary efficacy assessment of BPN14770 on long-term memory and other cognitive processes.

BPN14770 was developed through a cooperative research agreement with the National Institutes of Health (NIH) Blueprint Neurotherapeutics Network. "Tetra benefited greatly from the deep industry experience and commitment of NIH Blueprint consultants, CROs, and staff, the National Institute of Neurological Disorders & Stroke (NINDS) and the National Institute of Aging (NIA). The cooperative research program was milestone driven with a rigorous focus on meeting pharmaceutical industry metrics for CNS drug quality and safety. BPN14770 has shown efficacy in multiple animal models of learning and memory with an excellent safety margin for human clinical trials," commented Dr. Gurney.

Tetra begins human Phase 1 safety trials of BPN14770

New class of diabetes drugs differs in efficacy and safety profiles, shows new research

Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) differ in their efficacy and safety profiles, according to new research by the University of Leicester.

Compared to other once-weekly GLP-1RAs which are licensed and available, dulaglutide 1.5mg and once weekly exenatide showed the greatest reduction of HbA1c and fasting plasma glucose.

GLP-1RAs are a relatively new class of drugs that stimulate insulin and inhibit glucagon secretion, slow gastric emptying, and reduce food intake. While the first approved GLP-1RAs are administered as subcutaneous daily injections, more recently GLP-1RAs available via once-weekly administration have emerged, reducing the number of injections and side effects and potentially improving patient compliance.

In clinical studies, these drugs improve glucose control and reduce body weight, without an increased risk for hypoglycaemia. To date, however, no direct comparisons between once-weekly GLP-1RAs are available.

The research – carried out by the university’s Diabetes Research Centre, which is based at the Leicester Diabetes Centre – used an innovative method to evaluate the efficacy and adverse effects of once-weekly GLP-1RAs in adults with Type 2 diabetes.

Researcher Dr Francesco Zaccardi and colleagues conducted a network meta-analysis of randomised trials. In the absence of direct evidence, network meta-analysis is an increasingly used statistical methodology that allows the estimation of the comparative effectiveness of multiple treatments.

Dr Zaccardi concluded:

Compared to other available once-weekly GLP-1RAs, dulaglutide 1.5mg and once weekly exenatide showed a greater reduction of HbA1c and fasting plasma glucose. The risk of hypoglycaemia among once-weekly GLP-1RAs was comparable. Taspoglutide, one of the agents evaluated, has already been withdrawn from the market for high rates of nausea, and this has been confirmed in the meta-analysis.

New class of diabetes drugs differs in efficacy and safety profiles, shows new research

Palbociclib and paclitaxel combination shrinks tumors in patient with ER positive breast cancer

Combining the new breast cancer drug palbociclib with paclitaxel (Taxol) shrank tumors in nearly half of patient with estrogen-receptor (ER) positive breast cancer, according to new research from the Perelman School of Medicine at the University of Pennsylvania. The results will be presented Saturday at the 2015 San Antonio Breast Cancer Symposium (Abstract P6-13-08). A second study (Abstract P4-13-04), to be presented Friday provides new clues to how breast cancer develops resistance to the palbociclib, a common occurrence among many patients who take the drug.

"Results of the first study found that palbociclib and paclitaxel can be safely combined on an alternating dosing schedule," said Angela DeMichele, MD, MSCE, the Alan and Jill Miller Associate Professor in Breast Cancer Excellence in Penn's Abramson Cancer Center, and senior author on the study. "The high response rate we saw suggests this combination may hold benefits for patients over paclitaxel alone. Based on these results, a larger clinical trial to determine the benefits is warranted."

A Complementary Therapy

Palbociclib targets the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6, which help drive cell division and are upregulated in most cancers. The researchers suspected that palbociclib's unique mechanism of action may make it a good partner for other breast cancer drugs such as paclitaxel, which kills dividing cells at a certain point in the cell division process (also known as the "cell cycle"). Palbociclib effectively halts the cell cycle before that point, and thus in principle can synchronize cancer cells in a way that makes them more vulnerable to a closely following dose of paclitaxel.

Palbociclib and paclitaxel combination shrinks tumors in patient with ER positive breast cancer

New three-drug delivery system shows promise for treatment of metastatic melanoma

Researchers have developed a new three-drug delivery system for cancer treatment, especially metastatic melanoma, the deadliest form of skin cancer - and shown that the system may have particular value with cancers like this that often spread through the lymphatic system.

The new technology takes advantage of nanoparticles that can migrate to, and increase the effectiveness of an attack on cancer cells in the body's lymph nodes. This can also reduce the development of drug resistance and the broader toxicity often associated with this type of chemotherapy.

The findings were made with laboratory animals, and just published in the Journal of Controlled Release by researchers from the College of Pharmacy at Oregon State University. The work was supported by an OSU startup fund, and a provisional patent has been granted for this technology.

"Melanoma can be a very difficult cancer to treat because it often metastasizes and travels through the lymphatic system," said Adam Alani, an assistant professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, and lead author on this research.

"Melanoma has a high mortality rate because the lymph nodes tend to act as a haven for cancer cells, and allow them to resist treatment through chemotherapy," he said.

New three-drug delivery system shows promise for treatment of metastatic melanoma

Ibrutinib more effective than traditional chemotherapy in older untreated patients with CLL

In continuation of my update on ibrutinib

A multi-center, international, randomized, Phase III study of older untreated patients with chronic lymphocytic leukemia (CLL) demonstrated that ibrutinib, a kinase inhibitor, is significantly more effective than traditional chemotherapy with chlorambucil.

The study, which followed 269 patients, revealed a 24-month overall survival rate of 97.8 percent for patients taking ibrutinib versus 85.3 percent for those on chlorambucil. Minor adverse effects were reported.

Results from the study, led by Jan Burger, M.D., Ph.D. from The University of Texas MD Anderson Cancer Center, were published in today's online issue of the New England Journal of Medicine.

"Ibrutinib was superior to chlorambucil in CLL patients with no prior treatment, as measured by progression-free survival, overall survival, and response" said Burger, an associate professor in Leukemia. "The study also revealed significant improvements in hemoglobin and platelet levels."

Ibrutinib more effective than traditional chemotherapy in older untreated patients with CLL

XARELTO reduces rates of major bleeding, recurrent blood clots in people with deep vein thrombosis

In continuation of my update on rivaroxaban

Janssen Pharmaceuticals, Inc. (Janssen) and its development partner, Bayer HealthCare, today announced the results from their real-world study XALIA showing that, in people with deep vein thrombosis (DVT), the rates of major bleeding and recurrent blood clots for XARELTO® (rivaroxaban) in routine clinical practice were generally consistent with those observed in Phase 3 research. Patients taking XARELTO® also had shorter length of hospital stays than those given standard anticoagulation. The prospective study was presented at the 2015 American Society of Hematology (ASH) Annual Meeting and simultaneously published in Lancet Hematology.

"On average, every 37 seconds someone in the Western world dies from a venous blood clot, so it is important we understand the effectiveness and safety of available treatment options for these potentially life-threatening blood clots," said XALIA principal investigator Professor Alexander G. G. Turpie, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada. "The real-world insights from XALIA confirm the positive benefit-risk profile of rivaroxaban for the treatment of deep vein thrombosis that was observed in the Phase 3 EINSTEIN-DVT study, signalling that the medicine is performing as expected in patients that physicians typically see in everyday clinical practice."

XALIA – which included approximately 5,000 patients from 21 countries – evaluated the safety and effectiveness of XARELTO®, taken once daily, for the treatment of DVT in routine clinical practice as compared to standard anticoagulation. The primary outcome was the incidence of adverse events (major bleeding, recurrent blood clots and all-cause mortality). Healthcare resource utilization, including length of stay, also was evaluated. A propensity score analysis was completed to address differences in baseline characteristics and help correct any selection bias. Methodological and other differences between the studies limit the ability to directly compare results of XALIA to the pivotal Phase 3 EINSTEIN-DVT study, which was used by regulatory authorities worldwide to approve XARELTO®.

XARELTO reduces rates of major bleeding, recurrent blood clots in people with deep vein thrombosis

American scientists synthesize glycopolymers that prolong lifetime of healthy cells

Glycoproteins such as the mucins are assumed to be heavily involved in oncogenesis and metastasic spread. They are part of a strategy developed by malignant cells to resist or dodge the cell death machinery specialized for cells that show insufficient signaling through adhesions. Developing models for the mucins is very challenging, but American scientists have now synthesized glycopolymers that are not only recycled in the membrane, but also prolong the lifetime of healthy cells, as described in the journal Angewandte Chemie.

Glycosylated proteins like the mucins are regarded as responsible for promoting the survival mechanisms of malignant cells by segregating certain signaling proteins in the membrane. A major obstacle to studying this mechanism in detail has long been the lack of suitable model compounds that mimic the mucin functions. The group of Carolyn R. Bertozzi at Stanford University, CA, has now found a way to prepare such model compounds: They synthesize glycosylated polymers with lipid anchors that are readily inserted in the plasma membrane, but, thanks to further attachment of the polymer to a sterol compound, they are not degraded after ingestion in the cell, as the authors explain: "Cholesterylamine, a lipid known to recycle back to the cell surface after internalization, is capable of shuttling glycopolymers through this pathway continuously for up to ten days, resulting in the persistent display of glycopolymers on the plasma membrane." And, interestingly, the glycopolymers are not only persistent on the plasma membrane, they are also inherited in the dividing cells, as the authors say:

American scientists synthesize glycopolymers that prolong lifetime of healthy cells

Helsinn one step closer to bringing anamorelin HCI to market for treatment of anorexia, cachexia in NSCLC patients

Helsinn, the Swiss pharmaceutical Group focused on building quality cancer care, today announced that the European Medicines Agency (EMA) accepted for review, the marketing authorization application (MAA) for anamorelin HCI, a novel, orally active selective ghrelin receptor agonist under development for the treatment of anorexia, cachexia, or unintended weight loss in non-small cell lung cancer (NSCLC) patients.

Riccardo Braglia, Chief Executive Officer of Helsinn Group commented, "With this EMA submission, we are one step closer to bringing this new and potentially effective treatment to market, meaning that the quality of life for patients with non-small cell lung cancer who suffer from anorexia, cachexia, could soon improve. Anamorelin is part of our pipeline of products dedicated to cancer supportive care, all of which address areas of significant unmet medical need."

Helsinn one step closer to bringing anamorelin HCI to market for treatment of anorexia, cachexia in NSCLC patients