FDA Approves Ibrance (palbociclib) for Postmenopausal Women with Advanced Breast Cancer

In continuation of my update on palbociclib

The U.S. Food and Drug Administration today granted accelerated approval to Ibrance (palbociclib) to treat advanced (metastatic) breast cancer.

Breast cancer in women is the second most common type of cancer in the United States. It forms in the breast tissue and in advanced cases, spreads to surrounding normal tissue. The National Cancer Institute estimates that 232,670 American women were diagnosed with breast cancer and 40,000 died from the disease in 2014.

Ibrance works by inhibiting molecules, known as cyclin-dependent kinases (CDKs) 4 and 6, involved in promoting the growth of cancer cells. Ibrance is intended for postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have not yet received an endocrine-based therapy. It is to be used in combination with letrozole, another FDA-approved product used to treat certain kinds of breast cancer in postmenopausal women.

FDA Approves Ibrance (palbociclib) for Postmenopausal Women with Advanced Breast Cancer

FDA Approves Dutrebis (lamivudine and raltegravir) for HIV-1 Infection

   

The United States Food and Drug Administration (FDA) has approved Dutrebis, a fixed dose combination tablet containing 150 mg of lamivudine and 300 mg of raltegravir. Dutrebis tablet is approved for use in combination with other antiretroviral products for the treatment of HIV-1 infection in adults and pediatric patients greater than or equal to 6 years of age weighing at least 30 kg. The recommended dosage of Dutrebis is one tablet taken twice daily with or without food.

Dutrebis approval was based on an open-label, single dose, randomized, two-period, crossover study in healthy subjects (n=108). One Dutrebis fixed dose combination table was shown to provide comparable lamivudine and raltegravir exposures to one Epivir 150 mg tablet plus on Isentress 400 mg tablet. Due to the higher bioavailability of raltegravir contained in Dutrebis, the exposures provided by the 300 mg dose of raltegravir are comparable to 400 mg of ralegravir given as the raltegravir poloxamer formulation (Isentress), which accounts for the difference in raltegravir dose.

FDA Approves Dutrebis (lamivudine and raltegravir) for HIV-1 Infection

FDA Approves Lenvima (lenvatinib) for Differentiated Thyroid Cancer

LENVIMA, a kinase inhibitor, is the mesylate salt of lenvatinib. Its chemical name is 4- [3chloro-4-(N’-cyclopropylureido)phenoxy]-7-methoxyquinoline-6-carbox- amide methanesulfonate. The molecular formula is C₂₁H₁₉ClN₄O₄•CH₄O₃S, and the molecular weight of the mesylate salt is 522.96. The chemical structure of lenvatinib mesylate is:

The U.S. Food and Drug Administration today granted approval to Lenvima(lenvatinib) to treat patients with progressive, differentiated thyroid cancer (DTC) whose disease progressed despite receiving radioactive iodine therapy (radioactive iodine refractory disease).

FDA Approves Lenvima (lenvatinib) for Differentiated Thyroid Cancer

Maple syrup makes disease-causing bacteria more susceptible to antibiotics, study shows

A concentrated extract of maple syrup makes disease-causing bacteria more susceptible to antibiotics, according to laboratory experiments by researchers at McGill University.

The findings, which will be published in the journal Applied and Environmental Microbiology, suggest that combining maple syrup extract with common antibiotics could increase the microbes' susceptibility, leading to lower antibiotic usage. Overuse of antibiotics fuels the emergence of drug-resistant bacteria, which has become a major public-health concern worldwide. Prof. Nathalie Tufenkji's research team in McGill's Department of Chemical Engineering prepared a concentrated extract of maple syrup that consists mainly of phenolic compounds. Maple syrup, made by concentrating the sap from North American maple trees, is a rich source of phenolic compounds.

Maple syrup makes disease-causing bacteria more susceptible to antibiotics, study shows 

Newly approved drug for rare blood cancer shows sustained benefit for 2 years

In continuation of my update on Ibrutinib

 

We know that, Ibrutinib   also known as PCI-32765 and marketed under the name Imbruvica) is an anticancer drug targeting B-cell malignancies. It was approved by the US FDA in November 2013 for the treatment of mantle cell lymphoma and in February 2014 for the treatment of chronic  lymphocytic leukemia  It is an orally-administered, selective and covalent inhibitor of the enzyme Bruton's tyrosine kinase (BTK)  Ibrutinib is currently under development by Pharmacyclics, Inc and Johnson & Johnson'sJanssen Pharmaceutical division for additional B-cell malignancies including diffuse large B-cell lymphoma and multiple myeloma

--------------------

Now.....

The most recent results from a clinical trial show that ibrutinib, a newly approved drug for Waldenstrom's Macroglobulinemia, continued to control the rare blood cancer, with 95 percent of patients surviving for two years, report investigators from Dana-Farber Cancer Institute.

The median overall response rate was 91 percent after a median of 19 months of treatment, and in 69 percent of patients the cancer had not worsened two years after beginning treatment. When the cancer did progress, it began at a median time of 9.6 months after the start of treatment. The results are reported in The New England Journal of Medicine.

An earlier analysis of data from this phase 2 multicenter study supported the Food and Drug Administration's approval in January of ibrutinib as the first and only treatment for Waldenstrom's, a rare form of lymphoma that affects about 1,500 people annually in the United States.

"These findings herald a new era for the treatment of Waldenstrom's Macroglobulinemia, and show how genome sequencing can lead to the discovery of cancer mutations that can be specifically targeted by new therapies," said first author Steven Treon, MD, PhD, director of the Bing Center for Waldenstrom's Macroglobulinemia at Dana-Farber.

Newly approved drug for rare blood cancer shows sustained benefit for 2 years

New herbal tea to treat malaria in Africa

Malaria is a critical health problem in West Africa, where traditional medicine is commonly used alongside modern healthcare practices. An herbal remedy derived from the roots of a weed, which was traditionally used to alleviate malarial symptoms, was combined with leaves and aerial portions from two other plants with antimalarial activity, formulated as a tea, and eventually licensed and sold as an antimalarial phytomedicine. The fascinating story and challenges behind the development of this plant-based treatment are presented in The Journal of Alternative and Complementary Medicine, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on The Journal of Alternative and Complementary Medicinewebsite until May 14, 2015.

Dr. Merlin Willcox (University of Oxford, U.K.), Dr. Zéphirin Dakuyo (Phytofla, Banfora, Burkina Faso), and coauthors discuss the antimalarial and pharmacological properties of the herbal medication derived from Cochlospermum planchonii 

(a shrubby weed known as N'Dribala), Phyllanthus amarus,  

and Cassia alata. 

The authors provide a unique historical perspective in describing the early evaluation, development, and production of this phytomedicine. They present the ongoing research and challenges in scaling up cultivation and harvesting of the plants and in production of the final product. The article also describes other traditional uses of the medication, such as to treat hepatitis.

Ref : http://online.liebertpub.com/doi/full/10.1089/acm.2014.0147

New herbal tea to treat malaria in Africa

Itraconazole drug shows potential in cancer treatment

In continuation of my update on Itraconazole

Anti-fungal drug shows promise as potential new cancer treatment.A common anti-fungal treatment has joined the ranks of drugs that may be suitable for use in treating cancer, according to research from the Repurposing Drugs in Oncology (ReDO) project published in ecancermedicalscience.  

The ReDO project is an international collaboration of anticancer researchers dedicated to promoting the cause of common medicines which may represent an untapped source of novel therapies for cancer.

In partnership with ecancer, the ReDO project is publishing a series of papers on drugs that have enough clinical evidence to be taken to clinical trials.Itraconazole is a drug used to treat a broad range of fungal infections, including skin and nail infections.

It also has a lot of potential as a new cancer treatment, according to the ReDo project.

"Itraconazole shows potential in a number of areas with high unmet patient needs, particularly in non-small cell lung cancer and possibly in some rarer malignancies," says Pan Pantziarka, PhD, member of the ReDO project and the Anticancer Fund.

Itraconazole drug shows potential in cancer treatment

Effimune obtains regulatory approval for Phase I clinical trial in humans of its new immunomodulator FR104

Effimune announced today that it had received the authorization from the Belgian regulatory authority, the FAMHP (Federal Agency for Medicines and Health Products) for a Phase I clinical trial of FR104, its drug candidate for controlling the regulation of the immune system.

This double-blind randomized clinical trial will take place on 70 healthy volunteers (both men and women) over a period of 9 months, and will prepare the future development of FR104 in rheumatoid arthritis and kidney transplantation. The primary objectives of the trial are to establish the safety and tolerability of FR104 and assess its pharmacodynamics and pharmacokinetics. Since September 2013, FR104 has been under a global license agreement with Janssen Biotech, Inc., a subsidiary of Johnson & Johnson.

Benzoic acid, 2,3,4,5-tetrachloro-6-(2, 4,5,7-tetrabromo-6-hydroxy-3-oxo-3H-xanthen-9-yl) -

Effimune obtains regulatory approval for Phase I clinical trial in humans of its new immunomodulator FR104

Wilson Therapeutics' WTX101-201 Phase 2 clinical study to be presented at EASL annual meeting

Bis-choline tetrathiomolybdate, or WTX101, is a salt of tetrathiomolybdate (TTM, MoS₄²⁻) and choline currently under investigation as a therapy against Wilson's disease, a rare and potentially fatal disease in which the body cannot regulate copper. Wilson disease is an autosomal recessive genetic disorder that is manifested by serious hepatic, neurologic or psychiatric symptoms. The disease is fatal if left undiagnosed and untreated. It is estimated that approximately 1 individual in every 15,000 worldwide have Wilson's disease, corresponding to approximately 30,000 individuals in the European Union and approximately 20,000 in the United States.

Bionomics to present BNC105 trial results of metastatic renal cancer at Asian Oncology Summit

The data identify ferritin and IL-8 as two baseline biomarkers that correlate with an improved progression free survival (PFS) in patients. Eighty nine percent of patients expressing higher plasma levels of ferritin and lower plasma levels of IL-8 at baseline were disease progression-free at six months. The data show that biomarker-based patient selection has the potential to optimise clinical outcomes in the treatment of renal cancer. There are 6.3 new cases of renal cancer and 1.7 deaths per 100,000 people in Asia each year.

BNC105 is a novel compound being developed as a vascular disrupting agent (VDA) for the treatment of cancer. VDAs are drugs that disrupt the blood vessels that nourish tumours. This approach has a number of advantages over classical chemotherapy, including stronger impact on tumour cell death, applicability to a wider variety of cancers, and lowered risk of the emergence of therapy-resistant tumour cells.

More...

Bionomics to present BNC105 trial results of metastatic renal cancer at Asian Oncology Summit

New combination therapy holds promise for treating HER2-positive breast cancer

Resistance to therapy is a major problem in the cancer field. Even when a treatment initially works, the tumors often find ways around the therapy. Using human cell lines of the HER2-positive breast cancer subtype, researchers from the UNC School of Medicine and UNC Lineberger Comprehensive Cancer Center have detailed the surprising ways in which resistance manifests and how to defeat it before it happens.

The discovery, published today in the journal CELL Reports, provides the experimental evidence for the potential development of a novel combination therapy for HER2-positive breast cancer. The combination includes the FDA approved drug lapatinib (right structure) and a new experimental drug called a BET bromodomain inhibitor -JQ1 (see structure left), which works by disrupting the expression of specific genes.

 

This study, a collaboration of 20 University of North Carolina researchers, is the first time a BET bromodomain inhibitor has been shown to prevent the onset of resistance to drugs such as lapatinib in breast cancer cells.

"This research was done in cell lines of human HER2-positive breast cancer, not in patients; but the results are very striking," said Gary Johnson, PhD, Kenan Distinguished Professor and chair of the department of pharmacology, member of the UNC Lineberger Comprehensive Cancer Center, and senior author of the paper. "The combination treatments are currently being tested in different mouse models of breast cancer. Our goal is to create a new kind of therapy that could help oncologists make the response to treatment more durable and lasting for breast cancer patients."

Ref : http://www.nature.com/nature/journal/v468/n7327/abs/nature09504.html

New combination therapy holds promise for treating HER2-positive breast cancer

New high-throughput screening method may uncover novel treatments for kidney disease .

CKD affects more than 13% of adults in the United States, with diabetes, hypertension and atherosclerosis being common risk factors. Most patients rely on antihypertensive medications for treatment, and there are no therapies available that directly and specifically target the kidney.

A team led by Vineet Gupta, PhD and Jochen Reiser, MD, PhD (Rush University Medical Center) has now developed a system that can be used to identify novel drug candidates that protect the function of kidney podocytes, cells that are critical for filtering the blood. Damage to these cells is a hallmark of CKD.

"A key barrier to the rational development of podocyte-directed therapeutics has been a lack of cell-based assays for use in high-throughput drug discovery environment," said Dr. Gupta. "Our report describes what we believe to be the  first  podocyte  cell-based highcontent screening assay for the identification of novel podocyte-directed therapeutics in a high-throughput fashion."

Using the assay, which analyzes thousands of podocytes under different conditions in multi-well plates, the investigators identified 24 small molecules that protected podocytes against injury. When they treated mice and rats with one   of  the  molecules, called   pyrintegrin, the
animals' podocytes remained healthy despite being exposed to damaging agents.Pyrintegrin activates β1 integrin, a protein that acts as a molecular bridge to help podocytes hold onto the outside of blood vessels and maintain the filtration apparatus in the kidney.

"We believe that this assay could provide the much needed boost in fueling the discovery and development of kidney directed therapeutics, development of which has significantly lacked in recent times," said Dr. Reiser.

Ref : http://jasn.asnjournals.org/content/early/2015/04/09/ASN.2014090859

New high-throughput screening method may uncover novel treatments for kidney disease -- 

Allergy drug inhibits hepatitis C in mice

Chlorcyclizine (Di-Paralene,  Mantadil, Pruresidine, Trihistan) is a first-generation antihistamine of the phenylpiperazine class marketed in the United States and certain other countries. It is used primarily to treat allergy symptoms such as rhinitis,urticaria, and pruritus, and may also be used as an antiemetic. In addition to its antihistamine effects, chlorcyclizine also has some anticholinergic, antiserotonergic, and local anesthetic properties. It also has been studied as a potential treatment forhepatitis C.

The hepatitis C virus (HCV) causes liver inflammation and often leads to serious complications such as cirrhosis. Early diagnosis and treatment of HCV can prevent liver damage. Drugs are available to treat HCV, but costs can reach tens of thousands of dollars.

"Although hepatitis C is curable, there is an unmet need for effective and affordable medication," said lead author T. Jake Liang, M.D., senior investigator at NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). "CCZ is a promising candidate for part of a treatment regimen for this potentially life-threatening disease."

Conducted at the NIH campus in Bethesda, Maryland, the study found that CCZ blocked the early stage of HCV infection likely by impairing the ability of the virus to enter human liver cells grafted in the mice. The outcome was similar to that of commonly used antiviral drugs but without those drugs' toxic side effects.

"Using an innovative high-throughput screening process, we identified CCZ as a potent inhibitor of hepatitis C," said Anton Simeonov, Ph.D., acting scientific director of NIH's National Center for Advancing Translational Sciences (NCATS), which collaborated in the study. "Identifying already approved drugs from the NCATS Pharmaceutical Collection may offer a faster route to potential discovery of treatments for all diseases."

The researchers will next study how the drug affects people. CCZ is currently used for the treatment of allergies, not for HCV. "People should not take CCZ to treat their hepatitis C until it has been demonstrated that CCZ can be used safely and effectively for that purpose," cautions Liang.

Ref : http://stm.sciencemag.org/content/7/282/282ra49

Allergy drug inhibits hepatitis C in mice  

Enzalutamide: Indication of major added benefit for over 75-year-olds

In continuation of my update on enzalutamide

According to the findings, in comparison with watchful waiting the drug can prolong overall survival and delay the occurrence of disease complications. In men aged 75 years or older, IQWiG sees an indication of a major added benefit. There is also an indication of an added benefit in younger men; however, the extent is rated as "considerable."

Approval study terminated prematurely

The assessment was based on a randomized controlled trial (PREVAIL), which was the approval study for the indication described above. In this study, patients received either enzalutamide or a placebo, while the hormone-blocking medication was continued in all patients. In each study arm, treatment was continued until either the disease worsened (progression) or safety concerns arose, for example, because toxicity was too high.

As the interim analysis planned for the outcome "overall survival" had already shown good efficacy of enzalutamide, this was considered as the final Analysis.

Survival advantage depends on age

The difference in overall survival is statistically significant between the two study arms. However, as the further analysis of the data shows, this advantage is age dependent. It is greater in older men (75 years or more) than in younger ones. In each case, the IQWiG researchers derive an indication of an added benefit from these results, albeit with a different extent (major or minor).

Bone-related complications occur later

The study data also showed relevant group differences in favour of enzalutamide for other outcomes. For instance, bone-related complications occurred later in patients receiving enzalutamide than in those receiving placebo. IQWiG sees an indication of an added benefit here.

In addition, it took longer until opiates were used, that is, severe pain occurred later in patients receiving enzalutamide. This also applies to the occurrence of side effects (severe and serious adverse events) and the discontinuation of treatment due to side effects. Health-related quality of life also deteriorated later.

Enzalutamide: Indication of major added benefit for over 75-year-olds  

Nintedanib in lung cancer: Added benefit depends on disease severity

In continuation of my update on Nintedanib

According to the findings, there is an indication of a minor added benefit of nintedanib in combination with docetaxel in patients without brain metastases. However, in patients with brain metastases, the new drug has more disadvantages than chemotherapy with docetaxel alone. This results in a hint of a lesser benefit of nintedanib with the extent "considerable."

Findings from the only study are biased: at most indications can be derived

In its dossier the drug manufacturer compares treatment comprising nintedanib plus docetaxel with treatment comprising placebo plus docetaxel. As the treatment period in the nintedanib arm was longer than in the placebo arm (median: 4.3 versus 3 months), the observation periods for the study arms differed. Except for overall survival, the results are therefore uncertain for all outcomes.

In principle, at most an indication of an added benefit can be derived from the results of the only study included in the manufacturer dossier. As the analysis of the data shows, the advantages or disadvantages of nintedanib in combination with docetaxel primarily depend on whether patients already had brain metastases at the start of the study or not.

Patients without brain metastases live longer

Patients without brain metastases who received nintedanib in combination with docetaxel lived longer than study participants who were only treated with docetaxel (median: 13.5 versus 10.3 months). This results in an indication of a minor added benefit of nintedanib.

Although diarrhoea was more frequent in patients receiving nintedanib, this disadvantage does not challenge the survival advantage. Therefore, overall an indication remains of a minor added benefit for patients without brain metastases.

More symptoms in patients with brain metastases

Nintedanib in lung cancer: Added benefit depends on disease severity