Positive data on ability of MyoKardia’s MYK-461 to prevent development of HCM

Positive data on ability of MyoKardia’s MYK-461 to prevent development of HCM  

MyoKardia, Inc., a clinical stage biopharmaceutical company pioneering a precision medicine approach for the treatment of heritable cardiovascular diseases, today announced the publication of an article in the leading medical journal Science. The article demonstrates the ability of MYK-461, the company’s lead drug candidate, to prevent and reverse development of disease in multiple genetic mouse models of hypertrophic cardiomyopathy (HCM). The published research represents the product of collaboration among scientists from MyoKardia, Harvard Medical School, the University of Colorado and Stanford University. These data add to a growing body of laboratory and clinical research demonstrating the potential of MYK-461 as an important and novel approach to treating HCM.

The study, titled “A Small-Molecule Inhibitor of Sarcomere Contractility Suppresses Hypertrophic Cardiomyopathy in Mice,” will be published in the Feb. 5 issue of the journal Science.

“I am encouraged by these data that illustrate MYK-461’s ability to effectively reduce the consequences of HCM mutations at the biochemical, cellular and whole animal levels,” said Jonathan Fox, M.D., Ph.D., chief medical officer of MyoKardia. “Translation of these findings from mouse to human could offer great potential to improve the lives of patients living with this devastating disease.”

Bosutinib shows 'low' vascular, cardiac event risk profile

 In continuation of my update on Bosutinib

Third-generation tyrosine kinase inhibitor (TKI) study findings suggest that bosutinib is associated with a low risk of vascular and cardiac events in patients undergoing first-line or subsequent treatment for chronic myeloid leukaemia (CML).

"The results of this analysis suggest that the vascular and cardiac toxicity profile of bosutinib is distinct relative to other TKIs", write Jorge Cortes, from University of Texas MD Anderson Cancer Center in Houston, USA, and co-authors in the American Journal of Hematology

.

The team collated information on treatment-emergent adverse events (TEAEs) in 570 patients who received second-, third- or fourth-line bosutinib treatment for Philadelphia chromosome-positive CML as part of a phase I/II study.

In addition, the researchers determined the incidence of TEAEs in a phase III study comparing first-line bosutinib in 248 patients with first-line imatinib in 251 patients.

Trial participants were all followed up for at least 2 years and the overall incidence of vascular TEAEs was low, with all-grade and grade 3 or more severe side effects affecting 6.8% and 3.7% of patients given bosutinib, respectively.

First-line bosutinib was associated with a lower rate of vascular TEAEs than second-line or subsequent bosutinib therapy, affecting 4.8% versus 7.7%. First-line imatinib had comparable incidence of both overall and grade 3 and more severe vascular TEAEs to that of first-line bosutinib.

Cerebrovascular TEAEs were reported in 1.8% of patients given bosutinib, again being less common in those given primary bosutinib relative to second-line or later treatment (0.8 vs 2.3%). All-grade and grade 3 or more severe cardiovascular TEAEs occurred in 3.7% and 2.3% of bosutinib-treated patients, occurring at a lower rate in first-line than later treated patients (2.4 vs 4.2%).

Serious vascular TEAEs were reported in 4.2% of bosutinib-treated patients, with grade 3 or more severe events occurring in 3.1%, most commonly coronary artery disease (0.9%) and acute myocardial infarction (0.6%).

Events were less common in newly diagnosed patients than those with refractory or relapsed disease (2.0 vs 5.1%), and there was no significant difference in the incidence or exposure-adjusted rate between the first-line bosutinib and imatinib groups.

Ref : http://onlinelibrary.wiley.com/doi/10.1002/ajh.24360/abstract

Bosutinib shows 'low' vascular, cardiac event risk profile: Third-generation tyrosine kinase inhibitor study findings suggest that bosutinib is associated with a low risk of vascular and cardiac events in patients undergoing first-line or subsequent treatment for chronic myeloid leukaemia.

EC approves expanded use of Daklinza (daclatasvir) for patients with chronic HCV and HIV co-infection

Daclatasvir formerly BMS-790052, trade name Daklinza) is a drug for the treatment of hepatitis C (HCV). It was developed by Bristol-Myers Squibb and was approved in Europe on 22 August 2014. Daklinza gained its FDA approval on July 24, 2015 in the United States; it is approved for Hepatitis C genotype 3 infections.  

A generic version of daclatasvir is expected to be approved in India before the end of 2015. 

Daclatasvir inhibits the HCV nonstructural protein NS5A.  Recent research suggests that it targets two steps of the viral replication process, enabling rapid decline of HCV RNA. Daclatasvir has been tested in combination regimens with pegylated interferon and ribavirin,  as well as with other direct-acting antiviral agents including asunaprevir and sofosbuvir....

Now....

EC approves expanded use of Daklinza (daclatasvir) for patients with chronic HCV and HIV co-infection: Bristol-Myers Squibb today announced that the European Commission has approved the expanded use of Daklinza, a first-in-class oral, once-a-day pill used in combination with other treatments as an option for adult patients with chronic hepatitis C virus infection who are co-infected with HIV or who have had a prior liver transplant.

FDA-approved blood pressure drug reduces cell damage linked to Alzheimer's disease

In laboratory neuronal cultures, an FDA-approved drug used to treat high blood pressure reduced cell damage often linked to Alzheimer's disease, say researchers at Georgetown University Medical Center (GUMC) and the National Institutes of Health.

They say their work, published online Jan. 28 in the journal Alzheimer's Research and Therapy, provides information supporting the potential effect of the drug candesartan -- as well as other Angiotensin receptor blockers (ARBs) for the early treatment of Alzheimer's disease.

"Our findings make sense in many ways," says the study's senior author Juan M. Saavedra, MD, from GUMC's Department of Pharmacology and Physiology. "Hypertension reduces blood flow throughout the body and brain and is a risk factor of Alzheimer's disease. Previous epidemiological studies found that Alzheimer's progression is delayed in hypertensive patients treated with ARBs."

Using neuronal cultures, the researchers explored the action of candesartan on the neurotoxic effects of exposure to excessive glutamate, a demonstrated injury factor in the early stages of Alzheimer's disease.

The scientists found that candesartan prevented glutamate-induced neuronal death. They conducted in-depth gene analyses of the laboratory results, demonstrating that candesartan prevented neuronal inflammation and many other pathological processes, including alterations in amyloid metabolism, a hallmark of Alzheimer's disease.

The study's first author, Abdel G. Elkahloun, PhD, from the Comparative Genomics and Cancer Genetics Branch of the National Human Genome Research Institute, then compared gene expression in the neuronal cultures with published gene databases of autopsy samples from Alzheimer's disease patients. "The correlations were impressive -- the expression of 471 genes that were altered by excess glutamate in our cultures were also altered in brain autopsy samples from patients who suffered from Alzheimer's disease. Candesartan normalized expression of these genes in our cultures," Elkahloun says.

"We hypothesize that candesartan, or other members of the ARB group, may not only slow progression of Alzheimer's but also prevent or delay its development," Saavedra says.

FDA-approved blood pressure drug reduces cell damage linked to Alzheimer's disease: In laboratory neuronal cultures, an FDA-approved drug used to treat high blood pressure reduced cell damage often linked to Alzheimer's disease, say researchers at Georgetown University Medical Center and the National Institutes of Health.

Cystic Fibrosis Drug Seems OK for Preschoolers: Study

The cystic fibrosis drug ivacaftorappears safe and effective for young children, a drug company-funded study suggests.

Ivacaftor (trade name Kalydeco, developed as VX-770) is a drug approved for patients with a certain mutation of cystic fibrosis, which accounts for 4–5% cases of cystic fibrosis. Ivacaftor was developed by Vertex Pharmaceuticals in conjunction with the Cystic Fibrosis Foundation and is the first drug that treats the underlying cause rather than the symptoms of the disease. Called "the most important new drug of 2012", and "a wonder drug"  it is one of the most expensive drugs, costing over US$300,000 per year, which has led to criticism of Vertex for the high cost...

"This was a small trial, but we are thrilled to see these results," said study leader Jane Davies, from the National Heart and Lung Institute at Imperial College London in England. "Ivacaftor is a potential new treatment to offer children aged 2 years and older with cystic fibrosis and a [specific gene mutation linked to the disease]. This novel therapy could substantially impact these children's lives, potentially opening the way to even greater progress in years to come."

Cystic fibrosis is a life-threatening genetic disease that destroys the lungs and digestive system. More than 70,000 people worldwide have cystic fibrosis, the researchers said.

One expert explained that ivacaftor has been considered a big advance in the treatment of the disease.

"Ivacaftor, approved in 2012, was the first groundbreaking drug of its kind in that it works to correct the genetic defect in cystic fibrosis patients," explained Dr. Joan Decelie-Germana, director of the Cystic Fibrosis Center at Cohen Children's Medical Center in New Hyde Park, N.Y.

"For many older patients who have been taking it since 2012, they report feeling 'normal,' have no daily symptoms and lung function has stabilized or improved -- it has been a 'game changer,' " she said.

Prior studies found that ivacaftor was safe and effective in children 6 and older, as well as in teens and adults, the researchers said. However, this is the first study to assess the pill's effects in younger children, they added.

The clinical trial included 34 cystic fibrosis patients between the ages of 2 and 5. All of the youngsters had at least one copy of a mutation in a gene linked to cystic fibrosis called the CFTR gene. For six months, they took two daily doses -- 50 milligrams (mg) for children who weighed less than 14 kilograms (31 pounds) and 75 mg for those who weighed more.

The children showed improvement in several areas, including weight gain, pancreatic function and sweat chloride levels, which suggests an improvement in the body's ability to restore the balance of salt in and out of cells. When this process is defective, it leads to cystic fibrosis complications, the researchers said.

The drug was generally well-tolerated by the children, the study showed. The most common problems were coughing and vomiting. Five children had liver function abnormalities, leading one to stop treatment, the researchers said.

Funding for the study was provided by Vertex Pharmaceuticals Inc., maker of ivacaftor. The findings were published Jan. 20 in the journal Lancet Respiratory Medicine.

The study is "groundbreaking for cystic fibrosis care in children aged 2 to 5 years," wrote the authors of an accompanying editorial who are from University Children's Hospital Bern and University Children's Hospital Zurich, in Switzerland.

Cystic Fibrosis Drug Seems OK for Preschoolers: Study - Drugs.com MedNews

New Kidney Transplant Drug Cuts Risk of Earlier Death: Study

We know that, Belatacept (trade name Nulojix) is a fusion protein composed of the Fc fragment of a human IgG1 immunoglobulin linked to the extracellular domain of CTLA-4, which is a molecule crucial in the regulation of T-cell costimulation, selectively blocking the process of T-cell activation. It is intended to provide extended graft survival while limiting the toxicity generated by standard immune suppressing regimens, such as calcineurin inhibitors. It differs from abatacept (Orencia) by only 2 amino acids.

Belatacept was developed by Bristol-Myers-Squibb and approved by the U.S. Food and Drug Administration on June 15, 2011.

Now A newer drug used for preventing organ rejection might improve the long-term outlook for kidney transplant recipients, a new study finds.

Over seven years, patients given the drug belatacept (brand name: Nulojix) were 43 percent less likely to die or see their donor kidney fail compared to patients given an older drug called cyclosporine.

Experts said the findings should encourage more doctors and patients to choose belatacept over standard anti-rejection medications.

"This is a potentially transformational drug," said study lead researcher Dr. Flavio Vincenti, a transplant specialist at the University of California, San Francisco.

The study -- funded by the drug's maker, Bristol-Myers Squibb -- was published in the Jan. 28 issue of the New England Journal of Medicine.

Belatacept was first approved by the U.S. Food and Drug Administration in 2011 for preventing organ rejection after a kidney transplant. That was based on a three-year trial showing that the drug can prevent rejection in the shorter term, according to background information in the study.

Now the new findings prove what experts had hoped -- that belatacept would be better than cyclosporine in the long run, doctors said.

New Kidney Transplant Drug Cuts Risk of Earlier Death: Study 

Halaven Approved for Advanced Soft Tissue Cancer ...............

 

In continuation of my update on Halaven (eribulin mesylate)

Halaven (eribulin mesylate) has been approved by the U.S. Food and Drug Administration as the first chemotherapy drug shown to improve survival in people with advanced liposarcoma, a type of soft tissue sarcoma (cancer).

The drug is sanctioned for people who have received prior chemotherapy with a drug that contained anthracycline, the agency said Thursday in a news release.

Soft tissue sarcoma occurs when cancer invades soft tissues, such as muscles, tendons, fat, blood vessels, lymph nodes, nerves and tissues that surround joints, the FDA said. Liposarcoma specifically affects fat, most often of the head, neck, arms, legs, trunk or abdomen.

Halaven was evaluated in clinical studies involving more than 140 people with liposarcoma that had spread (metastatic) or couldn't be removed surgically. Average survival among people who took Halaven was 15.6 months, compared to 8.4 months among those who took another chemotherapy drug, dacarbazine.

The most common side effects of Halaven included fatigue, nausea, hair loss, constipation, nerve damage, abdominal pain and fever. Other adverse reactions included a drop in germ-fighting white blood cells and decreased levels of the minerals potassium or calcium.

More serious side effects included deadly infection, nerve damage, harm to a pregnant woman's fetus, and dangerous heartbeat abnormalities, the FDA said.

Halaven Approved for Advanced Soft Tissue Cancer - Drugs.com MedNews

Diet rich in fiber may reduce risk of developing lung disease

A diet rich in fiber may not only protect against diabetes and heart disease, it may reduce the risk of developing lung disease, according to new research published online, ahead of print in the Annals of the American Thoracic Society.

Analyzing data from the National Health and Nutrition Examination Surveys, researchers report in "The Relationship between Dietary Fiber Intake and Lung Function in NHANES," that among adults in the top quartile of fiber intake:

•68.3 percent had normal lung function, compared to 50.1 percent in the bottom quartile.

•14. 8 percent had airway restriction, compared to 29.8 percent in the bottom quartile.

In two important breathing tests, those with the highest fiber intake also performed significantly better than those with the lowest intake. Those in the top quartile had a greater lung capacity (FVC) and could exhale more air in one second (FEV1) than those in the lowest quartile.

"Lung disease is an important public health problem, so it's important to identify modifiable risk factors for prevention," said lead author Corrine Hanson PhD, RD, an associate professor of medical nutrition at the University of Nebraska Medical Center. "However, beyond smoking very few preventative strategies have been identified. Increasing fiber intake may be a practical and effective way for people to have an impact on their risk of lung disease."

Diet rich in fiber may reduce risk of developing lung disease: A diet rich in fiber may not only protect against diabetes and heart disease, it may reduce the risk of developing lung disease, according to new research published online, ahead of print in the Annals of the American Thoracic Society.

Sunitinib versus everolimus trial highlights non-clear cell RCC patient response heterogeneity

In continuation of my update on Sunitinib

Sunitinib offers significantly longer progression-free survival (PFS) than everolimus for patients with metastatic non-clear cell renal cell carcinoma (RCC), phase II trial results indicate, but treatment effect appears to depend upon key patient characteristics.

“Based on the present study and previous clinical studies, decisions on therapeutic choice between sunitinib and everolimus for patients with metastatic non-clear cell [RCC] should be based on prognostic risk criteria, histological subtype, and the known, expected side-effects”, say Andrew Armstrong, from Duke University in Durham, North Carolina, USA, and co-workers.

“Future clinical trials in these patients should also consider this heterogeneity of outcome when assessing novel agents”, they recommend in The Lancet Oncology. PFS was 8.3 months for the 51 patients randomly assigned to receive open-label, 6-week cycles of treatment with the VEGF receptor inhibitor sunitinib 50 mg/day compared with 5.6 months for the 57 patients given the mTOR inhibitor everolimus 10 mg/day, giving a significant hazard ratio (HR) of 1.41.

Sunitinib versus everolimus trial highlights non-clear cell RCC patient response heterogeneity: Sunitinib offers significantly longer progression-free survival than everolimus for patients with metastatic non-clear cell renal cell carcinoma, phase II trial results indicate, but treatment effect appears to depend upon key patient characteristics.

CGP3466B compound may effectively treat depression

We know that, Omigapil (TCH346 or CGP3466) is a drug that was developed by Novartis and tested in clinical trials for its ability to help treat Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). The development for PD and ALS have been terminated due to lack of benefit, but Santhera Pharmaceuticals bought the compound for development for the treatment of congenital muscular dystrophy (CMD). Omigapil was first synthesized at Ciba-Geigy, Basel, Switzerland. Santhera Pharmaceuticals has since taken over production of omigapil and preclinical trials for CMD. In May 2008, omigapil was granted orphan designation to commence clinical trials for. Pharmacokinetic trials are scheduled to commence enrollment in the second half of 2012 to determine the appropriate pharmacokinetic profile of the drug for children with laminin-α2-deficient congenital muscular dystrophy (MDC1A) and collagen VI related myopathy. Santhera Pharmaceuticals will use the phase 1 clinical trial to determine if the drug is safe and acts with the same pharmacokinetic profile in children as it does in adults. The impending clinical trial will take place in the United States at the National Institute of Neurological Disorders and Stroke/National Institute of Health(NNDCS/NINDS) (Bethesda, Maryland) and in the United Kingdom at Great Ormond Street Hospital (UCL

The compound CGP3466B, already proven nontoxic for people, may effectively and rapidly treat depression, according to results of a study in mice. The Johns Hopkins Medicine neuroscientists who conducted the research say that the compound -- previously shown to block cocaine craving in the brains of rodents -- delivers antidepressant effects to mice within hours instead of weeks or months, like currently available antidepressants. The results of the study will be summarized Jan. 12 online in the journal Molecular Psychiatry.

"One of the promising things about CGP3466B is that it targets a new network of proteins," says Solomon Snyder, M.D., professor of neuroscience at the Johns Hopkins University School of Medicine. "That means it may work in patients who are unresponsive to other types of drugs and it lays the foundation for the development of a new class of fast-acting antidepressants that target the same network."

The team's discovery came out of investigations into the workings of a different drug, ketamine, long used primarily at high doses to induce anesthesia during surgery but known, at lower doses, to be a fast-acting antidepressant. Unfortunately, Snyder says, ketamine is addictive and can produce schizophrenialike symptoms, making it unsuitable for prolonged use, but his team hoped it could shed light on how to make a better fast-acting antidepressant.

CGP3466B compound may effectively treat depression: 

Mylan announces launch of Linezolid Tablets, 600 mg in U.S.

In continuation of my update on Linezolid

Mylan N.V.  announced the U.S. launch of Linezolid Tablets, 600 mg, which is the generic version of Pfizer's Zyvox® Tablets. Mylan received final approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for this product, which is indicated in adults and children for the treatment of certain infections caused by susceptible Gram-positive bacteria.

Linezolid Tablets, 600 mg, had U.S. sales of approximately $457.8 million for the 12 months ending Sept. 30, 2015, according to IMS Health.

Currently, Mylan has 269 ANDAs pending FDA approval representing $100.8 billion in annual brand sales, according to IMS Health. Fifty of these pending ANDAs are potential first-to-file opportunities, representing $35.6 billion in annual brand sales, for the 12 months ending June 30, 2015, according to IMS Health.

Mylan announces launch of Linezolid Tablets, 600 mg in U.S.

UTA chemists design efficient water-based system for synthesis of organic compounds

Chemists at The University of Texas at Arlington have devised a safer, more environmentally friendly, less expensive and more efficient water-based system for the synthesis of organic compounds typically used in pharmaceuticals, agrochemicals, cosmetics, plastics, textiles and household chemicals.

Most organic synthesis depends heavily on volatile organic solvents, which typically pose significant environmental and health hazards and also are costly.

"Our new system could facilitate cheaper, safer and more efficient industrial reactions across a variety of sectors dependent on synthesis of organic compounds," said Morteza Khaledi, dean of UTA's College of Science and co-investigator of the project. "Using water as a solvent is ideal as it is benign, plentiful, cheap and not harmful to the environment."

The new medium, 80-90 percent water with fluoroalcohol, supports the synthetic reaction of organic compounds and even produces considerably higher yields of product than pure organic solvents.

The system also demonstrates the additional advantage that the mixture forms two separate phases during the reaction, which means that the resulting products can be easily separated and centrifuged out of the mixture. Typically, additional organic solvents are used to facilitate the separation and extraction of product.

"This is a clear step forward towards a "green" organic synthesis process and fits into UTA's strategic focus on Global Environmental Impact within the Strategic Plan 2020," Dean Khaledi said. "The organic solvent can even be recycled after the reaction, which is an additional bonus for the environment. "

UTA chemists design efficient water-based system for synthesis of organic compounds: Chemists at The University of Texas at Arlington have devised a safer, more environmentally friendly, less expensive and more efficient water-based system for the synthesis of organic compounds typically used in pharmaceuticals, agrochemicals, cosmetics, plastics, textiles and household chemicals.

New oral breast cancer drug has potential to combat other types of cancer

In continuation of my update on Palbociclib

Palbociclib, a new oral drug whose efficacy in combating breast cancer has been demonstrated alone and in combination with endocrine therapy, also has potential to combat other types of cancer, according to a literature review and additional original research conducted by experts at the Abramson Cancer Center (ACC) in the University of Pennsylvania published this month in JAMA Oncology.

Palbociclib targets the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6, which propel cell division and increase in number in most cancers. It is the first CDK4/6 inhibitor to be approved for the treatment of breast cancer.

"All living cells undergo cell division and palbociclib's unique capacity to halt the cell division process (also known as the 'cell cycle') therefore has potentially broad applicability," said the study's lead author Amy S. Clark, MD, MSCE, an assistant professor of Hematology/Oncology at Penn's Perelman School of Medicine and ACC. "Pairing palbociclib with other anti-cancer therapies such as endocrine therapy, chemotherapy, and targeted therapy can create a powerful combinatorial effect with real promise for addressing a variety of cancers." For example, amplification of CDK4 is reported in a high percentage of melanomas and esophageal cancers.

Targeted therapy uses medication and other interventions to more accurately identify and attack cancer cells, usually while doing no or little damage to normal cells.

"This drug has minor effects on normal cells other than neutrophils (white blood cells)," said the study's senior author, Peter J. O'Dwyer, MD, a professor of Hematology/Oncology at Penn and director of the Developmental Therapeutics Program at the ACC. "In tumors, it can cause shrinkage, or more commonly, arrest of growth. As we discover new functions for the CDK4/6 target of this medicine, we are likely to use it in combinations to make other anti-cancer agents work better."

New oral breast cancer drug has potential to combat other types of cancer

Potent parasite-killing mechanism of anti-malarial drug uncovered: New understanding of how artemisinin works could facilitate development of new drugs and therapeutic strategies against malaria -- ScienceDaily

In continuation of my update on artemisinin

A team of researchers has uncovered the mystery behind the potent parasite-killing effect of artemisinin, a drug that is considered to be the last line of defense against malaria. Given the emergence of artemisinin resistance, these findings could potentially lead to the design of new treatments against drug-resistant parasites.

Assistant Professor Lin Qingsong, who is from the Department of Biological Sciences under the NUS Faculty of Science and is one of the scientists who led the study, explained, "Many people may not realise that more human lives are lost to the tiny mosquito, more specifically malaria parasites, each year as compared to ferocious animals such as lions and sharks. After infection, malaria parasites, known for their blood-eating nature, can propagate inside the human body rapidly and consume up to 80 per cent of red blood cells in a short period of time, leading to a series of deadly symptoms."

About 3.2 billion people -- almost half of the world's population -- are considered to be at risk of malaria by the World Health Organization. As of September 2015, there were an estimated 214 million cases of malaria and 438,000 malaria-linked deaths this year alone.

Artemisinin and its derivatives are currently the most potent class of anti-malarial drugs. In recognition of its importance against malaria, the discovery of artemisinin won Chinese scientist Ms Tu Youyou the 2015 Nobel Prize in Physiology or Medicine earlier in October this year. While there have been extensive studies on artemisinin, the mechanism of the drug is not well understood.

Asst Prof Lin, together with Dr Wang Jigang, who was formerly with the NUS Department of Biological Sciences and now with the Singapore-MIT Alliance for Research & Technology, Associate Professor Kevin Tan from the Department of Microbiology and Immunology at the NUS Yong Loo Lin School of Medicine and their research team, discovered over 120 protein targets of artemisinin, and the mechanism that activates its deadly killing effect. The findings of the study are published in the journal Nature Communications on 23 December 2015.

Potent parasite-killing mechanism of anti-malarial drug uncovered: New understanding of how artemisinin works could facilitate development of new drugs and therapeutic strategies against malaria

New Breast Cancer Drug May Be Effective Against Other Types of Cancer, Abramson Cancer Center Experts Find

In continuation of my update on Palbociclib,

Palbociclib, a new oral drug whose efficacy in combating breast cancer has been demonstrated alone and in combination with endocrine therapy, also has potential to combat other types of cancer, according to a literature review and additional original research conducted by experts at the Abramson Cancer Center (ACC) in the University of Pennsylvania published this month in JAMA Oncology.

Palbociclib targets the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6, which propel cell division and increase in number in most cancers. It is the first CDK4/6 inhibitor to be approved for the treatment of breast cancer.

“All living cells undergo cell division and palbociclib’s unique capacity to halt the cell division process (also known as the ‘cell cycle’) therefore has potentially broad applicability,” said the study’s lead author Amy S. Clark, MD, MSCE, an assistant professor of Hematology/Oncology at Penn’s Perelman School of Medicine and ACC. “Pairing palbociclib with other anti-cancer therapies such as endocrine therapy, chemotherapy, and targeted therapy can create a powerful combinatorial effect with real promise for addressing a variety of cancers.” For example, amplification of CDK4 is reported in a high percentage of melanomas and esophageal cancers.

Targeted therapy uses medication and other interventions to more accurately identify and attack cancer cells, usually while doing no or little damage to normal cells. 

“This drug has minor effects on normal cells other than neutrophils (white blood cells),” said the study’s senior author, Peter J. O’Dwyer, MD, a professor of Hematology/Oncology at Penn and director of the Developmental Therapeutics Program at the ACC. “In tumors, it can cause shrinkage, or more commonly, arrest of growth. As we discover new functions for the CDK4/6 target of this medicine, we are likely to use it in combinations to make other anti-cancer agents work better.”

In addition to inhibiting the cell cycle, palbociclib has been shown, for example, to alter several recently described non–cell cycle functions of CDK4/6, a finding expected to expand its therapeutic role, O’Dwyer added.

Assessing 130 relevant publications in the literature, as well as interpreting their own continuing studies, the all-Penn team found that in addition to its safety and effectiveness in fighting certain types of breast cancer, early trials of palbociclib have shown promise of effectiveness in cases of lymphoma, sarcoma, and teratoma, tumors that while rare, often afflict younger patients.

A phase 2 trial showed that, among 17 patients with previously treated mantle-cell lymphoma, palbociclib resulted in one complete response and two partial responses. Although, median progression-free survival was four months, five patients had progression-free survival greater than one year. Another phase 2 trial with 29 sarcoma patients treated with palbociclib showed a progression-free survival of 66 percent at 12 weeks.

Also, combining palbociclib with other anti-cancer agents is feasible, and early results in myeloma and some solid tumors have led to more definitive studies.

New Breast Cancer Drug May Be Effective Against Other Types of Cancer, Abramson Cancer Center Experts Find