In Early Trial, Targeted Therapy Fights Advanced Melanoma

By probing deeper into the biological mechanisms that go awry in melanoma, scientists have come up with an experimental drug that has had an effect in a surprising number of patients with advanced melanoma.

The drug, PLX4032, just completed a phase 1 clinical trial in which 81 percent of participants with a particular gene mutation had a partial response, meaning at least some shrinkage of the tumor.

The current standard treatments for metastatic melanoma -- chemotherapy and interleukin-2 (IL2) -- only have response rates in about 15 percent of these patients, said Dr. Paul Chapman, senior author of a study in which the findings are described.

The average survival time for someone diagnosed with melanoma is nine to 11 months, added Chapman, who is an attending physician in the Melanoma Sarcoma Service at Memorial Sloan-Kettering Cancer Center in New York City.

One expert cautioned that it's too early to say whether the drug will actually prolong patient's lives, or if it might be helpful to patients in earlier stages of the disease.

"I don't want to say this is going to change survival rates but they're working with the most ill people, so you can't really generalize [to other patient populations]," said Dr. Alice Pentland, chair of dermatology at the University of Rochester Medical Center. "I think the most important part of this breakthrough is the bigger percentage of people who responded."

The study, which is published in the Aug. 26 issue of the New England Journal of Medicine, was funded by drug makers Plexxikon and Roche Pharmaceuticals.

About nine years ago, scientists discovered that the tumors of about half of patients with melanoma have a mutation in a gene called BRAF.

The gene appears to help drive the runaway cell division that is a hallmark of cancer. "It's always on. It's always signaling to the nucleus [of the tumor cells] that it's time to divide," Chapman explained.

That finding opened the door to potential targeted, molecular therapies for melanoma, which has been sorely lacking in effective treatments.

PLX4032 is the first potent inhibitor of BRAF that has made it to the clinical trial stage, Chapman said.

In the trial, 55 patients received escalating doses of the drug. Ten of 16 patients who had the BRAF gene mutation had a partial response to the drug, meaning the tumor shrank by at least 30 percent, while one had a complete response, with the tumor disappearing altogether.

Among 32 patients with BRAF-mutated melanoma in the second phase of the study, 24 had a partial response and two had a complete response.

"It worked: 81 percent had a partial response -- which has never been seen. I don't know of any solid tumors that have a response rate that high," said Chapman. "What's different here is that we've discovered a molecule that is responsible for driving the melanoma cell. It turns out that the melanoma really cares if we block the gene BRAF. It matters. It's addicted to this pathway."

There are some important caveats, however. It's not known at this time if the drug can improve overall survival, and a sizable proportion of participants developed resistance to the drug, the researchers say.

The findings join other recent reports of potential treatments for melanoma in what appears to be an exciting time for the field. Progress in this field has essentially been stalled for decades, experts say.

Recently, scientists reported that another experimental drug, ipilimumab, prolonged median survival in patients with metastatic melanoma from 6.4 months to 10 months.

"[Existing therapy] is not good for melanoma, so this is really a new opportunity that I think may have some importance to people," Pentland said.

However, she stressed that the best defense against melanoma is to get your skin examined regularly by a professional who knows what to look for.

"Our most successful treatment is to get [the lesion] early, get it before it's thick, get it before it spreads," she said.

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Findings May Lead to First Approved Treatment for Myelofibrosis

Myelofibrosis is a rare but serious disorder in which the bone marrow is replaced by scar tissue. There is no currently approved treatment for the disease, but a phase I/II clinical study of an experimental drug produced by Incyte Corp. of Delaware may possibly lead to the first medical option to reduce spleen size.

One of the primary symptoms of myelofibrosis is an enlarged spleen. Because the scarring of the bone marrow causes anemia, both the liver and the spleen attempt to make blood cells, which causes the organs to swell.

The new pill, called INCB18424 was found in a small study of 153 patients to reduce the size of the spleen of over half of the patients by 50% in an average of two weeks to one month, avoiding surgery to remove the organ called a splenectomy.

Also, fewer patients than expected progressed to a more severe form of the disorder called acute myeloid leukemia, a cancer that starts in the bone marrow and affects the normal production of white blood cells.

“This is a disease for which patients don’t have a therapy,” said Srdan Verstovsek, lead author and an associate professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center in Houston. The results, particularly the reduction of spleen size, have been “unbelievable,” he said.

The pill was also found to lessen other common symptoms, such as weight loss, fatigue and night sweats. Unfortunately, however, the medicine did not effectively address anemia, which in myelofibrosis patients often requires blood transfusions and medications called recombinant erythropoietin to help stimulate red blood cell production.

Incyte plants to initiate the third and final stage of human trials required for US approval of INCB18424.

If approved, the drug will likely be marketed by Novartis outside the US, according to Reuters.

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The FDA approves new drug for gout

The Food and Drug Administration said Tuesday that it has approved a new drug to treat gout in patients who do not respond to existing therapy. The drug is called Krystexxa and is manufactured by Savient Pharmaceuticals Inc. of East Brunswick, N.J. The FDA had rejected the drug in August of 2009 because of manufacturing problems.

In a letter to the company then, the agency said that the potential commercial supplies of the drug were not identical to the product used in clinical trials.

Gout occurs because of an excess of the metabolic waste product uric acid, which precipitates out of the bloodstream and into joints and soft tissue as needle-like crystals that can be very painful. They also cause intermittent swelling, redness, heat, pain and stiffness in the joints. Although most people tend to associate the disorder with rich foods, it is more commonly linked to obesity, high blood pressure, high cholesterol and diabetes. It is most common in men, post-menopausal women and people with kidney disease.

The conventional treatments include the drugs allopurinol and febuxostat, both of which inhibit the enzyme xanthine oxidase, which produces uric acid from DNA in food. Krystexxa, known generically as pegloticase, is an enzyme that acts directly on uric acid, converting it into harmless chemicals that are excreted in the urine. The drug is given by an intravenous infusion every two weeks.

"About 3% of the 3 million [American] adults who suffer from gout are not helped by conventional therapy," Dr. Badrul Chowdhury, director of the FDA's division of pulmonary, allergy and rheumatology products, said in a statement. "This drug offers an important new option for them."

But the agency cautioned that about 1 in every 4 patients receiving an infusion of the drug suffers a severe allergic reaction and urged physicians to give patients a corticosteroid and an antihistamine before infusing the drug.

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Scientists In Singapore Discover New Drug Against Malaria

Scientists from the Singapore Immunology Network (SIgN) of Singapore’s Agency of Science, Technology and Research’s (A*STAR) led by Dr Laurent Renia have made a breakthrough concerning a drug that is effective against malaria.

Their work, carried out with industry leader Novartis, the Swiss Tropical and Public Health Institute, and The Scripps Research Institute, was published in top scientific journal Science.

The discovery and validation of the new drug, spiroindolone NITD609, is timely as many strains of drug-resistant malaria are emerging.

Dr Renia and his team of scientists from SIgN played a significant role in the testing and validation of the drug. With the help of a pioneering technology, Dr Renia tested spiroindolone NITD609 against field isolates – samples of the parasite isolated directly from patients.

This enabled researchers to obtain a clearer picture of how the drug would perform in a real life situation. In addition, Dr Renia’s team also tested the drug against a strain of malaria, P. vivax, that cannot be cultured in a lab, showing that the drug was also effective against another important species of malaria parasites.

Said Dr Renia, “We are excited to be able to contribute to the fight against malaria with our expertise and know-how. Our technology enabled Novartis to obtain a clearer picture of how their drug might perform in the field, giving them a better idea of the effectiveness of their spiroindolone NITD609. Moving forward, we will continue to collaborate with Novartis in the necessary steps to bring the drug closer to a medical reality. ”

Prof Paola Castagnoli, Scientific Director of SIgN, commented, “Malaria is a threat that kills approximately one child every 45 seconds. This kind of collaboration between SIgN and Novartis represents how the talent and know-how of our researchers can be applied to problems as pressing and urgent as malaria. SIgN will continue to explore ways in which we can work together with the private sector (biotech and pharma companies) to fight against human infectious diseases.”

Dr Renia and his team plan to continue the fight against malaria by assisting Novartis in the further testing of other possible drug candidates against field isolates.

They are also planning to further develop SIgN’s expertise in technologies that can be used in the fight against malaria by developing a new, fast, and robust assay using portable flow cytometer to test drugs in field conditions

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New Drug Speeds Response in multidrug-resistant TB

Patients with multidrug-resistant TB (MDR-TB) given a new anti-TB drug -- TMC207 -- combined with a background regimen, responded almost twice as fast as those on placebo with the background regimen, a researcher reported here.

Final results from the first part of a stage IIb trial among 47 patients, found the median time to culture conversion was 11 weeks for those treated for eight weeks with TMC207 and the five-drug MBR-TB background regimen, according to Andreas Diacon, MD, of the University of Stellenbosch in South Africa.

In contrast, the median time for patients assigned to placebo combined with the five-drug background regimen was 18 weeks, Diacon reported here at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

"Importantly," Diacon said, "these patients were only treated with TMC207 for eight weeks and still there is a significant reduction in the median time to culture conversion compared with placebo."

The drug has been closely followed (See ICAAC-IDSA: Novel Drug Shows Power in MDR-TB) but Diacon presented the final results of the first stage of the trial, which involved eight weeks of therapy with TMC207 and two years of the background regimen alone.

A second stage of the trial, with a different and larger cohort of patients treated for 24 weeks, is currently under way, he added.

TMC207 interferes with synthesis of adenosine triphosphate in Mycobacterium tuberculosis cells, but not in other cells, even those of closely related bacteria. Inhibiting the compound reduces the energy available for the TB bacteria to combat other drugs or to reproduce.

The researchers were looking at the safety and tolerability of the drug, as well as efficacy, in 47 patients with multidrug-resistant TB, defined as a strain resistant to the first-line drugs isoniazid (Nydrazid) and rifampin (Rifadin).

They were treated with a five-drug background regimen, which varied from patient to patient but usually included ethionamide (Trecator), pyrazinamide, kanamycin (Kantrex), and ofloxacin (Floxin). TMC207 was given daily at 400 milligrams for two weeks, followed by 200 milligrams three times weekly for six weeks.

At the end of the first stage of the trial, Diacon said, 81% of those treated with TMC207 were considered cured, defined as two consecutive negative cultures at least 28 days apart and no recurrence of the disease.

In contrast, 57% of those getting the background regimen alone were considered cured, a difference that was significant at P=0.03, he said.

The drug was generally well tolerated, Diacon said. No patients stopped the drug because of adverse events, and the proportions of patients with grade 3 and 4 adverse events were similar between the arms -- 26% for TMC207 and 21% for placebo.

The results are exciting, according to Patrick Charles, MD, PhD, of Austin Health in Heidelberg, Australia, who moderated the session at which the study was presented but who was not involved in the research.

"It's really the first new drug to treat these extremely resistant cases," he told MedPage Today.

For patients with multidrug-resistant TB, he said, treatment options are "very limited and very expensive, so to have a new drug is very exciting."

According to the abstract, preliminary results from the second stage of this trial, involving 161 MDR-TB patients with TMC207 administered for six months, are expected soon.

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New drug hope for pancreatic cancer

A commonly used chemotherapy drug may offer a new lifeline to sufferers of one of the most deadly cancers, research has shown.

Trial results suggest that the drug 5-fluorouracil (5-FU) is an effective alternative for pancreatic cancer patients who fail to respond to standard treatment.

They also raise hopes of providing better therapy by combining the two drugs.

A study now under way is looking at the effect of prescribing a pill version of 5-FU with the more expensive standard chemotherapy drug, gemcitabine.

5-FU is currently used to treat a wide range of cancers including those affecting the bowel, breast and ovaries.

Almost 8,000 people are diagnosed with pancreatic cancer each year in the UK.

The disease is one of the hardest cancers to treat, and only around 3% of patients survive more than five years.

The new findings are published in the Journal of the American Medical Association (Jama).

Study leader Professor John Neoptolemos, director of the Liverpool Cancer Research UK Centre based at the University of Liverpool, said: "Until now the best way to treat pancreatic cancer has been unclear. But these results are the first to directly compare these two chemotherapies and show undoubtedly that they are both as effective as each other.

"Importantly this means patients now have a backup in case their cancer fails to respond to the first line of treatment. A new trial investigating whether combining these two treatments could be even more effective and prolong life is already under way and we look forward to seeing the result."

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Dapagliflozin is a new drug for the treatment of type two diabetes

A strange drug, the premier in its class, gives added blood sugar dominate to mobile vulgus with category 2 diabetes who are already enchanting the glucose-lowering medication metformin.

The budding agent, dapagliflozin, which also helped patients squander weight, is novel in that it does not produce directly on the body’s insulin mechanisms, according to a inspect appearing in the June 26 issue of The Lancet and slated for conferral at the annual gathering of the American Diabetes Association (ADA) in Orlando Noroxin. “It will likely be used as an add-on therapy,” said swotting lead author Clifford Bailey, a chemical pathologist and professor of clinical study at Aston University in Birmingham, UK “If you don’t unreservedly get to quarry with the maiden therapy tried , this approach would put on the market you an opportunity hopefully to maintain improved control”.

Bailey, who could not vaticinate if or when the drug might get final approval from cure-all regulatory authorities, also pointed out that dapagliflozin is flexible, message it can be used with various other treatments and at more or less any stage in the disease. “It’s a seemly add-on,” agreed Dr Stanley Mirsky, accomplice clinical professor of metabolic diseases at Mount Sinai Medical Center in New York City buy Tramaden. “is it a ask oneself drug? no. It may room a insufficient role”.

The con was funded by Bristol-Myers Squibb and AstraZeneca, which are developing dapagliflozin together. Dapagliflozin machinery by inspirational the kidneys to annihilate more glucose from the body via urine Actos. In this scrutiny of 534 adult patients with type 2 diabetes who were already irresistible metformin, the highest dispense of dapagliflozin (10 milligrams daily) was associated with a 0,84 percent diminish in HbA1c levels.

HbA1c is a compute of blood sugar control over time. Participants alluring 5 mg of the dope saw a 0,70 percent decrease in HbA1c levels, while those delightful 2.5 mg had a 0,67 percent decrease. In the placebo group, the subsidence in HbA1c was 0,3 percent, the haunt found.

Weight injury was also greater in volunteers winsome the study drug: 2,2 kilograms (4,8 pounds) in the 2,5 mg group; 3 kilograms (6,6 pounds) in the 5 mg group; and 2,9 kilograms (6,4 pounds) in the 10 mg group. Those in the placebo bunch misplaced 0,9 kilograms, or almost 2 pounds. Much, though not all, of this damage was like as not to be tap water weight, the authors stated.

There were more genital infections seen among those attractive dapagliflozin, the pair noted. “One of the complications of the poison is an enlargement in urinary tract infections or yeast infections because you have grave glucose levels in the urine,” said Dr Jacob Warman, boss of endocrinology at The Brooklyn Hospital Center in New York City. “That’s a very eulogistic way of life usual for yeast, so the endocrinologists aren’t too ecstatic about that”.

On the other hand, he said, this drug appears to run without some of the kidney, liver and muscle complications of other drugs so “it would be the best as an add-on to usual medications”. A assign study, also simultaneously being presented at the ADA encounter and published in The Lancet, found that adding inhaled insulin before each luncheon and long-acting insulin glargine before prevailing to bed worked just as well as engaging conventional therapy.

The regular psychotherapy consisted of taking biaspart insulin twice a day. This is a combine of short-acting insulin and intermediate-acting insulin. The altered regimen tangled less weight gain, fewer episodes of inadequate blood sugar and was more convenient, according to the study, which was funded by MannKind, the maker of Technosphere, the inhaled insulin featured in the trial.

A third burn the midnight oil found that once-weekly injections of the treatment Byetta (exenatide) worked better at controlling blood sugar levels than long-acting insulin. The training thus far has been to give Byetta twice a day. This study, funded by Amylin Pharmaceueticals and Eli Lilly, looked at a supplementary formulation of the drug buy generic sildenafil. Patients who got the once-a-week tone also perplexed an middling of 2,6 kilograms (5,7 pounds), the read found.

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Potential new drug for neurodegenerative diseases

A research team has identified a small molecule that helps human cells get rid of the misfolded, disfigured proteins implicated in Alzheimer's disease and other neurodegenerative ailments.

potential drug could have applications for other conditions as well.

Cells create and discard proteins continuously, a process that relies on a balance between the speed with which new proteins are created and damaged ones destroyed. Protein destruction occurs through a sophisticated system that marks proteins for disposal by tagging them with a small molecule called ubiquitin.

Ubiquitin latches onto these proteins, often forming long chains. The cell9s protein waste-disposal system, the proteasome, recognizes these ubiquitinated proteins and breaks them down.

If that finely tuned system malfunctions, damaged or misfolded proteins begin to accumulate in the cell and may become toxic. A number of ailments, including Parkinson's, Creutzfeldt-Jakob and Alzheimer9s have been linked to this build up of misfolded proteins.

To better understand just what causes this malfunction, a research team led by Harvard Medical School researchers Daniel Finley, professor of cell biology, and Randall King, associate professor of cell biology, zeroed in on an enzyme called Usp14.

They found that, when activated, Usp14 disassembles the ubiquitin chain, slowing down the proteasome's ability to rid the cell of bad proteins. As a result, the cell makes new proteins faster than it rids itself of the old ones, leading to a build-up of misfolded proteins.

The researchers wanted to see if they could find a molecule that inhibited Usp14, thus allowing the proteosome to work effectively. To identify such a selective inhibitor, Byung-Hoon Lee, a postdoctoral researcher, developed a special screening assay with assistance from the Institute of Chemistry and Cell Biology-Longwood Screening Facility at HMS.

Lee screened 63,000 compounds, looking for molecules that inhibited only Usp14 and could easily infiltrate the cell. The strongest candidate was a small molecule they named IU1.

Experimenting in both human and mouse cell cultures, Min Jae Lee, also a postdoctoral researcher, and his co-workers found that IU1 inhibited Usp14 and allowed the proteasome to dispose of proteins more quickly. In other words, adding IU1 to cells boosted proteasome activity.

Though scientists are still investigating just how IU1 works, it appears that the molecule suppresses Usp14's ability to trim the ubiquitin chain.

In addition to discovering IU1, this research has also shed light on an aspect of proteasome function that was not previously understood, King says.

Scientists had thought that the proteasome was not involved in regulating the speed of protein degradation, but that other proteins work with ubiquitin to modulate the process.

"Our work suggests that there is another level of control where the rate at which the proteasome can degrade these ubiquinated proteins is also controlled. It looks like there are multiple control steps along the way in this pathway," King said.

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New emergency contraceptive approved by FDA

The newest form of emergency contraceptive, ellaOne, was approved August 13 by the U.S. Food and Drug Administration.

Although the new drug has been around since fall of 2009 in select European countries, it was not introduced to the United States until June 2010.

The new drug is a type of emergency contraceptive pill that allows a woman up to five days after sexual intercourse to consume the pill.

The more popular contraceptive pill, Plan B One-Step, also known as the morning-after pill, offers only three days.

"The great thing about ellaOne is the efficacy lasts for all five days," said Morgan Molnar, '10, a marketing major pursuing her masters in sociology, who attended part of the first FDA hearing in June about ellaOne.

"The effects of the pill will be the same if you take it on the first day or the last day," she said. "If you take Plan B One-Step the day after unprotected sex, you will have a better chance of not getting pregnant than if you took the pill three days later. EllaOne lasts all five days and your chances don't decrease."

However, like most new drugs, long-term effects are unknown for ellaOne.

"As far as my opinion, it's a great drug, but my only concern is that it is so new," Molnar said. "They haven't done too many long-term studies, so in the case that women have become pregnant and have taken the drug, they don't know what will happen to the unborn fetus."

"Plan B One-Step doesn't have a lot of effects on the fetus, but ellaOne is so new that they are unsure of its effects in the long run," she said.

Susan Kitei, director of the Health Center, said she is not ready to endorse ellaOne because significant problems with a new medication are not always apparent until it has been widely used for two to five years.

"This is why, occasionally, we will hear on the news that a drug is being removed from the market," she said. "EllaOne has been used in Europe only since 2009, so it is wisest to wait a while to make absolutely certain it is as safe as other medications used for emergency contraception. The best alternative, Plan B, has been in wide usage for a number of years and is known to be safe and effective."

Kitei also said Plan B is available without a prescription for those 17 years and older.

The new drug will be prescription-only, and how its cost will compare with Plan B is still unknown.

"Since the decision of taking emergency contraception is such a big choice for women, this now gives them more time to make a good decision of whether or not they want to pursue with emergency contraception," Corry Starr, '13, said. "However," she said, "since ellaOne has to be prescribed, I don't think girls will want to use it as often as Plan B due to confidentiality."

"Based on what I saw, it looks like ellaOne is more effective than Plan B," Rita Jones, director of the Women's Center, said.

"It's advantageous because it offers women five days opposed to three days," she said.

"However, women should still think about securing emergency contraception as soon as possible. Just because they now have three to five days, doesn't mean they should simply wait around."

Karen Hicks, an adjunct professor of women's studies and sociology, also attended part of the first FDA hearing and recommended getting as much information as possible before using the medication.

"Time will tell how popular ellaOne will be in the U.S.," Kitei said. "The more educated a woman is, the less likely she is to need it. Because most of our students are aware of Plan B, I am expecting only rare requests."

Jones considered a separate advantage of the new drug and said the availability of the new drug is a benefit in cases of incest or sexual assault.

"In some incidents, the survivor might need a couple of days to process what happened," she said. "Five days provides more time for the survivor and helps them, as opposed to a smaller three-day window."

The price of ellaOne has yet to be determined in the United States but according to Molnar, it will be about three times the price of Plan B.

"I think the approval of ellaOne was definitely a step in the right direction toward giving women more choices," Molnar said.

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Promising Treatment for Metastatic Melanoma

Researchers from the John Theurer Cancer Center at Hackensack University Medical Center played an important role in a study that led to the Food & Drug Administration's (FDA) recent fast tracking of ipilimumab, a promising treatment for metastatic melanoma.

The FDA based its decision largely on the results of a pivotal study published in the New England Journal of Medicine on August 19, 2010 - the same day the agency accepted Bristol-Myers Squibb's application for the drug's approval and granted the application priority review status.

Ipilimumab is the first drug shown in randomized, placebo-controlled trials to improve survival in stage IV melanoma.

"This study, and the FDA's decision, provides new hope for people with this devastating cancer," said Andrew L. Pecora, M.D., F.A.C.P., C.P.E., Chairman and Executive Administrative Director, John Theurer Cancer Center, who led the study at the John Theurer Cancer Center. "We are proud to have played a role in helping move another promising cancer treatment closer to market."

The incidence of metastatic melanoma has increased over the last three decades, and the death rate continues to climb faster than that of most other cancers. According to the American Cancer Society, there were approximately 68,000 new cases of melanoma in the United States in 2009, and 8,700 melanoma-related deaths. Melanoma accounts for about three percent of all skin cancers, but 80 percent of skin cancer deaths. Melanoma is difficult to treat once it has spread beyond the skin to other parts of the body (metastasized). Very few treatment options exist for people with metastatic melanoma.

In this phase III study, researchers randomly assigned patients to one of three treatment groups: those receiving ipilimumab plus an inactive (placebo) version of gp 100, a cancer vaccine; those receiving ipilimumab plus gp 100; and those receiving gp 100 plus ipilimumab placebo. The treatments were administered once every three weeks, for a total of four treatments. The study was double blinded: neither the researchers nor the patients knew which medications the patients were being given.

To participate in the study, patients must have had stage III or IV (metastatic) melanoma, and must have been previously treated unsuccessfully with another cancer drug. They must also have had a life expectancy of at least four months. 676 patients participated in the study at 125 cancer centers.

Those who received ipilimumab, both by itself and with gp 100, lived a median of about 10 months, while those who received only gp 100 lived about 6.4 months. After two years, approximately 23 percent of those who got ipilimumab were alive, while 14 percent of those who did not receive this drug survived. Ten to 15 percent of those who received ipilimumab suffered attacks on their bodies' immune systems (autoimmune reactions), and seven of the 540 patients who got this drug died from these attacks. Most adverse events suffered by study participants, however, were reversible with treatment.

A monoclonal antibody, ipilimumab activates the body's immune system to fight cancer by blocking a protein called CTLA-4. CTLA-4 is a molecule on T-cells, white blood cells that play a critical role in regulating immune responses. CTLA-4 suppresses the immune system's response to disease, so blocking its activity stimulates the immune system to fight the melanoma.

The FDA grants priority review status to drugs that offer major advances in treatment, or that provide treatment where no adequate therapy exists. The projected FDA action date for the ipilimumab application is December 25, 2010.

The John Theurer Cancer Center has more than 100 clinical trials under way for all types of cancer and life-threatening blood disorders. Clinical trials test the safety and effectiveness of new medications, therapies, treatment regimens, devices, and adjuvant treatments in human patients. These clinical trials are conducted independently or in cooperation with pharmaceutical companies, universities, other cancer centers, and national organizations such as the National Cancer Institute, the American Cancer Society, the National Science Foundation, and the National Institutes of Health.

"Our commitment to providing outstanding patient care and leading edge treatments extends to our leadership or participation in major clinical trials," said Dr. Pecora. "We are dedicated to improving treatment outcomes not just for our patients, but for all of those with cancer."

Results of this study were originally presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2010, and published online by the New England Journal of Medicine to coincide with the presentation.

About the John Theurer Cancer Center at Hackensack University Medical Center

The John Theurer Cancer Center at Hackensack University Medical Center is New Jersey's largest and most comprehensive center dedicated to the diagnosis, treatment, management, research, screenings, and preventive care as well as survivorship of patients with all types of cancer. The 15 specialized divisions covering the complete spectrum of cancer care have developed a close-knit team of medical, research, nursing, and support staff with specialized expertise that translates into more advanced, focused care for all patients. Each year, more people in the New Jersey/New York metropolitan area turn to the John Theurer Cancer Center for cancer care than to any other facility in New Jersey. Housed within a 775-bed not-for-profit teaching, tertiary care, and research hospital, the John Theurer Cancer Center provides state-of-the-art technological advances, compassionate care, research innovations, medical expertise, and a full range of after care services that distinguish the John Theurer Cancer Center from other facilities.

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Merck-Cardiome heart rhythm drug meets study goals

Merck & Co. and Cardiome Pharma Corp. said Friday that their drug candidate Brinavess met its goal in a late-stage clinical study, as it was better at restoring a steady heartbeat than an older drug use for the same purpose.

The trial compared Brinavess to the standard drug, amiodarone, as a treatment for atrial fibrillation. Atrial fibrillation is a condition in which the upper chambers of the heart beat rapidly and ineffectively. Merck and Cardiome said more than half the patients treated with Brinavess had a normal heart rhythm within 90 minutes, compared to about 5 percent of the amiodarone patients.

The companies said 51.7 percent of Brinavess patients had a normal heart rhythm within that time, and the median time to normal heart rhythm was 11 minutes. They said 5.2 percent of the patients who were treated with amiodarone met that goal. After 90 minutes, 53.4 percent of the Brinavess patients had no symptoms, compared to 32.8 percent of the amiodarone group.

Brinavess is an intravenous version of vernakalant, a drug Merck and Cardiome have been developing together. The companies have filed for approval in the U.S. and the European Union, and they are also working on an oral form of the drug. If approved, Brinavess would compete with Sanofi-Aventis' drug Multaq, which was approved in 2009.

A total of 232 patients were treated in the study, and Merck and Cardiome said the Brinavess patients also had a greater quality of life improvement based on a survey. The most common side effects of Brinavess were a bad taste in the mouth, coughing, sneezing, atrial fibrillation, nausea, dizziness, and high blood pressure.

Results from the trial were presented at a Heart Rhythm Society meeting in Denver.

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Trials begin on hepatitis C drug

The first human clinical trials have started on a new drug developed to treat infections caused by the hepatitis C virus.

The medication, taken orally, was first prepared at the Welsh School of Pharmacy at Cardiff University in 2008.

Laboratory tests showed it killed 90% of the virus at very low concentration.

Trials in healthy volunteers to assess the drug's safety are being held before its effectiveness on patients is tested in trials next year.

Approximately 170m people around the world are affected by hepatitis C, which can lead to liver cancer and cirrhosis and can be fatal.

It is the leading cause of liver transplantation in western countries.

The current treatment involves two drugs - ribavirin and interferon, which has to be given as an injection.

Side effects are often severe and lead to patients failing to complete the treatment.

However, researchers at the university believe the new drug, INX-189, is one of the most potent of its kind developed to date.

US pharmaceutical company Inhibitex, which owns the licence to INX-189 and has been working with the Cardiff team, is running the trials.

'Encouraging progress'

Professor Chris McGuigan, of the Welsh School of Pharmacy, who is the academic lead on the project, said the trials were in a "a very early stage".

"However, progress has been encouraging so far, going from the laboratory to human trials within 18 months.

"We believe that INX-189 offers the possibility of more potency against hepatitis, more rapid action in the liver, and fewer side effects than existing treatments."

Cardiff University and Inhibitex filed a patent on INX-189 earlier this year. It has been cleared for human clinical trials by the Food and Drug Administration in the US.

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New drug type developed to kill lymphoma cells

Scientists have developed a new type of drug designed to kill non-Hodgkin lymphoma tumour cells.

The breakthrough could lead to potential non-toxic therapies for cancer patients.

The researchers, including Dr. Ari Melnick, of Weill Cornell Medical College, Dr. Alexander MacKerell, of the University of Maryland and Dr. Gilbert Prive, of the University of Toronto, have identified a drug that targets an oncogene known as BCL6.CL6 functions as a master regulatory protein.

"It's a protein that controls the production of thousands of other genes. Because of that, it has a very profound impact on cells and is required for lymphoma cells to survive and multiply," said Melnick.

BCL6 causes the majority of diffuse large B cell lymphomas, the most common form of non-Hodgkin lymphoma.

Currently, about 60 percent of diffuse large B cell lymphomas can be cured with chemo-immunotherapy, said Melnick.

"The hope is that we can improve that to a higher percent, and in the long term reduce the need for chemotherapy," he added.

Traditional cancer drugs target enzymes, which have small pockets on their surfaces that can be blocked with molecules.

Until now, pharmaceutical companies have been reluctant to create drugs that target a protein like BCL6 because they function through a different mechanism involving interactions with cofactor proteins involving extensive protein surfaces.

"And because the real estate covered by these interactions is so large, the drug companies have viewed these as being not druggable targets," said Melnick.

The researchers could identify a "hot spot" on BLC6 that they predicted would play a critical role in protein interactions.

They showed that their BCL6 inhibitor drug was specific to BCL6, and did not block other master regulatory proteins.

The drug had powerful lymphoma killing activity and yet was non-toxic to normal tissues.

"This is the first time a drug of this nature has been designed and it shows that it's not actually impossible to target factors like BCL6," he said.

Emerging data from other investigators suggests that BCL6 is important in many other tumor types, including forms of leukemia.

The study has been published in a recent issue of Cancer Cell. (ANI)

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Additional Data From Phase 1b Study Of Hepatitis Drug Shows Positive Results

Biopharmaceutical company Achillion Pharmaceuticals Inc. said Tuesday that an additional preliminary data from its Phase 1b clinical trial of HCV Protease Inhibitor demonstrated positive results, with meaningful reductions in Hepatitis observed, and accompanied by continued safety and tolerability levels. Following the disclosure, the company's share were up 17.37% in the after hours trade.

Hepatitis C virus is the most common cause of viral hepatitis, an inflammation of the liver, and is currently estimated that more than 170 million people are infected with HCV worldwide.

ACH-1625 is an inhibitor of HCV NS3 protease that was discovered, and is being developed by Achillion. In preclinical studies, ACH-1625 demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures.

Now with the Phase 1b study, Achillon said the additional data revealed that both the third and fourth patient cohorts receiving treatment with ACH-1625 achieved meaningful reductions in HCV RNA after a five-day monotherapy.

Achillon said that results from its Third Dosing Cohort with 9 subjects, administered 200 mg twice daily over a 5 day period, showed a mean maximum reduction in viral load of 3.86 log10, compared with a mean rise of 0.16 log10 in the placebo group. Also, all subjects in the treatment group had a viral load decline greater than than 3.0 log10, and that there were no serious adverse events, and no clinically significant changes in vital signs, or laboratory evaluations. All adverse events in patients receiving ACH-1625 were classified as mild or moderate and were transient, with sustained viral suppression observed, the company added.

Further, the company said that the Fourth Dosing Cohort, with 8 subjects on a 600mg once daily dosage for five days, showed a mean maximum reduction in viral load of 3.81 log10 was achieved in the treatment group, compared with a mean rise of 0.24 log10 in the placebo group. Achillon stated that, all subjects in the treatment group had viral load decline greater than 3.0 log10, and that safety results were similar to those observed in previous segments of the trial. However, Achillon added, there was one non-drug-related serious adverse event, a bone fracture in a patient receiving placebo, but there were no clinically significant changes in vital signs, or laboratory evaluations. All reported adverse events in patients receiving ACH-1625 were classified as mild or moderate and were transient, with sustained viral supression observed.

Chief Executive Officer Michael Kishbauch said " It is impressive that at all dose levels ACH-1625 has shown meaningful viral load reduction and sustained viral suppression post treatment course. Importantly, we believe the results from these last two cohorts demonstrated that ACH-1625 was effective at a lower dosing level and in a once-daily dose, features that distinguish our drug and suggest it could offer improvements over other protease inhibitors currently in development.

If the results are sustained through further development, then ACH-1625 would contend as a potential best-in-class protease inhibitor, Kishbauch added.

Earlier, in Phase 1a safety studies with ACH-1625, where subjects were exposed to both single ascending dose, and multiple ascending dose, preliminary data demonstrated ACH-1625 was well tolerated at all doses and there were no serious adverse events, and no clinically significant changes in vital signs, and adverse events were classified as mild or moderate.

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New drug may help MS patients walk

A new drug may make getting around easier for the 2.5 million people worldwide afflicted with multiple sclerosis. It is the first medication to specifically target walking challenges faced by MS patients.

In January, the U.S. Food and Drug Administration approved Ampyra (dalfampridine) as an oral medication to improve walking in people with MS. It has been available by prescription since March 1.

The drug holds promise for Chris Messina, who misses strolling around the Staten Island Mall, and Danielle Mino, who can’t always keep up with her two young children.

Both Great Kills women have MS, a chronic disease that affects the central nervous system and can make walking a daunting experience.

Since April 21, Mrs. Messina has been taking one 10-milligram tablet of Ampyra twice a day. She’s been told it may take up to three months to experience results.

“I wait for a difference every day,” said Mrs. Messina, a 54-year-old former radiology clerk at Staten Island University Hospital.

Diagnosed in 1975, her ability to walk deteriorated about eight years ago during a relapse from which she never regained her former mobility.

“When I walk, I stumble, I trip, I walk crazy. I go back and forth and swagger,” said Mrs. Messina. “I used to live at the mall, but since I’ve been like this I haven’t been there in years.”

In two clinical trials of 540 MS patients in the United States and Canada, those treated with Ampyra had faster walking speeds on timed 25-foot walks than those given a placebo, according to Acorda Therapeutics, Inc., the Hawthorne, New York-based developer of the drug. Those whose walking speed improved, also noted an improvement in leg strength.

While the measuring stick for improvement may seem small, to those who live with MS, the trial’s findings are huge.

“My leg kind of drags a little, I don’t really have too much balance or strength especially in my right leg,” said Mrs. Mino, a 40-year-old mother of a 5½-year-old daughter and 4-year-old son.

“On a good day I can get up, get my children ready for school and then do what I have to do, cleaning, food shopping,” she explained. “But on a bad day, I just get my kids ready for school, put them on the school bus and then I just sit down most of the day.”

Ampyra is taken with other MS drugs and does not keep MS from getting worse. There is no cure for MS.

Both Mrs. Messina and Mrs. Mino are infused with Tysabri — a disease modifying medication that helps prevent relapses of MS symptoms — every four weeks at the MS Center of Staten Island in New Dorp.

“Ampyra is a symptomatic medicine. It makes you walk better, move better, but it doesn’t affect the disease itself,” said Dr. Allan Perel, director of the MS Center.

“You can still have attacks with it. You could still have progressive neurological findings. The MRIs could look worse.”

So far, more than 2,000 U.S. physicians have written at least one prescription for Ampyra, said Jeff Macdonald, a spokesman for Acorda. The MS Center has about 100 patients who have been prescribed the new drug, said Perel.

Ampyra is a potassium channel blocker which is believed to improve the transmission of nerve signals in nerve fibers whose insulating coating has been damaged by MS.

The tablets work as a timed-release formulation of dalfampridine, which was originally used as a seizure-inducing bird-control repellent.

For more than two decades, dalfampridine has been compounded in pharmacies and used off-label to treat people with various neurologic conditions.

While the FDA approved the use of Ampyra for people with any type of MS, it should not be taken by individuals with a history of seizures, or by those with moderate to severe kidney problems.

According to the FDA, when Ampyra is given at doses greater than 10 milligrams twice a day, it can cause seizures. The most common side effects reported by patients taking Ampyra in clinical trials included urinary tract infections, insomnia, dizziness, headache, nausea, back pain and balance problems.

The price of Ampyra is $1,056 for a 30-day supply (two tablets per day). It is only available by mail order through a network of specialty pharmacies that work with Acorda.

The drug’s hefty price is being offset by Acorda, which has developed assistance programs to help MS patients afford the drug.

Mrs. Mino is currently waiting for her prescription of Ampyra to arrive. Diagnosed with MS in 1999, she hopes the drug will make it easier to do activities like going on vacation with her children.

During a November trip to Disney World, trekking between attractions was especially challenging for her.

“It was so hard trying to walk through the park. At least every 10 minutes I would have to stop,” said Mrs. Mino. “Whenever we had to wait on a line for a ride, I was happy because I didn’t have to do any more walking.”

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Ralfinamide fails in Serena study on NLBP patients

Newron Pharmaceuticals SpA, a research and development company focused on novel CNS and pain therapies, has announced that the topline top-line results of its Serena study, a phase-IIb/III study of ralfinamide in patients with at least moderate Neuropathic Low Back Pain (NLBP) failed to show any significant difference between ralfinamide and placebo.

The 12-week Serena study enrolled 411 patients with chronic NLBP of at least moderate severity and evaluated the safety and efficacy of two dose regimens of ralfinamide compared to placebo. Available results on the primary endpoint of the study, the change from baseline for the 11-point Likert Scale, did not detect any significant difference between ralfinamide and placebo. Ralfinamide was well tolerated, with no clinically significant differences from placebo on safety measures.

Further analyses of the additional endpoints (VAS, PGI, CGI etc) are currently ongoing and will be reviewed with Newron’s external advisors. Based on the multiple CNS effects seen in animal pharmacology models, and the excellent human safety data, Newron will decide how to proceed further with the compound.

Luca Benatti, Newron´s chief executive officer, commented, “We are extremely surprised and disappointed by the results, based on the statistically significant benefits shown in a phase II placebo-controlled trial, as well as the results from a large number of preclinical studies. We shall be working with our external advisors to make a complete assessment of the data prior to determining our next steps, including a review of our development resource needs going forward. We have a broad portfolio of products in various stages of development, addressing substantial market opportunities and this, combined with our existing cash resources and SEDA equity line, gives Newron continued potential for growth and value generation.”

In addition to ralfinamide, Newron has an advanced pipeline of innovative compounds, that include safinamide, currently in phase-III development for the treatment of Parkinson’s disease (add-on treatment for all stages of PD) together with Merck Serono; NW-3509, an novel treatment for schizophrenia expected to enter human trials later this year, and HF0220, a potential disease-modifying therapy for neurodegenerative disorders, currently in phase-II.

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Potential new drug target to combat Kaposi's Sarcoma

Kaposi's Sarcoma is a cancer caused by a human herpes virus and is widespread in sub-Saharan Africa, where it is the most common cause of cancer amongst those infected with HIV.

Researchers from Leeds' Faculty of Biological Sciences found that a human protein - known as PYM - is hijacked by the virus to help it replicate. A virus-encoded protein, ORF57, interacts with PYM and when this interaction was blocked during molecular experiments, the virus was unable to replicate. The findings are published today in The EMBO Journal.

"This is the first time that the cellular protein, PYM, has been shown to play a role in virus replication and Kaposi's Sarcoma," explains Dr Adrian Whitehouse, who led the research. "Our work is still at a very early stage, but it should in time be possible to design drugs which block the interaction between PYM and the virus protein, thereby stopping the virus replicating and hopefully stopping the cancer from developing."

Kaposi's Sarcoma-associated herpesvirus is an opportunistic infection which is most prevalent amongst people with a weakened immune system, such as those infected with HIV. Treatment for KS does exist but currently involves chemotherapy and highly active antiretroviral therapy which is both toxic and not always effective. Moreover, such combined therapies are only available to a small percentage of those affected in sub-Saharan Africa and other parts of the developing world.

The researchers - funded by the Wellcome Trust and BBSRC - are now looking to obtain the structure of these two interacting proteins, as the next step towards designing an anti-viral drug to combat the disease.

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FDA approves new oral contraceptive

The U.S. Food and Drug Administration, FDA, has approved a new oral contraceptive for women called Natazia. The new drug contains two female hormones, estrogen and progestin.

Scott Monroe, M.D., director of FDA's Division of Reproductive and Urologic Products reports, “Nearly 12 million women in the United States and more than 100 million women worldwide currently use oral contraceptives. The approval of Natazia provides another option for women who choose to use an oral contraceptive as their method of contraception.”

The most common side effects include irregular bleeding, breast tenderness, headaches, nausea, vomiting, increased weight, and acne. Women over 35 years of age who smoke are being advised to not use Natazia. Evidence has shown that cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use.

In Michigan, over one million women are in need of contraceptive services and supplies. Over 213,000 of the over 2 million women of childbearing age become pregnant each year. Natazia becomes another choice women can make in contraception use.

Manufactured by Bayer Schering Pharma, Natazia is expected to be available by this summer in the U.S.

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New drug offers hope to Celiac sufferers

Even if Janet Smith could give her 13-year-old daughter, Heather, a drug that would let her eat gluten, she wouldn’t necessarily do it.

The Brooklin mom has been monitoring everything Heather eats since she was an infant, making her special foods and keeping her on a strict, gluten-free diet. It hasn’t been easy — the slightest trace of gluten can make Heather sick for weeks — but Smith isn’t convinced that a drug would be better.

“We’ve followed this path for so many years,” she says. “She’s never eaten regular foods, so for her to take a pill and be able to eat what we eat would be a total adjustment for her.”

Heather was diagnosed with celiac disease when she was 14 months old. Eating gluten, a protein found in wheat and other grains, damages the lining of her intestinal tract and suppresses her body’s absorption of vitamins and minerals such as iron, calcium and vitamin D.

Many doctors mistakenly think the disease is rare, says Shelley Case, a dietitian on the board of the Celiac Disease Foundation and the Canadian Celiac Association, and the author of Gluten Free Diet (Case Nutrition, 2010). The reality is that an estimated one in 133 people are affected, and most don’t even know it.

“If I could pass along one message to readers, it’s that around 95 per cent of the people who have celiac disease are not diagnosed,” says Janet Dalziel, president of the Canadian Celiac Association and herself a sufferer of the disease.

There is no cure for celiac disease, nor any treatment beyond removing all traces of gluten from your diet. But a new drug could be a partial solution.

Called Larazotide Acetate, the drug is being tested in 11 cities — including by University of Alberta researchers in Edmonton, the only Canadian city involved in the study. A fourth clinical trial starts later this year, but researchers say the results look promising and the drug could be available by 2012.

The drug essentially blocks gluten from being absorbed into the intestines and causing damage, which would make it possible for celiacs to eat bread, cake, pasta and other foods containing gluten without any ill effects.

So, why isn’t Smith and other sufferers of celiac disease on board?

“Any time someone mentions a drug, the next questions are going to be ‘How much is it going to cost?’ and ‘What are the side effects?’” says Case. “Patients do so well on the gluten-free diet that they often aren’t interested in trying anything else.”

“Heather’s still so reactive,” says her mom, “that I don’t know if she’d be comfortable with a medication.”

Heather had just started eating solid food as an infant when she started vomiting eight or nine times a day and had constant diarrhea. A pediatrician misdiagnosed her with stomach flu. “She was 10 pounds at birth and, at 18 months, she was only 15 pounds,” says Smith. “She had very skinny arms and legs, but then she had this absolutely enormous stomach. I couldn’t even keep pants on her. She had to wear little dresses because the pants wouldn’t stay up over her diaper.”

So Smith sought a second opinion — a pediatrician who, by coincidence, was also a gastroenterologist. “I said, ‘Could you just look at her without any clothes on?’ ” recalls Smith. The second doctor diagnosed Heather right away; a blood test and biopsy confirmed the diagnosis.

Adults might have an easier time adjusting to a medication, suggests Smith, who also volunteers with the Canadian Celiac Association and runs the Toronto chapter of a support group called R.O.C.K. (Raising Our Celiac Kids).

Now that Heather is a teenager, Smith can already foresee new challenges. “When you’re a kid, it’s cool to be different,” she says. “Now, we’re entering a phase where it’s embarrassing for her. She doesn’t want to have to eat special food. She wants to be like her friends.”

Dalziel, too, is hesitant about medication. “A lot of us wouldn’t consider it as a replacement for the diet,” she says.

Instead, Dalziel might consider using it to safeguard against accidental exposure or on special occasions — say, once a year, so she could eat ordinary birthday cake. “Some people are so afraid of getting ill that they probably wouldn’t risk it. They’re so adapted to the gluten-free diet that it’s like religion for them.”

Her own diagnosis, when she was in her mid-50s, came as a shock — she’d never heard of celiac disease and had gone to her doctor complaining about chronic fatigue.

“For years, I blamed it on my stressful job, as the vice-principal of a secondary school,” says Dalziel, who calls it a miracle that her doctor thought of getting her tested for malabsorption of nutrients, a consequence of celiac disease.

Her quick diagnosis isn’t the norm — most sufferers spend years searching for an answer to symptoms that can range from constipation and diarrhea to migraines and joint pain, or from low iron and abnormal weight changes to night blindness and infertility. Research shows that the average lag time between when symptoms first appear and when celiac disease is diagnosed is 11.7 years.

In fact, Smith might soon be on a gluten-free diet herself. Although she’s never had symptoms, she was tested 13 years ago when her daughter was diagnosed, and the results came back false-positive. Her doctor recently suggested she get tested again. This time, her results came back abnormal.

“Here I am, a totally healthy person,” says Smith. “I feel good all the time, but inside, that’s the problem — you can’t see what’s happening to your small intestine.”

But she is thankful for the diagnosis. “It’s so easily treated. Once you get on the gluten-free diet, you heal and you’re as good as new.”

Do you have celiac?

Could you be among the 95 per cent of undiagnosed cases of celiac disease? With the disease affecting one in every 133 people, it’s something to think about.

There’s no telling how the disease will affect you. Symptoms vary wildly from patient to patient, ranging from constipation and diarrhea to fatigue and migraines or from low iron and joint pain to night blindness and infertility.

People are often diagnosed with anemia or osteoporosis before they are diagnosed with celiac disease, because the disease sabotages the body’s ability to absorb nutrients.

Celiac disease can be inherited, so if a family member has the disease, or a related illness such as Type I diabetes, anemia or osteoporosis, mention it to your doctor.

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Osiris to resume enrollment in Crohn's drug study

Osiris Therapeutics Inc said it is resuming enrollment of patients in a clinical trial to study its lead drug Prochymal in patients with treatment-resistant Crohn's disease, sending its shares up 5 percent in after-market trade.

Data from an interim analysis showed that for the primary endpoint of disease remission, the drug approached statistical significance in the intent to treat population, the adult stem cell research firm said in a statement.

The drug also reached significance in the per protocol population, it added.

Enrollment for the Crohn's program, consisting of two linked trials, was suspended last year over concerns over the trial design.

The decision to resume enrollment was made following discussions with the Food and Drug Administration about the results of the interim analysis, the company said.

Crohn's disease is a chronic inflammatory condition of the gastrointestinal tract that affects almost one million people in the United States.

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