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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Ticagrelor : New hope for heart attack patients

A major drug trial has brought scientists closer to making a drug that could prevent thousands of deaths from heart attacks.

From the past six years, international clinical trials have been going on a new drug, ticagrelor.

The new findings have revealed that the platelet function in patients taking ticagrelor recovered much quicker after the drug is stopped, compared to the current gold standard drug, clopidogrel.

This study has also confirmed that breathlessness occurs as a side effect of ticagrelor but this is not associated with any harmful effects on lung or heart function.

The findings also include a new analysis of a previous trial looking at ticagrelor.

This new examination of the Plato trial, which was completed last year, showed that ticagrelor prevents 1 in 5 deaths after a heart attack, and patients who develop the adverse effect of breathlessness with ticagrelor still benefit from a lower risk of death compared to patients treated with clopidogrel for one year following a heart attack.

This has also confirmed that patients treated with clopidogrel, who have a genetic variant that reduces the effect of this drug have a slightly higher risk following heart attack but ticagrelor is not affected by this variant and is still more effective than clopidogrel, regardless of a patient's genetic make-up.

The study has previously shown for every 1,000 patients treated for one year with ticagrelor instead of clopidogrel, there would be 14 fewer deaths or 11 fewer heart attacks without an increase in bleeding problems.

"The latest results on ticagrelor reinforce the positive data from the PLATO trial and suggest that ticagrelor has the potential to improve the quality of care and save many lives in the year following a heart attack, regardless of adverse effects or genetic differences in the response to clopidogrel," said Robert Storey of the University of Sheffield.

The latest findings were presented at the European Society of Cardiology (ESC) Congress 2010 and appeared in the Lancet.

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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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