Primary Pulmonary Hypertension News - Menu Male sex drug is being used to keep mum Catherine alive Doctors welcome results with woman who had three years to live Dave Mark Now Mrs Lee, 32, is looking forward to many happy years with her two-year-old daughter Poppy. She takes enough of the impotence drug to fuel 10 men on a daily basis. She said: "Before I started taking the Cialis I was mainly sedentary. "Rather than being scared when I was diagnosed, I was actually relieved. I was pleased to know what was wrong with me, and I just thought 'It's the 21st century, there must be something that can be done', but I didn't think Viagra would be the drug to help me." Mrs Lee, who used to be a switchboard operator before the one-in-a-million disease struck her down, was first diagnosed with the progressive heart and lung condition about a year ago. Doctors initially diagnosed anxiety and she was put on Prozac for three years. It was not until she gave birth to her daughter prematurely, at 27 weeks, that her condition worsened. Simple day-to-day tasks began causing her to lose breath and everything become a struggle. Looking after her daughter was exhausting and she would often black out from the intensity of the palpitations. Mrs Lee, who is married to 33-year-old joiner Matthew, was eventually sent to a neurologist. He referred her to a cardiologist and her condition, which results in the progressive narrowing of the blood vessels of the lungs, was finally diagnosed. She was then referred to Professor Alyn Morice, from Castle Hill Hospital in Cottingham who is a world expert and is conducting research to see if the drug can prolong the lives of people with PPH. Prof Morice, who is a professor of respiratory medicine, said: "I am the only person in the world prescribing this drug for PPH and so far, over the last 18 months or so, we have had tremendous results. PPH was a condition that was almost 100 per cent fatal 20 years ago and now I have lost only one patient in the last five years. "The drug works in the same way as Viagra. The only difference is that Cialis has a much longer-lasting effect. It works by relaxing the blood vessels, which enables blood to flow through the penis and create an erection. But in Catherine's case, it helps relax arteries in her lungs, allowing blood to be pumped through." The only set-back is that Mrs Lee is developing a tolerance to the medication and she has to keep increasing her doses. Arena shares gain from results of weight-loss drug APD356 By Penni Crabtree Based on the promising Phase 2 study results, the San Diego biotechnology company said it plans to launch a final, Phase 3 human study of the drug, known as APD356, about the middle of next year. Obese volunteers who took Arena's drug over three months lost an average of 7.9 pounds at the highest 20-milligram dose. Those who took the drug at two lower doses lost an average of 5.7 pounds and 4 pounds respectively. The 469 people who participated in the study were not encouraged to exercise or diet. Wall Street analysts were particularly pleased that the therapy showed no evidence of causing the kind of dangerous cardiovascular side effects that led to the withdrawal of Wyeth's once-popular fen-phen diet drug. APD356 targets a single brain receptor that regulates metabolism and controls appetite, similar to the receptor that Wyeth's fen-phen diet drug targeted. Unlike fen-phen, Arena's drug doesn't release hormones or target additional receptors affecting the brain and heart, according to Arena. The most common side effect of Arena's drug was headache. Cory Kasimov, an analyst at Oppenheimer & Co., said Arena's drug exceeded expectations. "If they're able to replicate this kind of data in a Phase 3 study, we're talking about a potential blockbuster drug," said Kasimov, who rates Arena a "buy" and doesn't own any shares. If the Arena drug proves successful in longer Phase 3 studies, it could be on the market in 2009. Demand for obesity drugs is robust. There are more than 1 billion overweight adults in the world, and at least 300 million of them are obese, according to the World Health Organization. Obesity-related health problems consume as much as 7 percent of health care dollars, and obesity is linked to such diseases as diabetes and cancer. About 30 percent of U.S. adults over age 20, or about 60 million people, are obese, according to the National Center for Health Statistics. If approved, Arena's drug would face competition from existing medicines such as Roche's Xenical and Abbott Laboratories' Meridia, both of which have side-effect issues. Meridia, for instances, can cause high blood pressure. Another diet drug, Sanofi-Aventis' experimental diet drug Acomplia, has been submitted to the U.S. Food and Drug Administration for approval. That drug blocks food cravings, targeting an area of the brain that makes people hungry when they smoke marijuana. Jack Lief, Arena's chief executive, said yesterday that his company's diet drug performed as well or better than the rival diet drugs. Arena will likely find a pharmaceutical company partner to help develop the medicine and market it if it wins regulatory approval, he said. "Every biotech company experiences storms, but that way you appreciate the good stuff," said Lief, whose company employs 300. "And this is great, it doesn't get much better than this." Arena also has a handful of other experimental drugs in development, including a sleeping pill that is about to enter Phase 2 studies, a diabetes treatment in partnership with with Johnson & Johnson, and an atherosclerosis drug with Merck & Co. The biotech had $148 million in cash and investments at the end of September. Positive top-line results from a Phase 2 clinical trial of APD356 demonstrated a highly statistically significant weight loss Our most advanced product candidate is APD356, a novel and selective 5-HT2C receptor agonist for obesity currently in a Phase 2b clinical trial. Obesity affects tens of millions of adults and children in the United States and poses a serious long-term threat to their health and welfare. Medical treatment options for obesity and metabolic syndrome are currently very limited. Based on the clinical and pre-clinical evidence to date, we believe that APD356 has the potential to help patients reduce their weight in an effective, safe and controlled manner. Because our data indicate that APD356 appears to stimulate the 5-HT2C serotonin receptor more selectively than fenfluramine and dexfenfluramine, we believe that APD356 is less likely to cause the cardiovascular side effects associated with those compounds. Until 1997, Wyeth marketed fenfluramine and dexfenfluramine, serotonin-releasing agents and non-selective serotonin receptor agonists, which were often used in combination with phentermine for the treatment of obesity. The combination of fenfluramine or dexfenfluramine with phentermine is commonly referred to as fen-phen. Despite their efficacy as appetite suppressants, both fenfluramine and dexfenfluramine were withdrawn from the market in 1997 after reported incidences of heart valve disease and pulmonary hypertension associated with their usage. Clinical Development Over the 28 day treatment period of the trial, there was a highly statistically significant (p=.0002) average weight loss of 2.9 pounds in patients taking the 15 mg dose of APD356 versus 0.7 pounds for the placebo group. The table below summarizes the top-line mean weight change for all patients completing the study in each group. Group Mean Weight Change APD356 was generally well tolerated at all doses investigated, and there were no serious adverse events in the trial. Events that occurred in 5% or more of patients in a treatment group are listed below:
Phase 1 In November 2004, we announced results from a Phase 1b clinical safety trial of APD356 in obese volunteers. In this trial, 27 subjects (15 males and 12 females) with an average body mass index, or BMI, of 31, and a BMI range of 25 to 58, were enrolled. Participants were administered 3 mg, 10 mg and 20 mg doses of APD356 or placebo daily for 14 days in successive cohorts of nine subjects (six received APD356 and three received placebo) and remained within a Phase 1 unit throughout the dosing period. Participants were instructed to maintain their usual exercise patterns, and were offered sufficient food to maintain their desired intake levels. APD356 was well tolerated; there were no severe or serious adverse events reported, no withdrawals due to an adverse event, and no reports of euphoria, dysphoria, or disorientation. The most common side effects, occurring primarily at the 20 mg dosage level, were headache and nausea, sometimes with vomiting. These side effects were occasional and generally mild in nature. APD356 continued to demonstrate very predictable pharmacokinetic behavior, similar to that found in its Phase 1a trial. The maximum plasma concentration and exposures increased in proportion with increasing doses of APD356, and there were no apparent gender differences in pharmacokinetic parameters. Based on a comparison of echocardiograms taken at screening with those taken at the end of treatment and two and three months thereafter, there was no apparent drug effect on heart valves or pulmonary artery pressure. This Phase 1b study was neither designed nor powered to detect significant weight change between treatment groups. When compared with placebo, none of the mean changes in weight in the groups that received APD356 were statistically significant. Mechanism and Preclinical Development In a free-fed rat model, APD356 reduced total food intake in a dose-dependent manner. APD356 dosed once, orally at 6 mg/kg, 12 mg/kg and 24 mg/kg reduced food intake approximately 12% to 25% over 22 hours compared to a saline control. In the same model, dexfenfluramine dosed once, orally at 0.3 mg/kg, 1 mg/kg, and 3 mg/kg reduced food intake approximately 10% to 30% over the same time period. In an obese rat model, APD356 caused dose-dependent reductions in body weight after 14 days of oral administration. APD356 dosed at 4.5 mg/kg, 9 mg/kg, 18 mg/kg twice-daily, and 36 mg/kg once-daily reduced bodyweight by approximately 3%, 6%, 11%, and 12%, respectively. The reductions in bodyweight caused by APD356 appear to be due to lowered body fat, as lean body mass in the obese rats was unaffected at all APD356 doses. Our product candidates have not been approved by the U.S. Food and Drug Administration or any international regulatory agency. |