(Fingolimod) for Multiple Sclerosis Multiple Sclerosis Pg 843 Silent Stroke Risk Could Rise with Hypertension Pg 844

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Positive Phase III results of in the news... Positive Phase III results of FTY720 (fingolimod) for FTY720 (fingolimod) for multiple sclerosis multiple sclerosis pg 843 Silent stroke risk could rise with hypertension pg 844

Benefits with sirolimus-eluting stents found to continue in Preliminary results from the Efficacy and all relevant end points compared with both MISSION! Intervention study pg 844 Safety of Fingolimod in Patients With placebo and a standard of care, complemented Relapsing-Remitting Multiple Sclerosis by extensive safety data.” New biodegradable polymer stent found to be ‘noninferior’ (FREEDOMS) study, a 2‑year, double-blind, The safety profile of FTY720 has been pg 845 placebo-controlled, Phase III clinical trial studied well, with more than 5300 patient- US FDA approves pitavastatin for involving 1272 relapsing–remitting multi- years of exposure, including patients now combined dyslipidemia pg 845 ple sclerosis (MS) patients in 22 countries to in their sixth year of treatment. In the assess the efficacy, safety and tolerability of FREEDOMS study, there were no cases of Recent drug approvals pg 846 oral FTY720 (fingolimod), have shown that macular edema or melanoma at the 0.5‑mg the drug could reduce the MS relapse rates dose. Reversible and generally asymptomatic by 54–60% compared with placebo, and dis- liver enzyme elevations were observed more ability progression by 30–32%. frequently with FTY720 than placebo, and Multiple sclerosis is an autoimmune dis- lung infections were also slightly more com- ease in which the immune system attacks mon. Mild elevation in blood pressure was the CNS. MS is one of the leading causes of observed with FTY720. Three patients died neurological disability in young adults. The during the FREEDOMS study, one on a new drug FTY720 is a sphingosine 1-phos- FTY720 higher dose (1.25 mg) and two on phate receptor modulator, and has the poten- placebo. None of the deaths was related to tial to be the first in this new drug class of the study drug. MS therapies. The FREEDOMS study is the second of “As an oral therapy, it is clear three Phase III studies involving more than that fingolimod potentially 4000 MS patients worldwide. Previous results represents a significant advance in from the 1‑year Trial Assessing Injectable the treatment of MS. Interferon vs FTY720 Oral in RRMS ” (TRANSFORMS) study showed a significant reduction in relapse rates compared with “The positive results from the FREEDOMS

IFN-b1a, a standard of care for MS. The third study confirm the efficacy and safety of -fin study, FREEDOMS II, is currently ongoing. golimod, and provide important evidence of its effect on disability,” said Ludwig Kappos, “The positive results from the FREEDOMS Chair of Neurology and Research Group study confirm the efficacy and safety of Leader in the Department of Biomedicine at fingolimod, and provide important the University Hospital in Basel, Switzerland, and the principal investigator of the evidence of its effect on disability. ” FREEDOMS study. “As an oral therapy, it is clear that fingolimod potentially represents a “We are proud to have reached this critical significant advance in the treatment of MS.” milestone in the development of FTY720, a Future development of FTY720 in relaps- novel oral therapy that has the potential to ing–remitting MS will focus on the 0.5‑mg transform the treatment of this ultimately dose. Regulatory submissions of the drug are disabling disease,” said Trevor Mundel, planned in the USA and EU at the end of Global Head of Development at Novartis 2009. Pharma AG (Basel, Switzerland). “FTY720 0.5-mg therapy offers compelling efficacy on Source: Novartis, Switzerland: www.novartis.com

According to a new prospective population- The group, led by Dr Sachdev, analyzed Infarcts present at both MRI scans grew based study, hypertension increases the risk findings from the 60- to 64-year-old cohort significantly over the intervening 4 years, of silent strokes, or lacunar infarct, by up of the larger prospective, longitudinal with a nonsignificant trend for correlation to 60%. PATH Through Life Study. with age. The findings from the Prince of Wales A total of 477 participants in this cohort The group added, “although this was Hospital in Sydney, Australia, have been were recruited randomly from the compul- only demonstrated in a limited number of published in Neurology, which also discusses sory electoral roll in two areas of Australia. subjects … it may indicate a progressive the prevalence of other factors such as white Among other measurements, the study process of atrophy in surrounding tissue of matter hyperintense lesions on MRI and the included two MRI brain scans carried out the lesion.” ratio of anterior ventricle to brain volume. 4 years apart. Baseline results indicated The authors concluded that “none The researchers noted that these so-called that 7.8% had at least one lacunar infarct theless, this study provides invaluable silent strokes “...are not truly silent, as they on MRI, at second MRI the prevalence rose information on the healthy population have been associated with cognitive deficits to 8.8%. in their 60s, which is the main target of and their accumulation, or presence in stra- Results indicated that those with lacu- primary prevention in vascular disease.” tegic brain regions, has also been suggested nar infarcts were significantly more likely as an important pathologic substrate of to have hypertension, as well as higher vascular dementia.” The researchers hope average systolic blood pressure and mean Source: Chen X, Wen W, Anstey KJ, Sachdev PS: that by finding a modifiable risk factor they arterial pressure. However, the degree of Prevalence, incidence, and risk factors of lacunar could gain an insight into the prevention of hypertension did not appear to impact the infarcts in a community sample. Neurology 73, cerebrovascular disease. volume of the lesions. 266–272 (2009).

Benefits with sirolimus-eluting stents found to continue in MISSION! Intervention study

Researchers from Leiden University male), who were followed for a median of benefit in STEMI patients occurred entirely Medical Center (the Netherlands) have 38 months. A total of 158 patients received within the first year”. Rates of target vessel presented the 3‑year outcomes of the SES, with 152 receiving BMS. The clini- revascularization, death and nonfatal recur- MISSION! Intervention study at the cal end points of the trial included: death, rent myocardial infarction were similar in recent European Society of Cardiology myocardial infarction, target vessel/lesion the second and third years. (ESC) Congress. They found that patients revascularization, target vessel failure However, the cumulative incidence of with ST-elevation myocardial infarction (composite of all end points related to the definite stent thrombosis was higher in the (STEMI) treated with sirolimus-eluting target vessel) and stent thrombosis. The SES group compared with the BMS group stents (SES) continued to experience bene- patients were treated with life-long aspirin (4 vs 0.7%; p = 0.11), and was statistically fits in terms of requiring significantly fewer and clopidogrel for 1 year after the stent significant for very late stent thrombosis target vessel revascularization procedures was implanted. (3.3 vs 0%; p = 0.05). compared with those treated with bare- After 3 years the researchers found that the The researchers concluded that at 3 years metal stents (BMS). However, this was at cumulative incidence of cardiac death and the SES-treated patients continued to show the cost of a higher incidence of very late myocardial infarction were similar between a trend towards a favorable clinical outcome stent thrombosis. the SES- and BMS-treated patients. There compared with the BMS-treated group. The MISSION! Intervention study was a slightly lower cumulative incidence of was a single-blind, single-center, rand- target vessel revascularization, target lesion Source: Atary JZ, Van Der Hoeven BL, Liem SS omized study to compare the use of drug- revascularization and target vessel failure et al.: Drug-eluting vs bare-metal stents for the eluting stents with BMS in the treatment in the SES group. However, this advantage treatment of ST-elevation myocardial infarction: of acute STEMI in terms of efficacy and mainly occurred within the first year of three-year clinical outcome of the MISSION- safety. The study included 310 consecu- treatment. Jael Z Atary, who presented the Intervention study. Eur. Heart J. 30(Abstract tive patients (age: 59 ± 11 years, 78% results at the ESC Congress said: “The SES Suppl.), 676 (2009).

844 Therapy (2009) 6(6) future science group Bulletin Board Bulletin Board

New biodegradable polymer stent found to be ‘noninferior’ According to the results of the Intracoronary lesion. This end point was met in 13.8% of advantages of a biodegrable polymer, this Stenting and Angiographic Results: patients treated with the biodegrable stent, report must be viewed only as an initial Test Efficacy of 3 Limus-Eluting Stents compared with 14.4% for those treated encouragement for this technology. It is (ISAR-TEST4) trial, a new type of stent with a permanent polymer stent. naive to believe that a novel technologic coated with a rapamycin-eluting biodegrad- The results were presented by Julinda breakthrough will be free of a yet to be deter- able polymer is noninferior to the two lead- Mehilli from the Technische University in mined new limitation”. Mehilli commented ing permanent polymer-based drug-eluting Munich (Germany), who said: “This study that a further 2-year analysis is planned to stent (DES) platforms. The trial represents shows the noninferiority of the biodegrad- investigate this technology further. the largest randomized study to date inves- able polymer compared with the perma- tigating the use of biodegradable polymer- nent polymer DES, but the follow-up of Source: Mehilli J: Randomized trial of 3-limus based DES. 1 year is probably too short to reveal safety agent-eluting stents with biodegradable or per- The primary end point of the trial was differences.” manent polymer coating. ISAR-TEST-4 study. a composite of cardiac death, myocar- In an accompanying editorial in the Presented at: ESC Congress 2009. 29 August–2 dial infarction related to the target vessel European Heart Journal, Aron Kugelmass September 2009, Barcelona, Spain (Prog. no.: or revascularization related to the target commented: “Despite the theoretical 1852).

US FDA approves pitavastatin for combined dyslipidemia

The US FDA has recently approved the statin market for clinically complex patient accruing many patient-years of exposure. use of Livalo® (pitavastatin) for patients populations, such as the elderly, patients Kowa Pharmaceuticals state that pitavas- with hypercholesterolemia and combined with diabetes or patients who take multiple tatin is frequently prescribed as first-line dyslipidemia. The HMG-CoA reduct- medications for comorbid conditions.” therapy for patients whose disease status ase inhibitor (statin), developed by Kowa is made more complex by concurrent ill- Pharmaceuticals (AL, USA), is expected to “Livalo has a robust safety, efficacy and nesses and medication. In the Phase III tri- be launched in the USA during spring 2010. tolerability profile, and offers an als that led to the FDA approval of Livalo, Dyslipidemia is accepted to be one of attractive alternative for patients with the statin successfully reduced low-density the principal independent predictors of lipoprotein cholesterol and improved other primary hypercholesterolemia or cardiovascular complications. Although lipid parameters in special patient popula- combined dyslipidemia. several management possibilities exist, ” tions. These included patients with diabe- mainly dietary changes, physical exercise tes, those at increased cardiovascular risk and lipid-lowering drugs, there is still a Livalo belongs to the family of statins, and the elderly. The trials demonstrated need for better control and treatment for but differs in its unique cyclopropyl group a similar safety and tolerability profile to dyslipidemia. on the base structure. The cyclopropyl other commonly prescribed statins. Kowa Pharmaceuticals America claim group is suggested to allow more effective Ben Stakely, CEO and President of Kowa that the statin will “fill an unmet need for inhibition of the HMG-CoA reductase Pharmaceuticals America, is very positive clinically complex patient populations”. enzyme, as well as greater low-density lipo- about the launch of pitavastatin in the Antonio M Gotto Jr of Cornell University protein cholesterol clearance. The drug’s USA. He states, “Kowa Pharmaceuticals (NY, USA) comments, “Livalo has a robust property of only being minimally metabo- America is very pleased with the approval safety, efficacy and tolerability profile, and lized through the cytochrome P4590 path- of Livalo and is excited about the oppor- offers an attractive alternative for patients way by the liver makes it ideal for patients tunity to introduce this new therapeutic with primary hypercholesterolemia or com- who take other medications. option to physicians and patients.” bined dyslipidemia.” He continues, “Livalo Livalo is only just being launched in has very positive attributes that will help the USA, but is already being used in Source: www.kowapharma.com/PressReleases/ continue to fill current unmet needs in the Japan, South Korea, Thailand and China, news080209.htm

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Inc.

Novartis Ipsen Centocor Ortho Biotech Basilea Pharmaceutica MediGene & Co Merck Paladin Labs Aurobindo Pharma Generex Eurand Pharmaceuticals Bristol-Myers- Squibb Company and AstraZeneca Mutual Pharmaceutical Company Manufacturer USA Spain USA Switzerland Germany EU Canada Switzerland USA USA EU USA Region insulin

For the treatment of high blood pressure in patients not adequately of high blood pressure For the treatment blocker monotherapy, or angiotensin receptor on aliskiren controlled and as initial therapy in patients likely to need multiple drugs achieve goals their blood pressure in the appearance of moderate to For the temporary improvement (vertical lines between the glabellar lines seen at the frown severe when in adult men and women aged 65 years under, eyebrows), the severity of these lines has an important psychological impact on patient to potent hand eczema unresponsive chronic For adults with severe topical corticosteroids of genital warts For the treatment 2 diabetes Type hypoglycemia in diabetic patients being of severe For the treatment with treated in adults glycemic control to improve An adjunct to diet and exercise 2 diabetes mellitus. with Type and children For adult patients 18 years or older with moderate-to-severe plaque For adult patients 18 years or older with moderate-to-severe candidates for phototherapy or systemic therapy psoriasis who are Patients with serious or life-threatening Type 1 or 2 diabetes who have Type Patients with serious or life-threatening no satisfactory alternative therapy options for the condition, and who ongoing Phase III trial not eligible to participate in the company’s are for the drug Exocrine pancreatic insufficiency due to cystic fibrosis or other insufficiency due to cystic fibrosis Exocrine pancreatic conditions For adult patients with Type 2 diabetes mellitus to improve glycemic 2 diabetes mellitus to improve For adult patients with Type control To reduce triglyceride levels in patients with severe hypertriglyceridemia triglyceride levels in patients with severe reduce To low-density- of total cholesterol, (> 500 mg/dl) and for the reduction B and to triglyceride and apolipoprotein cholesterol, lipoprotein in patients with primary cholesterol high-density lipoprotein increase hyperlipidemia or mixed dyslipidemia Indication for

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Stelara™ Toctino Glucophage Oral-lyn™ Zenpep™ Onglyza™ Glucagen Fibricor™ Valturna Endocrinology & metabolism Dermatology Cardiology Drug approvals August to October 2009. name Trade

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Meda Pharmaceuticals Novartis Wilmington Pharmaceuticals Daiichi Sankyo Merck Sharp & Merck Dohme Roche GlaxoSmithKline Theravance Sanofi Pasteur Abbott Laboratories UCB PharmaUCB Manufacturer EU USA USA USA USA EU USA USA USA USA EU Region For the symptoms of seasonal and perennial allergic rhinitis For the symptoms of seasonal and perennial of symptoms aged 6 months and older for the relief For children hives) idiopathic urticaria (chronic allergic rhinitis and chronic perennial aged 2 years and older for symptoms of seasonal and for children allergic rhinitis An add-on therapy for severe persistent allergic asthma in children aged persistent allergic asthma in children An add-on therapy for severe 6–11 years For relieving symptoms in adults with acute and recurrent diabetic symptoms in adults with acute and recurrent For relieving and for short-term therapy (4–12 weeks) in adults with gastroparesis disease that fails to reflux symptomatic, documented gastroesophageal to conventional therapy respond An adjunct to diet and exercise for the reduction of elevated for the reduction An adjunct to diet and exercise girls, in boys and postmenarchal cholesterol low-density lipoprotein familial hypercholesterolemia 10–17 years of age, with heterozygous alone or in combination with a statin after failing an adequate trial of diet therapy For use in combination with other antiretroviral medicinal products medicinal products For use in combination with other antiretroviral infection in adult patients, including of HIV-1 for the treatment as therapy for the first time (treatment-naïve), patients starting HIV-1 adult patients. well as treatment-experienced Prevention of cytomegalovirus disease in pediatric kidney and heart Prevention transplant patients ≥ 4 months of age at high risk developing cytomegalovirus For children aged 15 months through 4 years to prevent invasive 4 years to prevent aged 15 months through For children disease caused by Haemophilus influenzae type B For the treatment of complicated skin and skin-structure infections of complicated skin and skin-structure For the treatment caused by susceptible Gram-positive bacteria For active immunization of persons 6 months age and older against influenza disease caused by pandemic (H1N1) 2009 virus For once-daily as well as twice-daily use in treatment-naïve patients in For once-daily as well twice-daily use in treatment-naïve agents combination with other antiretroviral Indication Azelastine HCl Levocetirizine dihydrochloride Omalizumab Metoclopramide hydrochloride Colesevelam hydrochloride Generic name Raltegravir Valganciclovir hydrochloride Valganciclovir Telavancin Lopinavir/ritonavir

® ® ® ® Xolair Xyzal Hiberix vaccine Metozolv™ ODT Welchol™ Astepro Vibativ™ Influenza A (H1N1) 2009 monovalent vaccine Kaletra™ Valcyte Isentress Infectious disease Gastroenterology & hepatology Immunology Drug approvals August to October 2009 (cont.). name Trade

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Novartis Shire Lundbeck Schering-Plough AstraZeneca Spectrum Roche Wyeth Europa AstraZeneca Allos Therapeutics Roche BioAlliance Pharma Lumavita Theravance Covidien King Manufacturer USA USA USA USA EU USA EU EU EU USA UK Switzerland Switzerland Canada USA USA Region vaginitis

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Guanfacine Interferon b -1b Interferon Vigabatrin Asenapine Quetiapine Ibritumomab Rituximab Temsirolimus Pralatrexate injection Pralatrexate Quetiapine tablets extended-release Rituximab Morphine/naltrexone Generic name Miconazole Pentamycin Telavancin

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Ortho

Enzon Pharmaceuticals/ UCB Centocor Biotech and Ista Pharmaceuticals Schering-Plough Sirion Therapeutics CSL Behring Bayer HealthCare Genzyme Anika Therapeutics BioSpecifics Technologies CSL Behring Manufacturer EU EU USA USA USA USA USA USA USA USA Region For the the For

methotrexate, for the treatment of of treatment the for methotrexate,

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moderate-to-severe, active rheumatoid arthritis in adult patients when when patients adult in arthritis rheumatoid active moderate-to-severe, including therapy, drug anti-rheumatic disease-modifying to response the combination in or alone use for Also inadequate. been has methotrexate, with For the treatment of adult patients with moderately to severely active of adult patients with moderately to severely For the treatment rheumatoid arthritis disease- previous to response the when patients adult in arthritis inadequate. been has therapy drug anti-rheumatic modifying who patients adult in spondylitis ankylosing active severe, of treatment therapy conventional to inadequately responded have For ocular itching associated with allergic conjunctivitis in patients 2 angioedema, which can For adults and adolescents with hereditary surgery or infection in patients occur spontaneously or during stress, angioedema diagnosed with hereditary of heavy menstrual bleeding in women who choose For the treatment to use intrauterine contraception as their method of kidney of serum phosphorus in patients with chronic For the control disease on dialysis For use in combination with combination in use For Acute herpetic keratitis For the treatment of osteoarthritis the knee For the treatment For the treatment of Dupuytren’s disease of Dupuytren’s For the treatment For routine prophylaxis in children with hemophilia A who are 16 years with hemophilia A who are in children prophylaxis For routine joint damage old or younger and do not have pre-existing Indication Certolizumab pegol Bepotastine besilate ophthalmic solution C1-esterase inhibitor Levonorgestrel-releasing intrauterine system Sevelamer carbonate Golimumab Ganciclovir ophthalmic gel 0.15% Sodium hyaluronate Collagenase clostridium histolyticum Antihemophilic factor (recombinant) Generic name FS ® ® ® ® ® Bepreve™ Berinert Simponi™ Zirgan™ Helixate Renvela Monovisc™ Xiaflex™ Cimzia Mirena Opthalmology Other Rheumatology Drug approvals August to October 2009 (cont.). name Trade

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