Volume: 05

Drug Information Centre (DIC) Indian Pharmaceutical Association, Bengal Branch Tele fax: 033 24612776, E-mail: ipabengal.dic@gmail.com Web Site: http://www.ipabengal.org Contact: 09830136291

Drug Information Bulletin (Electronic)

th

Year

Number: 24

25th September 2011

New Drug: Fampridine Health Min constitutes 12 new drug advisory committees to help DCGI on new drugs, clinical trial applications EMA recommends removing Lacosamide Syrup from market FDA approves Strides Arcolab's Vancomycin Hydrochloride Injection Online Map shows patterns of Antibiotic-Resistant Bacteria Merck tells staff of layoffs by end of October New Malaria Vaccine study seeks healthy volunteers Forthcoming Event

Content

New Drug: Fampridine Fampyra (Biogen) 10 mg modified release tablets Approved indication: multiple sclerosis Australian Medicines Handbook section 16.6 Fampridine is a potassium channel blocker indicated for symptomatic improvement of walking in adults with multiple sclerosis, including relapsing remitting, secondary progressive, progressive relapsing and primary progressive. Currently there are no other drugs for this indication. Fampridine is thought to increase conduction in demyelinated nerves by inhibiting potassium channels. It can be used on its own or with other treatments for multiple sclerosis, including immunomodulatory drugs. The efficacy of fampridine has been studied in two phase III trials.1,2 In the first trial, 301 patients with walking

difficulties associated with multiple sclerosis were randomised to fampridine 10 mg twice daily or placebo, for 14 weeks. The primary outcome was based on changes in walking speed over 25 feet (7.6 m). A responder was defined as someone who consistently walked faster during treatment compared to baseline. In the fampridine group, 35% (78/224) of patients responded compared to only 8% (6/72) in the placebo group. The average increase in walking speed of people who responded to fampridine was 0.51 feet/second (approximately 15.5 cm/second) (25% faster).1 These results were confirmed in a second similarly designed trial in which 43% (51/119) of patients responded to fampridine compared to only 9% (11/118) of patients to the placebo. On average, patients who responded to fampridine walked 24.7% faster.2 Urinary tract infection was a very common adverse event with ampridine.

2 Neurological effects were common and included insomnia, balance disorder, dizziness, headache and asthenia. Falls and severe anxiety were also reported. In a trial of 206 patients, serious events were more common at higher doses (4% with placebo, 0% with 10 mg, 8% with 15 mg and 12% with 20 mg fampridine). One patient discontinued the 15 mg dose of fampridine because of nausea and dizziness and five patients discontinued the 20 mg dose two patients had seizures, one developed abnormal coordination, one had chest discomfort and headache and one patient had blurred vision, chest discomfort, balance disorder, headache and paraesthesia.3 Seizures have also occurred postmarketing and fampridine is contraindicated in patients with a history of seizures. Because of this potential toxicity, patients should not take a double or extra dose when a dose is missed. Tablets should be taken whole and not crushed or chewed. Following oral administration, peak concentrations of fampridine are reached after 34 hours. It is primarily excreted unchanged in the urine. The elimination half-life is normally 5.26.5 hours, but is prolonged in patients with renal impairment. Fampridine is therefore contraindicated in moderate to severe renal impairment. If renal function has not been assessed, creatinine clearance should be estimated before starting treatment. This is particularly important in the elderly. In patients with mild impairment, monitoring of renal function should be considered. This drug has not been tested in pregnant and lactating women. As fampridine is lipophilic, it may be excreted in human milk. Fampridine is the first drug to help improve walking in patients with multiple sclerosis. However in the trials, less than half of the patients (3543%) consistently walked faster (increase of 15.5 cm/second) after taking fampridine. Doctors and their patients have to consider whether this potential benefit is worth the risk of seizures and other serious neurological adverse effects. The safety and efficacy of fampridine during an exacerbation of multiple sclerosis is not known as these patients were excluded from the trials. Fampridine should only be continued if the patient responds within eight weeks of treatment. References * 1. Goodman AD, Brown TR, Krupp LB, Schapiro RT, Schwid SR, Cohen R, et al. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet 2009;373:732-8. 2. Goodman AD, Brown TR, Edwards KR, Krupp LB, Schapiro RT, Cohen R, et al. A phase 3 trial of extended release oral dalfampridine in multiple sclerosis. Ann Neurol 2010;68:494-502. 3. Goodman AD, Brown TR, Cohen JA, Krupp LB, Schapiro R, Schwid SR, et al. Dose comparison trial of sustainedrelease fampridine in multiple sclerosis. Neurology 2008;71:1134-41.
Source: Aust Prescr 2011;34:119-123

Health Min constitutes 12 new drug advisory committees to help DCGI on new drugs, clinical trial applications The Union health ministry has formed 12 New Drug Advisory Committees (NDAC), comprising experts in the respective fields, to advise the Drugs Controller General of India (DCGI) in matters for review of applications of new drugs and clinical trials. Each of the panels set up to advise in matters related to review and regulatory approval of clinical trials and new drugs, except for Investigational New Drugs (INDs), relating to different therapeutic areas, has ten members. The panels were

3 formed on reproductive and urology, cardiovascular and renal, ophthalmology, vaccines, dermatology and allergy, anaesthetics and rheumatology, neurology and psychiatry, pulmonary, oncology and haematology, gastroenterology and hepatology, metabolism and endocrinology, and antimicrobialantiparasitic-antifungal-antiviral areas. "The committee will advise DCGI in matters to undertake in-depth evaluation of non-clinical data including pharmacological toxicological data, clinical trial data (phase I, II, III, and IV) furnished by the applicant for approval of new drug substances of chemical and biological origin to be introduced first time in the country including vaccines and rDNA derived products," according to an official note by the health ministry. The panels will also evaluate data being submitted by the applicants on global clinical trials, fixed dose combinations of two or more drugs to be introduced for the first time in the country. It will help preparing guidelines for clinical research industry in evolving acceptance criteria for marketing approval of new drugs of different therapeutic categories. The panel will also define roadmap for research industry for appropriate development of new drugs relevant to Indian population. "While considering cases of new drugs, the committee will examine essentiality and desirability of new drugs in terms of assessment of risk versus benefit to the patient, innovation vis--vis existing therapeutic option and unmet medical need in India," the note said. Application for new drugs and global clinical trials will be evaluated by the committee either through meetings or by circulation of the applications. The term of the committees is for three years. Office of the DCGI will initially examine the applications and if any data is lacking the same will be informed to the applicant within 45 working days or else the data will be forwarded to the members of the committee in the respective areas. EMA recommends removing Lacosamide Syrup from market The Wall Street Journal /Dow Jones Newswires reports that the European Medicines Agency yesterday issued a recommendation by its Committee for Medicinal Products for Human Use that Vimpat (lacosamide) 15 mg/ml syrup should no longer be marketed. The reason given for the recommendation is that the syrup did not have an even distribution of lacosamide so that the amount patients received could not be guaranteed. FDA approves Strides Arcolab's Vancomycin Hydrochloride Injection Bloomberg News reports, "Strides Arcolab Ltd. (STR), an Indian drugmaker, received approval from the US Food and Drug Administration for its vancomycin hydrochloride injection, an antibiotic used to fight serious bacterial infections." Online Map shows patterns Antibiotic-Resistant Bacteria of

The Washington Post reports in its "The Checkup" blog on "the 'ResistanceMap'... by 'Extending the Cure,' a research project that studies the rising problems of antibiotic resistance based at the Center for Disease Dynamics, Economics & Policy." The map is based on data from "the federal Centers for Disease Control and Prevention, the Food and Drug Administration, the European Antimicrobial Resistance Surveillance Network and the Canadian Antimicrobial Resistance Alliance." Extending the Cure director Ramanan Laxminarayan said in launching

4 the map, "With this tool, public health officials, researchers and others can see the progression of antibiotic resistance in the United States and worldwide." The map shows "that Western Europe is doing a better job than the United States of controlling certain resistant microbes," while in the US, "the South has higher rates of resistance compared to the West or Northeast." Merck tells staff of layoffs by end of October Merck & Co. will lay off personnel by the end of October, according to a company email to staff, as the pharmaceutical giant continues cutting its workforce. The company, with about 12,000 workers in the Philadelphia area, said July 29 that it planned to cut 12 percent to 13 percent of its workforce of about 100,000 by 2015 as it adjusts to market conditions and its 2009 acquisition of Schering Plough. "Merck is facing enormous challenges," U.S. Market president Mark Timney said in an e-mail Thursday to staff that was obtained by The Inquirer. "The external environment is tougher than ever, with an unprecedented pace of change that continues to accelerate." Company officials confirmed that Timney's e-mail was authentic but declined any other comment. "In the coming weeks, we will restructure the following select HQ functions and field groups within the U.S. Market: Marketing & Customer Solutions; Managed Markets & Policy; Strategy & Commercial Model Innovation; and the Neuropsychiatric and Women's Healthcare specialty sales teams," Timney's e-mail said. Merck eliminated jobs before and after its acquisition of Schering Plough. Merck's headquarters is in Whitehouse Station, N.J., but the company has several facilities elsewhere in New Jersey and a large operation in West Point, Montgomery County. Pharma-industry watchers have suggested that about 5,200 of the total cuts could be U.S. jobs, with from 3,000 to 4,000 in New Jersey and Pennsylvania. A Merck spokesman would not comment on the state-by-state plans. The cuts through October won't be the end of the process, though. In August, Merck offered buyout packages to some employees, but there was no expectation that the buyouts alone would meet the numbers required by management. Merck said that in some areas it would continue to add employees but cut elsewhere. New Malaria Vaccine study seeks healthy volunteers Malaria poses an enormous global health burden. According to the World Health Organization, approximately 3.3 billion people half of the worlds population are at risk of contracting the disease. The NIAID Vaccine Research Center (VRC) has launched a new clinical study that will evaluate a vaccine designed to prevent malaria. The study will assess the safety and tolerability of the vaccine at different doses, as well as its ability to generate an immune response. Healthy volunteers ages 18 to 45 years old are needed to participate in the study, which is being conducted at the NIH Clinical Center in Bethesda, MD. Financial compensation for study participation will be provided. Forthcoming Event: The Third International Conference for Improving Use of Medicines (ICIUM2011) Antalya, Turkey November 14-18, 2011