Medicare Part D Open Enrollment Ends Tomorrow (December 31, 2010)

The open enrollment season for Medicare Part D runs from November 15 through December 31. During this period newly eligible beneficiaries can choose a new drug plan and existing beneficiaries can review their current prescription drug plan to ensure that it best fits their needs.
To help beneficiaries navigate through the details of different drug plans, the Centers for Medicare and Medicaid recently updated its Plan Finder tool. Visit Medicare.gov to use the Plan Finder tool.

FDA Approves Impax Doryx(R) 75 And 100MG Generic Antibiotic Tablets

Impax Laboratories Inc announced that it had received the Food and Drug Administration's approval for the company's Generic Version of the Antibiotic drug, Doryx(R) in 75 and 100mg dosages.
The drug is used for treating rickettsial infections, sexually transmitted infections, respiratory tract infections, specific bacterial infections, ophthalmic infections, anthrax, including inhalational anthrax (post-exposure), alternative treatment for selected infections when penicillin is contraindicated, adjunctive therapy in acute intestinal amebiasis and severe acne, and prophylaxis of malaria.
There is an ongoing patent infringement lawsuit filed by Warner Chilcott Limited and Mayne Pharma International Pty. Ltd.on the Impax's generic version of the drug.
Following is the Press release by Impax

Impax Laboratories Receives Final FDA Approval for Generic Doryx(R) 75 and 100mg Tablets
HAYWARD, Calif., Dec 29, 2010 (BUSINESS WIRE) -- Impax Laboratories, Inc. (NASDAQ: IPXL) today announced that the U.S. Food and Drug Administration (FDA) has granted final approval of the Company's Abbreviated New Drug Application for the generic version of Doryx(R) (doxycyline hyclate delayed-release) 75 and 100mg tablets. The Company is preparing for product launch through Global Pharmaceuticals, Impax's generic division.

In December 2008, Warner Chilcott Limited and Mayne Pharma International Pty. Ltd. filed suit against the Company in the U.S. District Court for the District of New Jersey, alleging patent infringement for the filing of the Company's ANDA. Litigation is ongoing.

Doryx(R) is a tetracycline-class antibacterial indicated for rickettsial infections, sexually transmitted infections, respiratory tract infections, specific bacterial infections, ophthalmic infections, anthrax, including inhalational anthrax (post-exposure), alternative treatment for selected infections when penicillin is contraindicated, adjunctive therapy in acute intestinal amebiasis and severe acne, and prophylaxis of malaria. According to Wolters Kluwer Health, U.S. sales of Doryx(R) 75 and 100 mg were approximately $25 million in the 12 months ended October 2010.

Tiotropium Bromide Aids In Treating Uncontrolled Asthma In Adults.

Long-acting beta-agonist (LABA) therapy improves symptoms in patients whose asthma is poorly controlled by an inhaled glucocorticoid alone. Alternative treatments for adults with uncontrolled asthma are needed.

In a test involving a three-way, double-blind, triple-dummy crossover trial covering 210 patients with asthma, The team evaluated the addition of tiotropium bromide (a long-acting anticholinergic agent approved for the treatment of chronic obstructive pulmonary disease but not asthma) to an inhaled glucocorticoid, as compared with a doubling of the dose of the inhaled glucocorticoid (primary superiority comparison) or the addition of the LABA salmeterol (secondary noninferiority comparison). 

The use of tiotropium resulted in a superior primary outcome, as compared with a doubling of the dose of an inhaled glucocorticoid, as assessed by measuring the morning peak expiratory flow (PEF), with a mean difference of 25.8 liters per minute (P<0.001) and superiority in most secondary outcomes, including evening PEF, with a difference of 35.3 liters per minute (P<0.001); the proportion of asthma-control days, with a difference of 0.079 (P=0.01); the forced expiratory volume in 1 second (FEV1) before bronchodilation, with a difference of 0.10 liters (P=0.004); and daily symptom scores, with a difference of -0.11 points (P<0.001). The addition of tiotropium was also noninferior to the addition of salmeterol for all assessed outcomes and increased the prebronchodilator FEV1 more than did salmeterol, with a difference of 0.11 liters (P=0.003).

When added to an inhaled glucocorticoid, tiotropium improved symptoms and lung function in patients with inadequately controlled asthma. Its effects appeared to be equivalent to those with the addition of salmeterol. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00565266.).

NEJM via Pubmed

mHealth, Mobile Health Apps Gets A Search Engine From Mimvi

SAN FRANCISCO, Dec. 2, 2010 (GLOBE NEWSWIRE) -- Mimvi, Inc. (OTCBB:MIMV - News), the world's largest pure-play search, discovery and recommendation engine for finding mobile apps (or applications), has announced the launch of a specialized search and discovery engine for health-related mobile apps. The site, which is located at http://www.mimvi.com/health, provides a unique platform for companies and consumers worldwide. It is available for license to any health-related organization and other strategic partners.
Industry experts are forecasting a revolution in health-related mobile apps. A recent study by the research2guidance group predicts that the mobile healthcare market will grow exponentially to reach over 500 million mobile users, or 30 percent of an estimated 1.4 billion smartphone subscribers worldwide by 2015. Bill Gates recently validated this opportunity at the mHealth Summit, a conference for companies involved in mobile technology and health. Mr. Gates was quoted as saying, "Diagnosis of malaria and TB will likely be the first ones you can assign a number to and say without this mobile phone app these people would have died."
Kasian Franks, Mimvi's Founder and CEO, reinforced these insights, "The benefits that mobile technologies and, specifically, apps bring to healthcare are tremendous. This "megatrend" will be driven by both healthcare professionals and consumers alike. The developments we have seen to date, encompassing everything from diabetes and cholesterol management to finding the nearest ER, merely represent the tip of the iceberg. In the future, we will see all kinds of health and wellness-related applications that will save millions of lives and millions of dollars--monies which can be funneled into future research and development, as opposed to feeding a bureaucratic machine." Franks continued, "The technology that lives inside mobile devices provides so many opportunities for future innovation in the healthcare world. Think about the possibilities that cameras, environmental sensors and GPS technologies can create in saving lives and helping people proactively manage their health."
Mimvi's proprietary search and recommendation engines provide more results with greater relevance across multiple platforms than any other player in the world today--a competitive advantage that Franks went on to emphasize in the context of health, "Mimvi Health is the only specialized search and recommendation engine for healthcare in the world today. This puts us in a unique position to maximize the business opportunities for all key stakeholders: advertisers, healthcare providers and developers. This sales funnel is further widened by our proprietary Amazon-like recommendation system which provides truly meaningful suggestions--a critical component in our value proposition and the mobile apps market as a whole."
The revenue opportunities in the mobile industry are significant. A new report from BIA/Kelsey shows that U.S. mobile advertising revenues will grow from $491 million in 2009 to $2.9 billion in 2014. Mr. Franks spoke further about Mimvi's revenue model, "Our revenue strategy will include different approaches, from proven revenue models such as sponsored search results to proprietary revenue --generating technologies we are developing which will facilitate financial transactions inside the apps themselves. We will share more on this front in due course."

Schizophrenia (RG1678), Multiple Sclerosis (Ocrelizumab) Drugs By Roche Enter Phase III Of Clinical Trials.I

Roche Holding AG (ROG.VX) Thursday announced that drugs slated to treat diseases like schizophrenia, and multiple sclerosis will enter phase III of clinical trails and may submit applications for as many as 10 new drugs by the end of 2013. Roche is the world's biggest cancer drug maker and is seeking new paths outside the oncology arena to mitigate the effects of recent development setbacks. Avastin, the company’s top seller, failed in studies in prostate, stomach and early colorectal cancer.

Start of phase III programs for potential breakthrough therapies in schizophrenia and multiple sclerosis

Schizophrenia

Positive phase II proof-of-concept data with RG1678 in patients with predominantly negative symptoms of schizophrenia were recently presented at an international medical meeting³. Based on these promising results, a global phase III program has been initiated which includes a total of six studies investigating RG1678 in combination with standard of care antipsychotic drugs in patients with either negative symptoms⁴ or residual positive symptoms of schizophrenia⁵. Running the studies for both indications in parallel will allow a better understanding of the effect of RG1678 on a broad spectrum of symptoms and its value in the management of patients at different phases of their disease. The first patient was randomized into the phase III program in November 2010.

RG1678 is an investigational first-in-class glycine reuptake inhibitor that normalizes glutamate neurotransmission, thereby targeting an important pathway in the treatment of psychiatric disorders. By normalising glutamate neurotransmission in the brain, RG1678’s unique mode of action could also have valuable therapeutic applications in other psychiatric indications beyond schizophrenia.

Multiple sclerosis

Ocrelizumab, a humanized anti-CD20 antibody administered as a six-monthly infusion, demonstrated a highly significant reduction in disease activity as measured by brain lesions (96% for 2000mg and 89% for 600mg ocrelizumab dosing regimens) and relapse rate (73% for 2000mg and 80% for 600mg ocrelizumab at week 24) compared to placebo in a phase II study in relapsing-remitting multiple sclerosis (RRMS). The efficacy data, amongst the highest seen in a phase II RRMS study, were recently reported at the ECTRIMS conference. Based on these results, ocrelizumab will move into phase III studies in multiple sclerosis. Two studies will explore ocrelizumab’s efficacy in RRMS head-to-head versus interferon, the current standard of care, and one study will investigate the potential of ocrelizumab in patients with primary-progressive multiple sclerosis (PPMS).  Phase III studies for ocrelizumab will commence in the first quarter of 2011.

 Press Release by Roche

Clobazam Found To Be Positive In Adjunctive Treatment of Seizures Associated With Lennox-Gastaut Syndrome

Lundbeck A/S announced today at the 64th annual meeting of the American Epilepsy Society in San Antonio, Texas, that the study of clobazam as adjunctive therapy in treating seizures associated with Lennox-Gastaut syndrome (LGS) to be positive.Two highest dosages of clobazam as add-on therapy achieved the primary endpoint with a statistically significant reduction in average weekly rate of drop seizures, compared with placebo.. 77.6 percent of patients who received high-dosage clobazam achieved a 50 percent or greater reduction in average weekly rate of drop seizures. Lundbeck anticipates NDA submission by year-end after which the agency's confirmation of receipt of the submission will be awaited. ClinicalTrials.gov also lists this as the Phase III study of the Clobazam's effectiveness.

H. Lundbeck A/S (Lundbeck) today presented positive data from its pivotal phase III study to determine the efficacy and safety profiles of the investigational compound clobazam as adjunctive therapy in treating seizures associated with Lennox-Gastaut syndrome (LGS). In the study, clobazam met its primary efficacy endpoint and was further supported by several key secondary efficacy endpoints.1 LGS is a rare and severe form of epilepsy that is typically diagnosed in childhood and persists into adulthood.2,3 Results from this largest clinical trial to date in LGS patients were presented at the 64th annual meeting of the American Epilepsy Society in San Antonio, Texas (Poster No. 1.283).1,4
This prospective, double-blind, placebo controlled study randomized 238 patients diagnosed with LGS to one of three different dosages of clobazam or placebo. Efficacy analyses were done for the modified intent to treat population (mITT), which included all randomized patients who had baseline data, at least one dose of study drug and at least one daily seizure measurement during the maintenance period (N=217).1
Data from the study's primary endpoint showed that the high (1.0 mg/kg/day; N=49) and medium (0.5 mg/kg/day; N=58) dosages of clobazam, evaluated versus placebo (N=57), met a robust statistically significant (p≤0.01) reduction in the average weekly rate of drop seizures from the 4-week baseline period compared to the 12-week maintenance period. Patients in the high-dosage clobazam group achieved a mean decrease in average weekly rate of drop seizures of 68.3 percent (p<0.0001 vs. placebo) while those in the medium-dosage arm had an average decrease of 49.4 percent (p=0.0015 vs. placebo).1
A secondary endpoint of the study was responder rates. For each group treated with one of the three different dosages of clobazam, the percentage of patients with a decrease in average weekly rate of drop seizures of ≥25%, ≥50%, ≥75% or 100% from baseline to the maintenance period was compared to placebo. Among patients in the high-dosage arm, 77.6 percent had a 50 percent or greater reduction (p<0.01); 63.3 percent had a 75 percent or greater reduction (p<0.01); and 24.5 percent achieved 100 percent reduction. Among patients in the medium-dosage arm, 58.6 percent had a 50 percent or greater reduction (p<0.05); 37.9 percent had a 75 percent or greater reduction (p<0.01); and 12.1 percent achieved 100 percent reduction. The logistic regression model used in this study was unable to provide valid p-value estimates for the 100 percent response thresholds due to the small number of patients enrolled in this group.1

"LGS is a devastating form of epilepsy associated with multiple types of seizures, including dangerous drop seizures which may cause falls that often result in injury. This can take a tremendous toll on even the strongest families," said Joan A. Conry, MD, professor of neurology at Children's National Medical Center in Washington, D.C., and a principal investigator in the study. "While several medications are approved in the U.S. for treatment of LGS, many patients continue to have seizures due to the intractable nature of the disease. The focus on this small patient population and the results of this study provide hope for LGS patients, their families and the medical community."

The study also evaluated the effect of clobazam in decreasing total seizures (drop and non-drop) as another key secondary endpoint. Robust statistical significance was observed in patients who received the high- and medium-dosage clobazam (p<0.01 in each arm versus placebo).1
In the study, the most common treatment emergent adverse events (AEs) included somnolence, lethargy, drooling, fever, and constipation. Serious AEs occurring in ≥2 patients were lobar pneumonia and pneumonia, which occurred in both clobazam and placebo treatment arms.1
"Lundbeck makes several treatment options available in the U.S. for people affected by epilepsy, and the development of clobazam for those with LGS represents our ongoing commitment to making a difference in the lives of those affected by rare and challenging seizure disorders," said Timothy M. Cunniff, PharmD, vice president of global regulatory affairs at Lundbeck. "We are encouraged by these phase III results and look forward to submitting an NDA very soon for clobazam."

About the Study
This phase III trial was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study designed to assess the efficacy and safety of clobazam as adjunctive therapy in patients with LGS. Patient age ranged from 2-54, with a mean age at baseline of 12.4 years. Patients were included if they were being treated with one to three antiepileptic drugs (AEDs) at stable dosages for ≥30 days before screening and had ≥2 drop seizures per week during the 4-week baseline period.1
Prior to randomization, patients were stratified by weight (12.5 kg to ≤30 kg, >30 kg) and then randomized to placebo (N=59) or one of three dosages of clobazam: low (N=58 at 0.25 mg/kg/day up to a maximum of 10 mg per day), medium (N=62 at 0.5 mg/kg/day; maximum daily dosage of 20 mg per day), and high (N=59 at 1.0 mg/kg/day; maximum daily dosage of 40 mg). Of 238 patients randomized, a total of 217 comprised the modified intent to treat (mITT) population, which included all randomized patients who had baseline data, ≥1 dose of study drug, and ≥1 daily seizure measurement during the maintenance period. A total of 177 patients completed the study. Statistical significance for the primary efficacy endpoint was prespecified as p≤0.01 and considered robust statistical evidence in a single multi-center study, and p≤0.05 for secondary measures.1

About Clobazam
Clobazam is a 1,5-benzodiazepine that potentiates the inhibitory action of gamma-aminobutyric acid (GABA) by binding to GABA-A receptors.5,6 Additionally, research has identified three subtypes of the benzodiazepine omega receptor (ω).5 Diffusely distributed throughout the CNS, these ω receptors demonstrate a variety of pharmacological effects.6 In non-clinical studies, clobazam was shown to have higher affinity for the ω2 compared to the ω1 receptor.5 The precise mechanism of action by which clobazam exerts its antiepileptic effects is unknown.
The current study is part of a clinical development program to obtain FDA approval for clobazam as adjunctive treatment for patients with LGS. Clobazam is marketed outside of the U.S. in more than 100 countries under various brand names, including Frisium® or Urbanyl®. Brand names listed are property of their owners

Press release

Merck Is Ending The Isentress Phase III study, As The Drug Fails Once-a-day Treatment

 Based on the initial results of the study, which failed disappointingly, Merck the the U.S. based drugmaker announced that it was ending the Phase III study, which could have paved the way for wider use among previously untreated HIV or AIDS patients. Isentress is a leading drug for Merck and it is also one of the  fastest-growing drugs treating HIV-1 patients  . Its sales in the third quarter was $278 million, putting it on track to become a $1 billion-a-year drug for the company. Some analysts have predicted the drug to bring in 2 Billion annually by 2015.
Merck stocks took a bit of dive after the announcement. 
Following is the press release by Merck
WHITEHOUSE STATION, N.J., Nov. 29, 2010 - Merck today reported initial results from the Phase III study investigating the efficacy and safety of a treatment regimen including ISENTRESS^® (raltegravir) Tablets once daily in treatment-naïve adult patients infected with HIV-1. ISENTRESS is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-naïve and treatment-experienced adults. In the study, although the treatment regimen that included ISENTRESS once daily enabled more than 80 percent of patients to achieve viral suppression, ISENTRESS once daily did not demonstrate non-inferiority to the treatment regimen that included ISENTRESS twice daily. Merck said that based on the initial results and following the recommendation of an independent Data Monitoring Committee, Merck will end the study. Merck is notifying clinical investigators of this decision this week and is recommending that patients enrolled in the once-daily dosing arm of the study be switched to ISENTRESS twice daily, the FDA-approved dose. Results from this study will be submitted for presentation at an appropriate scientific meeting in 2011.
This Phase III study evaluated the safety and efficacy of an investigational once-daily dose of raltegravir (800 mg once daily) versus the approved twice-daily dose (400 mg twice daily), each given in combination with a once-daily fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, in adult treatment-naïve HIV-1-infected patients. In this study, 775 patients were randomized, and 770 patients received study drug and are included in the current analyses. After 48 weeks in the study, 83.2 percent (n=318/382) of patients receiving the regimen including ISENTRESS once daily achieved undetectable viral levels (HIV-RNA <50 copies/mL), compared to 88.9 percent (n=343/386) of patients receiving the regimen including ISENTRESS twice daily. The treatment difference between the 800 mg once daily group and 400 mg twice daily group was -5.7 percent, with an associated 95 percent confidence interval (CI) of (-10.7 percent, -0.83 percent). The difference did not meet the pre-defined statistical criteria for non-inferiority.
The overall treatment difference observed between the once-daily and twice-daily groups was primarily due to results in patients with high viral load. Among patients with more than 100,000 copies/mL of HIV-RNA, 74.3 percent (n=113/152) of those in the once-daily group achieved viral suppression compared to 84.2 percent (n=128/152) of those in the twice-daily group. The safety and tolerability profiles of the two regimens were similar in the study, and were consistent with current labeling for ISENTRESS.
About ISENTRESS
ISENTRESS is Merck's integrase inhibitor for the treatment of HIV-1 infection in treatment-naïve and treatment-experienced adult patients. ISENTRESS currently is the only approved integrase inhibitor for the treatment of HIV-1. The label for ISENTRESS is based on analyses of plasma HIV-1 RNA levels through 96 weeks in three double-blind controlled clinical studies of ISENTRESS. Two of these studies were conducted in clinically advanced, three-class antiretroviral (ARV) [non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), protease inhibitor (PI)] treatment-experienced adults and one was conducted in treatment-naïve adults. The safety and efficacy of ISENTRESS have not been established in pediatric patients. The use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response.
ISENTRESS is the first medicine to be approved in a class of antiretroviral drugs called integrase inhibitors. ISENTRESS works by inhibiting the insertion of HIV-1 DNA into human DNA by the integrase enzyme and has demonstrated rapid antiviral activity. Inhibiting integrase from performing this essential function limits the ability of the virus to replicate and infect new cells. Other HIV-1 drugs in use inhibit two other enzymes critical to the HIV-1 replication process – protease and reverse transcriptase – but ISENTRESS is the only approved drug that inhibits the integrase enzyme. ISENTRESS is now approved in more than 90 countries worldwide. Merck is continuing to move forward with filings in additional countries around the world for use of ISENTRESS in both treatment-experienced and treatment-naïve HIV-infected patients.
Important safety information about ISENTRESS
ISENTRESS does not cure HIV or AIDS and does not prevent passing HIV to others. Healthcare providers should know that immune reconstitution syndrome has been reported in patients treated with ARV therapy, which may necessitate further evaluation and treatment.
Creatine kinase elevations were observed in subjects who received ISENTRESS. Myopathy and rhabdomyolysis have been reported. ISENTRESS should be used with caution in patients at increased risk of myopathy or rhabdomyolysis, such as patients receiving concomitant medication known to cause these conditions.
The most commonly reported drug-related adverse event (AE) of moderate to severe intensity that occurred in greater than or equal to 2 percent of patients and at a higher incidence than efavirenz in treatment-naïve patients receiving ISENTRESS was insomnia (4 percent versus 3 percent, respectively).
The most commonly reported (greater than or equal to 2 percent in either treatment group) drug-related clinical AE of moderate or severe intensity in treatment-experienced patients receiving ISENTRESS and at a higher rate compared to placebo was headache (2 percent vs. less than 1 percent) for ISENTRESS plus optimized background therapy (OBT) and placebo plus OBT, respectively.
In treatment-experienced patients, rash occurred more often in patients taking ISENTRESS and darunavir together than with either drug separately. Rashes were mild to moderate in severity and did not limit therapy. There were no discontinuations due to rash.
Dosing and administration
ISENTRESS is a single 400 mg tablet taken twice daily without regard to food. The dose of ISENTRESS should be increased during coadministration with rifampin to 800 mg twice daily.
Drug interactions
Co administration with strong inducers of uridine diphosphate glucuronosyltransferase (UGT) 1A1 may reduce plasma concentrations of ISENTRESS. Rifampin, a strong inducer of (UGT) 1A1 reduces plasma concentrations of ISENTRESS. Based on the results of drug interaction studies and the clinical trials data, no dose adjustment of ISENTRESS is required when co administered with other ARV agents. Also, preclinical studies show that ISENTRESS is not metabolized by cytochrome P450 enzymes.
For more information, visit www.merck.com.