GlaxoSmithKline and Theravance announce expansion of the Horizon programme with start of large Phase 2B study of LABA in COPD patients

GlaxoSmithKline Plc (GSK) and Theravance, Inc. (NASDAQ: THRX) today announced the expansion of the Horizon programme into development of a next-generation combination treatment for patients with chronic obstructive pulmonary disorder (COPD). A large Phase 2b COPD dose-optimisation study with the lead long-acting beta agonist (LABA) GW642444 (‘444) has commenced, with screening of the first patient undertaken.

This is in addition to the four large Phase 2b asthma dose-optimisation studies; one with ‘444 and three with the lead inhaled corticosteroid (ICS) GW685698 (‘698), which commenced in December 2007, as part of the ongoing Horizon programme.

Darrell Baker, SVP GSK Respiratory Medicines Development Centre said, “Delivering a once-daily treatment for asthma and COPD, where there remains a considerable unmet need, is a priority. We believe that this is an important milestone within the Horizon programme and we eagerly await results from the ongoing asthma and now COPD studies that will help guide future development of these important assets.”

“We are very pleased to have initiated the larger Phase 2b study with the lead compound ‘444 in COPD," said Rick E Winningham, Chief Executive Officer at Theravance. “With ‘444 now in large Phase 2b studies in both asthma and COPD, we have met two important targets that bring us closer to our joint goal of bringing a new treatment option to patients in these important therapeutic areas."

Study design
This double-blind, placebo controlled trial will enrol approximately 600 patients with moderate to severe COPD from study centres across the USA, Europe and international locations. Each patient will be randomised to receive a once-daily dose of placebo or ‘444 via a novel inhaler throughout the 28-day treatment period. The primary endpoint of the study will be efficacy, evaluated by change from baseline FEV1 (pre-bronchodilator and pre-dose) at the end of the 28-day treatment period, with a number of secondary endpoints also evaluated.

These study data, taken together with the data obtained from parallel studies currently being undertaken with ‘698, will be used to guide future development plans in COPD and progression into large-scale Phase 3 COPD combination studies. No Phase 2b COPD monotherapy studies with ‘698 will be undertaken as part of the Horizon programme.

About GSK
GlaxoSmithKline is one of the world’s leading research-based pharmaceutical and healthcare companies. GlaxoSmithKline is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information visit www.gsk.com.

About Theravance
Theravance is a biopharmaceutical company with a pipeline of internally discovered product candidates. Theravance is focused on the discovery, development and commercialization of small molecule medicines across a number of therapeutic areas including respiratory disease, bacterial infections and gastrointestinal motility dysfunction. Of the six programs in development, four are in late stage - its telavancin program focusing on treating serious Gram-positive bacterial infections with Astellas Pharma Inc., the Horizon program with GlaxoSmithKline plc, the Gastrointestinal Motility Dysfunction program, and TD-1792, an investigational antibiotic for the treatment of serious Gram-positive bacterial infections. By leveraging its proprietary insight of multivalency toward drug discovery focused primarily on validated targets, Theravance is pursuing a next generation strategy designed to discover superior medicines in areas of significant unmet medical need. For more information, please visit the company's web site at www.theravance.com. THERAVANCE®, the Theravance logo, and MEDICINES THAT MAKE A DIFFERENCE® are registered trademarks of Theravance, Inc.

Medtronic Statement Regarding Senate Hearings on Industry And Physician Relationships

In advance of hearings on Wednesday, February 27, in the Senate Special Committee on Aging, Medtronic, Inc. (NYSE:MDT), today issued the following statement:

On Wednesday, February 27, the Senate Special Committee on Aging will explore relationships between industry and physicians and consider the proposed “Sunshine Act” (S.2029) introduced earlier this year by Senators Chuck Grassley (R-IA) and Herb Kohl (D-WI).

The Sunshine Act would require industry to publicly disclose via the Internet certain payments made to physicians in return for their time and expertise with product development, research and training. For decades, the innovative power and clinical expertise of physicians have produced technologies that industry has brought to patients around the world, and Medtronic believes these vital collaborations must be protected

The Sunshine Act is aimed at curbing inappropriate relationships or conflicts of interests between industry and physicians, an effort that Medtronic – one of the world’s leading medical technology companies – supports.

Medtronic believes, however, the bill can and should go even further by requiring the same level of disclosure by all companies in the industry, regardless of size and including those companies owned in whole or in part by physicians. Companies with yearly revenues less than $100 million and physician-owned companies are currently excluded from the bill, and they account for more than 75 percent of the companies in the industry.

Medtronic believes a level playing field for all companies is appropriate and that these entities should operate under the same disclosure requirements, recognizing that transparency can help alleviate any real or perceived conflicts of interest with these types of companies as well.

“We have been pleased to work with the members of the Senate Special Committee on Aging, the Senate Finance Committee, and members of the House of Representatives and Senate on this legislation,” said Bill Hawkins, president and CEO of Medtronic. “We will continue to work with the sponsors of this legislation to incorporate all companies in the industry into the bill and bring greater transparency to these important relationships.”

About Medtronic

Medtronic, Inc. (www.medtronic.com), headquartered in Minneapolis, is the global leader in medical technology – alleviating pain, restoring health and extending life for millions of people around the world.

Invitrogen Renews, Expands License and Supply Agreement with Luminex

Invitrogen Corporation (NASDAQ: IVGN), a provider of essential life science technologies for research, production and diagnostics, and Luminex Corporation (NASDAQ: LMNX), today announced the renewal and expansion of Invitrogen's license and supply agreement for Luminex's multiplexed analyte detection technology and systems. The new agreement extends the lifetime of the license and provides Invitrogen with access to Luminex's next-generation multiplex detection platforms.

xMAP(R) Technology and Luminex instrument platforms use proprietary microspheres - micron-sized beads - encoded with combinations of spectrally distinct fluorescent dyes to rapidly and reproducibly determine the relative concentrations of many different proteins or peptides at the same time in the same sample.

Invitrogen offers more than 200 assays based on xMAP Technology, comprising the most comprehensive multiplex protein assay menu in life sciences for cellular pathway and disease analysis. Invitrogen also has a large number of new multiplexed assays in its product development pipeline to expand the number of targets accessible to scientists. The company will offer custom assay development services using the next-generation platform that complement its existing service of rapid, affordable multiplex assay development on the original Luminex platform.

"We are pleased with this new agreement and committed to our relationship with Luminex," said Kip Miller, Invitrogen's Senior Vice President, BioDiscovery. "It is another step in our strategy of building on our position as the leading cell biology reagent provider to offer our customers integrated systems and solutions."

"We believe the extension of the agreement is beneficial for both companies, as Luminex has quickly become a standard in the industry for multiplexing and Invitrogen has the ability to offer the broadest array of content for this important platform," added August Sick, Invitrogen Vice President and General Manager, Cellular Analysis Business Unit. "The assays we will develop on Luminex's next-generation platform will further accelerate drug discovery and cellular analysis."

"Luminex is pleased to extend and expand our relationship with Invitrogen," said Doug Bryant, executive vice president and chief operating officer of Luminex. "Partnering with innovative leaders such as Invitrogen is a key element in our business strategy. We look forward to a valuable, long-term collaboration with Invitrogen."

Invitrogen, Agilent Technologies Settle Multiple Patent Litigations

Invitrogen Corporation and Agilent Technologies have jointly announced a confidential settlement of multiple patent litigations pending between the two companies. The settlement resolves three patent infringement lawsuits between Invitrogen and Stratagene, Inc. Agilent acquired Stratagene in 2007.

These patent litigations between the companies had been pending since 2000 and 2001. In June 2000, Invitrogen sued Stratagene in the United States District Court for the District of Maryland, Southern Division, for infringement of Invitrogen's U.S. Patent Nos. 6,063,608, 5,244,797, and 5,405,776 relating to the use and sale of RNase H minus reverse transcriptase (RT) products. This case had been stayed pending resolution of a related litigation with Clontech.

On March 12, 2001, Invitrogen filed suit against Stratagene for infringement of U.S. Patent No. 4,981,797. That patent covers a process for producing E. coli cells that are more effective at absorbing foreign DNA and thereby more "competent." In 2006, the United States District Court for the Western District of Texas, Austin Division, entered judgment awarding Invitrogen $16.2 million plus prejudgment interest, post-judgment interest, attorneys' fees and costs, and entered an injunction against further infringement. Stratagene appealed the judgment to the United States Court of Appeals for the Federal Circuit.

In November 2001, Stratagene filed suit against Invitrogen in the United States District Court for the District of Maryland, Southern Division, for infringement of U.S. Patent No. 5,556,772 related to the use and sale of certain DNA polymerase blend products. The case had been stayed by the Court pending a reissuance proceeding before the United States Patent Office.

Under the terms of the agreement, Agilent will make an undisclosed settlement payment to Invitrogen. In addition, Agilent will discontinue sales of its RNase H minus RT products and Invitrogen will obtain a license from Agilent and pay an undisclosed royalty to sell its DNA polymerase blend products. All litigation will be dismissed. No other details of the settlement were disclosed.

About Invitrogen

Invitrogen Corporation (Nasdaq:IVGN) provides products and services that support academic and government research institutions and pharmaceutical and biotech companies worldwide in their efforts to improve the human condition. The company provides essential life science technologies for disease research, drug discovery, and commercial bioproduction. Invitrogen's own research and development efforts are focused on breakthrough innovation in all major areas of biological discovery including functional genomics, proteomics, bioinformatics and cell biology -- placing Invitrogen's products in nearly every major laboratory in the world. Founded in 1987, Invitrogen is headquartered in Carlsbad, California, and conducts business in more than 70 countries around the world. The company employs approximately 4,700 scientists and other professionals and had revenues of approximately $1.3 billion in 2007. For more information, visit www.invitrogen.com.

About Agilent Technologies

Agilent Technologies Inc. (NYSE: A) is the world's premier measurement company and a technology leader in communications, electronics, life sciences and chemical analysis. The company's 19,000 employees serve customers in more than 110 countries. Agilent had net revenues of $5.4 billion in fiscal 2007. Information about Agilent is available on the Web at www.agilent.com.

Study Suggests Risperidone Long-Acting Injection Combined with Standard Treatment Helped Delay Time to Relapse in Patients with Bipolar Disorder

Patients with frequently relapsing bipolar disorder had a significant delay in the time to an initial relapse when risperidone long-acting injection (RLAI) was combined with standard treatment, according to a new study. The study compared patients who received RLAI and standard treatment to those who received standard treatment combined with placebo.

The study was presented yesterday at the 14th Biennial Winter Workshop on Schizophrenia and Bipolar Disordersin Montreux, Switzerland.1 This one-year, phase 3, trial is the first placebo-controlled study to explore the use of a long-acting injection medication in the maintenance treatment of frequently relapsing bipolar disorder (FRBD). FRBD, defined as four or more manic or depressive episodes in the previous year that require a doctor's care, may affect 20% of the 27 million people with bipolar disorder worldwide.2, 3

The study compared the time to the next mood episode, also known as a relapse, in FRBD patients receiving RLAI plus standard treatment vs. patients receiving placebo plus standard treatment. For most patients, standard treatment consisted of mood stabilizers, antidepressants, anxiolytics or combinations thereof. The trial showed that time to relapse was significantly longer in patients receiving RLAI compared with placebo (p=0.004) and the relative risk of relapse was 2.4 times higher with placebo. The relapse rates were 47.8% with placebo and 22.2% with RLAI.

"Patients with frequently relapsing bipolar disorder require more healthcare interventions than patients with fewer episodes, and there is a huge unmet need for new treatments," said Dr. Joseph Calabrese, Co-Director of the Bipolar Disorders Research Center, University Hospitals Case Medical Center, Case Western Reserve University. Dr. Calabrese is a consultant to the study sponsors, Ortho-McNeil Janssen Scientific Affairs, L.L.C. "Risperidone long-acting injection is administered once every two weeks by a healthcare professional and avoids the need for patients to remember to take daily antipsychotic medications. "

In the study, 139 patients were randomized to receive either RLAI 25-50mg intramuscular injection (n=72), or placebo injections (n=67) adjunctive to standard treatment. Patients receiving RLAI plus standard treatment were eligible to enter the double blind phase of the trial if they met predefined criteriaa for being stable the last four weeks of the 16-week open-label stabilization phase.

In the study, Frequently Relapsing Bipolar Disorder: Evidence for an Effective Treatment Using Adjunctive Risperidone Long-Acting Injectable, 67% of patients randomized received a 25 mg dose of RLAI, 29% received a 37.5 mg dose and 4% received a 50 mg dose, administered once every two weeks.

The primary efficacy endpoint in the double-blind phase of the trial was the time from randomization to relapse, where relapse was defined as the first occurrence of a mood episode as determined by an independent Relapse Monitoring Board (RMB).b

The results showed a significant difference in time to relapse (p=0.004), with a more than two-fold higher risk of relapse in the placebo group (47.8%) than the RLAI group (22.2%). In addition, scores on the Clinical Global Impression–Bipolar–Severity (CGI-BP-S) scale for overall bipolar disorder and the Clinical Global Impression-Bipolar-Change (CGI-BP-C) scale worsened significantly (p<0.05) in the placebo group compared with the RLAI group.

Treatment-emergent adverse effects (TEAEs) occurred more frequently in the group that received placebo and standard treatment (76.1%) than in the group that received RLAI and standard treatment (70.8%), as did serious adverse effects (placebo=19.4%; RLAI = 13.9%). The most common TEAEs (greater than 5%) in the double-blind phase were tremor (RLAI = 23.6%; placebo = 16.4%), insomnia (RLAI = 19.4%; placebo = 23.9%), muscle rigidity (RLAI = 11.1%; placebo = 6%); weight gain (RLAI = 6.9%; placebo = 1.5%) and hypokinesia (RLAI = 6.9%; placebo = 0%). A total of 5 patients discontinued due to adverse events in the double-blind phase (3 in the RLAI group and 2 in the placebo group).

Risperidone long-acting injection is marketed in the U.S. by Janssen, Division of Ortho-McNeil Janssen Pharmaceuticals, Inc. The formulation is manufactured by Alkermes, Inc. (Nasdaq: ALKS). Ortho-McNeil Janssen Scientific Affairs, LLC, funded the study.

About Bipolar Disorder

It is estimated that 27 million people worldwide2 suffer from bipolar disorder, also known as manic-depressive disorder. It is characterized by debilitating mood swings, from extreme highs (mania) to extreme lows (depression). Signs of mania include euphoria, extreme irritability or rage, accelerated or disorganized thinking and an increase in risky behaviors. Signs of depression include intense sadness or despair, loss of energy, insomnia and suicidal thoughts.

A classification of patients identified as "rapid-cycling" and also having four or more episodes during the previous 12 months, is estimated to occur in approximately 10-20% of patients with bipolar disorder seen in mood disorder clinics. The types of mood episodes (manic, depressed, mixed) seen in these patients can occur in any pattern. The course of their illness is characterized by a requirement for more health care resources, more concomitant medications and poorer outcomes.4

About Risperidone Long-Acting Injection

Risperidone long-acting injection is the first and only long-acting, atypical antipsychotic to be approved by the U.S. Food and Drug Administration and now is approved in more than 70 countries worldwide. The treatment uses Alkermes proprietary Medisorb® technology to deliver and maintain therapeutic medication levels in the body through just one injection every two weeks. Janssen markets Risperidone long-acting injection in the United States. The formulation is manufactured by Alkermes, Inc. (Nasdaq: ALKS). Available in 12.5 mg, 25 mg, 37.5 mg and 50 mg dose units, it is approved for the treatment of schizophrenia. For more information about RISPERDAL CONSTA, visit www.risperdalconsta.com.

Janssen, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., is based in Titusville, N.J. and is the only large pharmaceutical company in the U.S. dedicated solely to mental health. As the company celebrates its 50th year in mental health, it currently markets prescription medications for the treatment of schizophrenia, bipolar mania and the treatment of symptoms associated with autistic disorder. For more information about Janssen, visit www.janssen.com.

Alkermes, Inc. is a biotechnology company that uses proprietary technologies and know-how to create innovative medicines designed to yield better therapeutic outcomes for patients with serious disease. Alkermes manufactures RISPERDAL® CONSTA®, marketed by Janssen, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. in the U.S. and Janssen-Cilag, a subsidiary of Johnson & Johnson, outside of the U.S. Alkermes also developed and manufactures VIVITROL®, marketed in the U.S. primarily by Cephalon, Inc. The company's pipeline includes extended-release injectable, pulmonary and oral products for the treatment of prevalent, chronic diseases, such as central nervous system disorders, addiction and diabetes. Alkermes is headquartered in Cambridge, Massachusetts, with research and manufacturing facilities in Massachusetts and Ohio. For more information about Alkermes, visit www.alkermes.com.

a Stable remission was achieved if, during the last 4 weeks of the 16-week OL stabilization phase the subject had not met DSM-IV-TR criteria for active mood disorder; the subject had no crisis interventions; the subject’s Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS) total scores both remained ≤10 and the Clinical Global Impression – bipolar severity (CGI-BP-S) score remained ≤ 3 and the subject’s medications and doses of other psychotropic medications remained unchanged.

b RMB = a fully independent, blinded, international board of 3 psychiatrists considered experts in the treatment of bipolar disorder. They reviewed all clinical data and determined whether the patient met relapse criteria.

References

1 Aphs L, Kujawa M, Macfadden W et al., Frequently relapsing bipolar disorder: evidence for an effective treatment using adjunctive risperidone long-acting injectable, presented at the 14th Biennial Winter Workshop on Schizophrenia, Montreux, Switzerland, February 2008.

2 The Global Burden of Disease. World Health Organization, 2003. Available at
http://www.who.int/mip/2003/other_documents/en/globalburdenofdisease.pdf, accessed January 18, 2008

3 DSM-IV-TR, American Psychiatric Association, 2000.

4 DSM-IV, American Psychiatric Association, 2000