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Allos Therapeutics, Inc. (Nasdaq: ALTH) announced that an independent Data Monitoring Committee (DMC) has completed the pre-specified 65-patient safety review of data from the Company’s pivotal Phase 2 PROPEL trial of PDX (pralatrexate) in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), and has recommended that the trial continue per the protocol. This interim assessment was based upon an evaluation of patients enrolled in the study who completed at least one cycle of treatment with PDX. The Company currently expects to complete patient enrollment in the PROPEL study in the second quarter of 2008.

“The DMC recommendation represents another important milestone in the development of a potential new treatment option for patients with relapsed or refractory peripheral T-cell lymphoma, a patient population for which there are currently no approved agents,” said Pablo J. Cagnoni, M.D., Senior Vice President and Chief Medical Officer of Allos. “We remain pleased with the progress of the PROPEL trial and look forward to continuing to drive our PDX product development and commercialization plans in 2008.”

PROPEL (Pralatrexate in Patients with Relapsed Or Refractory PEripheral T-cell Lymphoma) is a pivotal Phase 2, international, multi-center, open-label, single-arm study that will seek to enroll a minimum of 100 evaluable patients with relapsed or refractory PTCL who have progressed after at least one prior treatment. Patients receive 30 mg/m2 of PDX once every week for six weeks followed by one week of rest per cycle of treatment. The primary efficacy endpoint of the study is objective response rate (complete and partial response). Secondary efficacy endpoints include duration of response, progression-free survival and overall survival.

Owen A. O’Connor, MD, PhD, Director, Lymphoid Development & Malignancy Program and Chief, Lymphoma Service, Columbia University, Herbert Irving Comprehensive Cancer Center, New York, is the international study chair.

In accordance with the PROPEL study design, in January 2007, the DMC completed an interim analysis of safety data based on the first 10 patients enrolled to the study who completed at least one cycle of treatment with PDX, and recommended that the trial continue per the protocol. Also in accordance with the study design, in September 2007, an interim analysis of patient response and safety data was conducted based on the first 35 patients enrolled to the study who completed at least one cycle of treatment with PDX. The results of the interim analysis of patient response data exceeded the pre-specified threshold for continuation of the trial, which required a minimum of four responses (complete or partial) out of the first 35 evaluable patients, as determined by independent oncology review. In addition, the DMC identified no major safety concerns and recommended that the trial continue per the protocol.

The PROPEL trial is being conducted under an agreement with the United States Food and Drug Administration (FDA) under its special protocol assessment (SPA) process. The SPA process allows for FDA evaluation of a clinical trial protocol intended to form the primary basis of an efficacy claim in support of an NDA, and provides an agreement that the study design, including trial size, clinical endpoints and/or data analyses are acceptable to the FDA. The FDA granted orphan drug designation to PDX for the treatment of T-cell lymphoma in July 2006 and granted fast track designation to PDX for the treatment of patients with T-cell lymphoma in September 2006. In April 2007, the Commission of the European Communities, with a favorable opinion of the Committee for Orphan Medicinal Products of the European Medicines Agency, or EMEA, granted orphan medicinal product designation to PDX for the treatment of patients with PTCL

Background In an open-label, randomized, phase 3 trial, we compared the efficacy and safety of paclitaxel with that of paclitaxel plus bevacizumab, a monoclonal antibody against vascular endothelial growth factor, as initial treatment for metastatic breast cancer.

Methods We randomly assigned patients to receive 90 mg of paclitaxel per square meter of body-surface area on days 1, 8, and 15 every 4 weeks, either alone or with 10 mg of bevacizumab per kilogram of body weight on days 1 and 15. The primary end point was progression-free survival; overall survival was a secondary end point.

Results From December 2001 through May 2004, a total of 722 patients were enrolled. Paclitaxel plus bevacizumab significantly prolonged progression-free survival as compared with paclitaxel alone (median, 11.8 vs. 5.9 months; hazard ratio for progression, 0.60; P<0.001) and increased the objective response rate (36.9% vs. 21.2%, P<0.001). The overall survival rate, however, was similar in the two groups (median, 26.7 vs. 25.2 months; hazard ratio, 0.88; P=0.16). Grade 3 or 4 hypertension (14.8% vs. 0.0%, P<0.001), proteinuria (3.6% vs. 0.0%, P<0.001), headache (2.2% vs. 0.0%, P=0.008), and cerebrovascular ischemia (1.9% vs. 0.0%, P=0.02) were more frequent in patients receiving paclitaxel plus bevacizumab. Infection was more common in patients receiving paclitaxel plus bevacizumab (9.3% vs. 2.9%, P<0.001), but febrile neutropenia was uncommon (<1% overall).

Conclusions Initial therapy of metastatic breast cancer with paclitaxel plus bevacizumab prolongs progression-free survival, but not overall survival, as compared with paclitaxel alone. (ClinicalTrials.gov number, NCT00028990 [ClinicalTrials.gov] .)

Discussion

In this phase 3 trial of paclitaxel plus bevacizumab as the initial treatment of metastatic breast cancer, the safety profile of the combination was similar to profiles reported in previous randomized trials.8,16,17,18 Most toxic effects were minimal, rarely limited therapy, and did not have a detrimental effect on overall quality of life.15

We enrolled patients with predominantly HER2-negative breast cancer; no patient received concurrent trastuzumab. Further studies are needed to assess the efficacy of bevacizumab in patients with HER2-positive metastatic breast cancer.19,20 In our trial, bevacizumab was not given to patients who had a tumor with a specific molecular phenotype. Although benefit was seen across a number of clinically important subgroups, our results would be strengthened by the ability to identify patients most likely to benefit from VEGF-directed therapies.

In a previous phase 3 study, the addition of bevacizumab to capecitabine significantly increased the objective response rate but not progression-free survival or overall survival.8 What might account for the different results in these trials? It seems unlikely that chance could account for the improvement in progression-free survival found in our trial. Investigator or patient bias, always a consideration in open-label studies, is unlikely to explain our results. If such biases had a large role, we would have expected to see a greater improvement in patients with nonmeasurable lesions, where disease assessment is necessarily subjective. Actually, the hazard ratio was more favorable in patients with measurable disease than in those with nonmeasurable disease (0.55 vs. 0.68).

Substantial differences between the patient populations of these studies may account for the disparate results. All patients in the earlier study had received previous anthracycline and taxane therapy, and most (more than 85%) had received chemotherapy for metastatic disease.8 In contrast, 35.2% of our patients had not received any previous chemotherapy, and only 13.2% had received both an anthracycline and a taxane as adjuvant therapy.

A recent phase 2 trial found a median time to disease progression of only 5.7 months (95% confidence interval, 4.9 to 8.4) with capecitabine plus bevacizumab as initial chemotherapy.21 Perhaps paclitaxel is uniquely synergistic with bevacizumab. Indeed, the taxanes have distinct antiangiogenic activity.22 In preclinical studies, VEGF protected endothelial cells from the antiangiogenic properties of docetaxel; bevacizumab overcame this protective effect in vitro and in vivo.23

Despite a striking improvement in progression-free survival, the addition of bevacizumab did not prolong overall survival in this study. Patients with metastatic breast cancer frequently receive multiple therapies during the course of their disease. Data on treatment administered after progression were not collected in this trial, precluding an exploratory analysis of the influence of subsequent therapy on overall survival. Though the mechanisms of resistance to bevacizumab are not well defined,24,25 it is possible that resistance to bevacizumab results in relative resistance to subsequent therapies. Alternatively, rebound increases in VEGF on discontinuation of bevacizumab could result in more aggressive disease. Resistance to paclitaxel, whether mediated by increased expression of the multidrug resistance protein26 or by microtubule mutations,27 could also cause resistance to subsequent chemotherapy.

We found that treatment with bevacizumab early in the course of metastatic breast cancer, when angiogenic pathways are less redundant, improved progression-free survival and the objective response rate. Although our patients were receiving their first treatment for metastatic breast cancer, only a third had never received any chemotherapy. More than 80% had overt visceral involvement, presumably with an established vasculature. In short, first-line therapy for metastatic breast cancer is not “early” in the natural history of breast cancer. Recent laboratory studies suggest that the initial events in the development of metastasis are VEGF-dependent.28,29 If this is true, the most successful clinical application of angiogenesis inhibitors is likely to be in patients with micrometastatic disease in the adjuvant setting.

Supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA49883, and CA16116 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and by Genentech.

Dr. Miller reports receiving lecture fees and consulting fees for service on breast cancer advisory boards from Roche. Dr. Gralow reports receiving lecture fees and consulting fees for service on breast cancer advisory boards from Genentech and Roche. Dr. Dickler and Dr. Cobleigh report receiving consulting fees from Genentech for service on breast cancer advisory boards. Dr. Cobleigh reports receiving lecture fees from Genentech. Dr. Perez reports receiving consulting fees from Genentech, GlaxoSmithKline, Bristol-Myers Squibb, and Sanofi-Aventis for service on breast cancer advisory boards, as well as grant support for clinical translational studies from Genentech. No other potential conflict of interest relevant to this article was reported.

The views expressed are those of the authors and do not necessarily represent the official views of the National Cancer Institute.

We thank Dr. George Sledge and Dr. Robert Gray for helpful discussions and Carol Chami for providing technical assistance in preparing the manuscript.

Source Information

From Indiana University Cancer Center, Indianapolis (K.M.); Dana–Farber Cancer Institute, Boston (M.W.); Puget Sound Oncology Consortium, Seattle (J.G.); Memorial Sloan-Kettering Cancer Center, New York (M.D.); Rush–Presbyterian–St. Luke’s Medical Center, Chicago (M.C.); Mayo Clinic, Jacksonville, FL (E.A.P.); British Columbia Cancer Agency–Vancouver Cancer Center, Vancouver, BC, Canada (T.S.); Evanston Northwestern Healthcare and Robert H. Lurie Comprehensive Cancer Center of Northwestern University — both in Evanston, IL (D.C.); and Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore (N.E.D.).

Address reprint requests to Dr. Miller at the Indiana Cancer Pavilion, 535 Barnhill Dr., RT473, Indianapolis, IN 46202, or at kathmill@iupui.edu.

Among breast cancer patients, both chemotherapy and tamoxifen independently reduced the risk of developing a second cancer in the other breast, according to a study published online December 25 in the Journal of the National Cancer Institute. The risk reduction persisted for at least 10 and 5 years, respectively.

For breast cancer patients the risk of developing cancer in the other breast is two to six times greater than the breast cancer risk of the general public. Studies have shown that taking tamoxifen for five years reduces the risk of cancer in the opposite breast among women who have estrogen receptor-positive breast cancer, but the studies did not clarify how long the protective effect lasts.

Lisbeth Bertelsen, M.D., of the Danish Cancer Society in Copenhagen and colleagues investigated the relationship between tamoxifen and chemotherapy - either alone or in combination - and the risk of cancer in the opposite breast among American and Danish women who were first diagnosed with breast cancer before age 55. The study included 1,158 women who developed cancer in one breast and an additional 634 who initially had cancer in one breast then developed a second cancer in the other breast.

The chemotherapy treatment was associated with a 43 percent reduced risk for developing cancer in the opposite breast, compared with no chemotherapy. This risk reduction lasted up to 10 years after the initial cancer diagnosis and was stronger among women who entered menopause within a year of their diagnosis. Tamoxifen use was associated with a 34 percent reduced risk of a second breast cancer, compared with no tamoxifen use, and this reduction continued for five years after diagnosis.

“Ovarian suppression caused by chemotherapy may have a role in the association, possibly in combination with a cytotoxic effect on [breast tumor cells],” the authors write.

“Effect of Systemic Adjuvant Treatment on Risk for Contralateral Breast Cancer in the Women’s Environment, Cancer and Radiation Epidemiology Study”
Lisbeth Bertelsen, Leslie Bernstein, Jørgen H. Olsen, Lene Mellemkjær, Robert W. Haile, Charles F. Lynch, Kathleen E. Malone, Hoda Anton-Culver, Jane Christensen, Bryan Langholz, Duncan C. Thomas, Colin B. Begg, Marinela Capanu, Bent Ejlertsen, Marilyn Stovall, John D. Boice, Jr, Roy E. Shore, The Women’s Environment, Cancer and Radiation Epidemiology Study Collaborative Group, Jonine L. Bernstein
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djm267

GlaxoSmithKline (GSK) announced that Tyverb® (lapatinib) has received a positive opinion recommending a conditional marketing authorisation from the European Medicines Agency (EMEA). Lapatinib, in combination with capecitabine, is indicated for the treatment of patients with advanced or metastatic breast cancer whose tumours over-express ErbB2 (HER2). Patients should have progressive disease following prior therapy which must include anthracyclines, taxanes and therapy with trastuzumab in the metastatic setting.[1]

Lapatinib is the first oral, small molecule dual targeted therapy that works by getting inside the cancer cell to inhibit both ErbB1 (EGFR) and ErbB2 (HER2), two receptor proteins which are responsible for tumour growth.[2] This novel mechanism of action is a new way to treat breast cancer.

“This positive opinion is fantastic news for eligible women with ErbB2-positive breast cancer across the European Union. Thousands of women are diagnosed every year in Europewith ErbB2 positive breast cancer and are at a greater risk of disease progression and death compared to women with tumours that do not over-express this protein,” said Dr Martine Piccart, Professor of Oncology, Université Libre de Bruxelles and Department Head, Medicine, Jules Bordet Institute, Brussels. “Lapatinib represents an important new treatment option for a group of patients in real need of alternative therapies and I look forward to the day that I can prescribe lapatinib. Not only that, but this is just the beginning given the ongoing clinical programme investigating the potential use of lapatinib in earlier stages of the disease.”

The data submitted

The positive opinion was based on a pivotal Phase III trial (EGF100151) in which women with advanced or metastatic ErbB2-positive breast cancer whose disease had progressed following prior treatment were given either the combination of lapatinib and capecitabine, or capecitabine alone. The data showed that the analysis of investigator reported median time to progression (TTP) was 23.9 weeks in the lapatinib and capecitabine arm versus 18.3 weeks in the capecitabine arm alone (hazard ratio = 0.72 p=0.00762).[3] Significance was also shown in the independently assessed time to progression data (hazard ratio 0.57; p=0.00013).[4],[5],[6]

In addition to the achievement of the primary endpoint, results from the trial demonstrated the associated potential to reduce the incidence of brain metastases as the first site of recurrence in metastatic breast cancer. Progression of brain metastases was 2% in the combination arm compared with 6% in the capecitabine alone arm.[7] Central nervous system metastases are a major burden for breast cancer patients.[8] These preliminary results with lapatinib are encouraging and are the basis of ongoing research in this area. Latest data on the use of lapatinib and capecitabine in brain metastases will be presented at the San Antonio Breast Cancer Symposium (SABCS) on 16 December 2007.

The most common adverse events during therapy with lapatinib plus capecitabine were gastrointestinal (diarrhoea, nausea and vomiting) or skin disorders (rash and hand and foot syndrome). The majority of adverse events were mild to moderate in severity and were not significantly higher than those seen with capecitabine monotherapy.5

A conditional marketing authorisation is granted to a medicinal product that fulfils an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required. In the case of lapatinib, GSK is to provide further data from the pivotal study and also additional demonstration of decreased incidence of relapse in the central nervous system, for which a study will be conducted. A conditional marketing authorisation is valid for one year. Thereafter, the conditional marketing authorisation may be renewed annually.

“This is an extremely significant development for patients and physicians across Europe as lapatinib, in combination with capecitabine, will play a valuable role in treating an especially aggressive form of advanced breast cancer by providing an effective treatment that offers added convenience as an oral therapy,” said Paolo Paoletti, SVP and Global Head of the Oncology Medicine Development Centre at GSK.

Andrew Witty, President, Pharmaceuticals Europe, GSK and CEO designate added, “The innovative mechanism of action of lapatinib represents a new way to treat breast cancer patients. It is also important to note that this is GSK’s second EMEA positive opinion for a cancer treatment in a matter of months, following the positive opinion and approval of Atriance® (nelarabine) in the summer. These positive opinions underscore our commitment to develop an industry leading oncology portfolio to address the unmet medical needs of cancer patients, whether they be for highly prevalent or extremely rare forms of the disease.”

Future for lapatinib onoing clinical trials

A comprehensive clinical development programme will evaluate lapatinib both alone and in combination with other therapies (chemotherapy, hormonal therapy, other targeted agents and VEGF inhibitors) across the spectrum of ErbB2-positive breast cancer, from metastatic to early breast cancer. Trials are also ongoing and planned in a range of other solid tumours that over-express ErbB1 and/or ErbB2.

Researchers developed a new method for distinguishing between breast cancer recurrences and new primary tumors.

One commonly used method is to detect changes in DNA copy number. Another is to compare clinical and pathologic characteristics of the two tumors.

Marc Bollet, M.D., of the Institut Curie in Paris and colleagues compared these two methods with a new method that uses DNA breakpoint data by assessing their ability to distinguish between breast cancer recurrence and new primary tumors in 22 breast cancer patients.

For 14 women, all three methods agreed on whether the tumor was a new primary tumor or a recurrence. The DNA breakpoints method more often agreed with the clinical and pathologic method than did the DNA copy number method. The DNA breakpoints method also outperformed the clinical method in determining the likelihood of metastasis.

The authors concluded that DNA breakpoints could better determine the nature of the breast cancer recurrence than clinical and pathologic characteristics or DNA copy number information.

“High-Resolution Mapping of DNA Breakpoints to Define True Recurrences Among Ipsilateral Breast Cancers”
Marc A. Bollet, Nicolas Servant, Pierre Neuvial, Charles Decraene, Ingrid Lebigot, Jean-Philippe Meyniel, Yann De Rycke, Alexia Savignoni, Guillem Rigaill, Philippe Hupé, Alain Fourquet, Brigitte Sigal-Zafrani, Emmanuel Barillot, Jean-Paul Thiery
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djm266

ScienceDaily (Dec. 26, 2007) — A group of signaling proteins known as Wnt - which help build the human body’s skin, bone, muscle and other tissues - depend on a complex delivery and recycling system to ensure their transport to tissue-building cell sites, according to a study at Cincinnati Children’s Hospital Medical Center. When the recycling system - the Retromer Complex - breaks down, the delivery of this specialized family of signaling proteins fails as their transport vehicle, a cargo receptor called Wntless (Wls) becomes unstable and is degraded. This important finding provides new insight into what may be a mechanism behind cancer, heart disease or birth defects related to Wnt proteins, researchers said.
Writing for the January 15, 2008 edition of Developmental Cell, researchers at Cincinnati Children’s studied the critical role that a trafficking protein (called Vps35) has as the central assembly platform of the Retromer Complex. This complex is made up of trafficking proteins that act like cellular postmen to return a cargo receptor, Wls, from cellular compartments called endosomes to the Trans-Golgi Network. The network acts like a molecular clearing house - packaging and sorting proteins for targeted delivery - and the job of Wls is to deliver Wnt signaling proteins from Trans Golgi to their intended tissue-building sites. If the Retromer Complex fails to recycle Wls back to the Trans Golgi to do their job, it thwarts stable delivery of Wnt signaling proteins.
“We know secreted Wnt proteins play essential roles in many biological processes, including the development of diseases, but very little is known about the mechanisms by which Wnt processing and secretion are regulated,” said Xinhua Lin, Ph.D., a researcher in the Division of Development Biology at Cincinnati Children’s and senior author of the study. “Our main finding in this study is that the Retromer Complex is required for stable Wnt secretion, providing new insights into how certain diseases work.”
In a series of experiments with genetically engineered cells from the fruit fly Drosophila, mice and humans, Dr. Lin and his colleagues mutated the Vps35 trafficking protein to compromise its central assembly role in the Retromer Complex, then observed the delivery cycle of Wnt proteins between the Trans-Golgi Network and targeted cell sites. In all three series, the compromised Retromer Complex resulted in Wnt protein accumulating in the Trans-Golgi Network and Wls cargo receptors being degraded instead of returning to the network and their job of delivering Wnt proteins.
“Although we propose that the Wls protein acts as a cargo receptor for Wnt signaling proteins, we need to conduct more experiments to further our understanding of this process, including how the Wls delivers Wnt from the Trans-Golgi,” Dr. Lin said.
In their study, the researchers proposed a delivery cycle model where Wnt initially enters the Trans-Golgi Network and binds with the Wls cargo receptor, which then transports Wnt to targeted cell surfaces. Once Wls has delivered Wnt proteins, one of two things occurs, depending on whether the Retromer Complex is functioning normally. When working as designed, the Retromer Complex retrieves the spent Wls protein for return to the Trans-Golgi. When Retromer Complex breaks down, Wls cargo receptor is absorbed into the cell’s lysosome, where it is digested and destroyed.
The study received funding support from partially by grants from the National Institutes of Health, the American Cancer Society, the American Heart Association and the March of Dimes.
Adapted from materials provided by Cincinnati Children’s Hospital Medical Center.

Fausto Intilla
www.oloscience.com

Cannabinoids may suppress tumor invasion in highly invasive cancers. Cannabinoids, the active components in marijuana, are used to reduce the side effects of cancer treatment, such as pain, weight loss, and vomiting, but there is increasing evidence that they may also inhibit tumor cell growth. However, the cellular mechanisms behind this are unknown.

Robert Ramer, Ph.D., and Burkhard Hinz, Ph.D., of the University of Rostock in Germany investigated whether and by what mechanism cannabinoids inhibit tumor cell invasion.

Cannabinoids did suppress tumor cell invasion and stimulated the expression of TIMP-1, an inhibitor of a group of enzymes that are involved in tumor cell invasion.

“To our knowledge, this is the first report of TIMP-1-dependent anti-invasive effects of cannabinoids. This signaling pathway may play an important role in the antimetastatic action of cannabinoids, whose potential therapeutic benefit in the treatment of highly invasive cancers should be addressed in clinical trials,” the authors write.

“Inhibition of Cancer Cell Invasion by Cannabinoids via Increased Expression of Tissue Inhibitor of Matrix Metalloproteinases-1″
Robert Ramer, Burkhard Hinz
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djm268

he Generic Pharmaceutical Association (GPhA) will host its 2008 Annual Meeting, “Generics: the Right Choice for Better Health,” on February 11-13, 2008, in Boca Raton, Florida. Featuring presentations from government, industry and Wall Street leaders, the meeting will examine the current healthcare environment and generics’ critical role in promoting affordable healthcare in the United States.

“As Americans consider their choices for President, Congress and state offices, there is no doubt that health care issues will be top of mind,” said GPhA President and CEO Kathleen Jaeger. “Today, as more Americans delay seeking health care and struggle with paying their bills, they are looking to their elected officials for answers. Increasing access to safe, affordable generics is simply the right choice for obtaining better health care at lower costs, and it is a fitting theme for this year’s meeting.”

Each year, the Annual Meeting brings together CEOs and other top officials from the generic pharmaceutical industry, including manufacturers, distributors, wholesalers, chain drug stores, and health care providers. During the 2008 meeting, participants will hear about the latest industry, legislative and regulatory trends and developments.

The 2008 Annual Meeting will be held at the Boca Raton Resort & Club in Boca Raton, Florida. The meeting kicks off on Monday, February 11 with an evening welcome reception. The plenary sessions and Business Exposition, featuring a diverse array of exhibitors, will be held on February 12-13, beginning with breakfast at 7:30 a.m. The complete agenda will be available in coming weeks.

GPhA represents the manufacturers and distributors of finished generic pharmaceuticals, manufacturers and distributors of bulk active pharmaceutical chemicals, and suppliers of other goods and services to the generic drug industry. Generics represent 63% of the total prescriptions dispensed in the United States, but only 20% of all dollars spent on prescription drugs.

The Generic Pharmaceutical Association
http://www.gphaonline.org

Boston Scientific Corporation (NYSE: BSX) announced that its TAXUS™ Liberté™ paclitaxel-eluting coronary stent system has received European CE Mark approval for use in patients with diabetes.1 Boston Scientific submitted data showing the TAXUS Liberté stent has benefited diabetic patients with coronary artery disease, both in clinical trials and real-world registries. This approval means the TAXUS Liberté stent system now has more CE Mark-approved indications than any other drug-eluting stent, allowing treatment of a wide range of patients including many of those at high risk. The TAXUS Liberté stent system is the most frequently used drug-eluting stent system in Europe.

“Achieving CE Mark approval for TAXUS Liberté in patients with diabetes is an important milestone,” said David McFaul, Boston Scientific Senior Vice President, International. “As a leader in devices for the treatment of cardiovascular disease, Boston Scientific’s goal is to provide patients with the most advanced treatment options available. In this case, we are offering another specific solution for diabetic patients outside the United States, who are typically at higher risk for adverse events compared to non-diabetic patients.”

Combined data from four TAXUS ATLAS trials supported the efficacy and safety of the TAXUS Liberté stent system in diabetic patients.2 The trials examined 1,529 patients treated with the TAXUS Liberté stent system, 413 of whom had diabetes, and reported similar rates of target lesion revascularisation (TLR, or retreatment), cardiac death, myocardial infarction (MI, or heart attack) and stent thrombosis (clotting) between diabetic and non-diabetic stent recipients after adjustment for differences in risk at baseline.

Diabetes affects more than 200 million people worldwide and is expected to affect 360 million people by 2030.3 Approximately half of all patients presenting with coronary artery disease (CAD) in Europe have diabetes.4 Diabetic patients with CAD often have poorer outcomes after revascularisation procedures because their blood vessels tend to build up more plaque than the vessels of non-diabetic patients, and their CAD advances more quickly. CAD is the most common cause of death among European adults with diabetes.5

As a result of the expanded CE Mark, the TAXUS Liberté stent system in the European Union is indicated for treatment of de novo and restenotic lesions or total occlusions in patients with coronary artery disease angina; silent ischaemia; acute myocardial infarction to improve luminal diameter and reduce restenosis within the stent and at the stent edges in native coronary arteries. The TAXUS Liberté stent system is also indicated for patients with concomitant diabetes mellitus as well as treatment of abrupt or threatened closure in patients with failed interventional therapy.

The TAXUS Liberté stent is available outside the United States in a wide range of sizes to treat a diversity of vessel sizes and lesion lengths seen in patients with coronary artery disease.

The TAXUS Liberté stent system is pending approval by the U.S. Food and Drug Administration and is not available for sale in the United States.

Boston Scientific is a worldwide developer, manufacturer and marketer of medical devices whose products are used in a broad range of interventional medical specialties. For more information, please visit: http://www.bostonscientific-international.com.

Otsuka Pharmaceutical Development & Commercialization, Inc. announced recently that the U.S. Food and Drug Administration has accepted a new drug application (NDA) for the company’s investigational oral once-daily medication tolvaptan, a selective V2-vasopressin receptor antagonist, for two indications: treatment of adults with worsening heart failure and treatment of hyponatremia1. These indications are based on data from three phase 3 pivotal trials2.

OPDC was established in 2007 by Otsuka America, Inc. (OAI). OPDC is wholly owned by OAI, which is the holding company for Otsuka Pharmaceutical Co., Ltd. (OPC) interests in the U.S. OAI is wholly owned by OPC.

Tolvaptan is a novel, investigational small molecule designed to be an antagonist of the vasopressin V2 receptor, which plays a role in the kidney’s regulation of fluid excretion. The majority of patients hospitalized for worsening heart failure have edema or excess body fluid, which is treated with diuretics to excrete the fluid. In contrast to diuretics, tolvaptan is designed to promote aquaresis, the excretion of electrolyte-free water. In clinical trials, the most common adverse reactions in patients with worsening heart failure (incidence greater than or equal to 5% in patients treated with tolvaptan and double the incidence of patients treated with placebo) were thirst, dry mouth and polyuria. In patients with hyponatremia, the most common adverse reactions in clinical trials (incidence greater than or equal to 5% in patients treated with tolvaptan and double the incidence of patients treated with placebo) were thirst, dry mouth, asthenia, constipation, pollakiuria and hyperglycemia. The most serious adverse events were cardiogenic shock (1.7% in patients receiving tolvaptan vs. 1.2% of patients receiving placebo), pulmonary embolism (1.3% in patients receiving tolvaptan vs. 0.8% for patients receiving placebo,) and gout (4.7% in patients receiving tolvaptan vs. 3.9% in patients receiving placebo). For all of these, the number of patients that received tolvaptan was 2063 and for placebo was 2055 in addition to standard of care.