CELATOR® PHARMACEUTICALS PRESENTS PHASE 1 RESULTS WITH
CPX-351 IN PATIENTS WITH ADVANCED LEUKEMIA AT THE AMERICAN SOCIETY OF HEMATOLOGY MEETING

Findings confirm advantages of fixed-ratio drug delivery and lay the groundwork for Phase 2 trials already underway in first-line and first-relapse Acute Myeloid Leukemia (AML) settings

Today Celator Pharmaceuticals announced that a Phase 1 dose escalating study of CPX-351 (cytarabine:daunorubicin) Liposome Injection established the recommended dose for Phase 2 studies and confirmed preliminary observations of safety, enhanced pharmacokinetics and promising anti-tumor activity in patients with advanced leukemia. A final analysis of the Phase 1 data (abstract #2984) and supportive findings from a pre-clinical pharmacodynamic model (abstract #942) were presented at the 50th American Society of Hematology (ASH) Annual Meeting in San Francisco.

“In the Phase 1 trial, CPX-351 had a tolerability profile that appears better than conventional cytarabine/daunorubicin treatment and produced impressive anti-leukemic responses, including complete remissions (CRs) at and below the maximum tolerated dose, in relapsed and refractory patients,” said Eric J. Feldman, MD, of the Weill Medical College of Cornell University and New York-Presbyterian Hospital, the principal investigator in the study. “These encouraging results suggest that CPX-351 may offer advantages to conventional administration of these commonly used drugs. We are excited to participate in the two Phase 2 studies.”

In the study, complete remissions were observed in 11 of 47 patients, including 10 patients (9 CRs and 1 CRp - complete remission without full platelet recovery) of 44 with AML and 1 patient of 3 with acute lymphocytic leukemia (ALL) following treatment with CPX-351. Of the 10 AML CRs, 7 occurred at the two highest dose levels, although complete remissions were achieved at dose levels as little as one third of the maximum tolerated dose (MTD). Of note, 7 CRs were achieved in 22 patients in the 1st salvage setting (patients in first relapse or with refractory disease) and 3 CRs were achieved in 22 patients in the 2nd or greater salvage settings. In addition, CRs were observed in patients older than 70 years, in those with complex cytogenetic abnormalities, and in patients with prior cytarabine/anthracycline treatment.

“The standard of care for AML hasn’t changed in 30 years and there is an urgent need to improve treatment for both newly diagnosed and relapsed patients,” said Arthur Louie, MD, chief medical officer at Celator Pharmaceuticals. “We began enrolling patients in a Phase 2 study in newly diagnosed, elderly patients with AML and we expect to start enrollment soon in a Phase 2 study in patients with AML in first relapse.”

CPX-351 represents a new approach to developing drug combinations in which drug molar ratios with synergistic anti-tumor activity are encapsulated in a drug delivery vehicle and the desired ratio is maintained following administration using Celator’s proprietary CombiPlex® technology platform. CPX-351 has been granted orphan drug status by the U.S. Food & Drug Administration for the treatment of AML.

“CPX-351 incorporates two of the most active agents against AML in a manner that, as we’ve shown in this study, maintains ratio-dependent synergy after administration,” said Scott Jackson, chief executive officer, Celator Pharmaceuticals. “We believe this unique capability has the potential to improve treatment outcomes for patients and we are looking to our randomized Phase 2 trials for proof of this principle.”

The safety profile of CPX-351 observed in the study was considered favorable. The most frequent and severe adverse events were those related to potential or documented infections including fever, febrile neutropenia, bacteremia, pneumonia and sepsis, common occurrences in the treatment of patients with AML. Although, mortality related to treatment is normally an issue when treating AML patients, there were no deaths within 7 days of treatment and 6 deaths (13%) within 30 days of receiving CPX-351. The induction mortality seen in the Phase 1 study was deemed encouraging by investigators. Major GI toxicity was uncommon with only 4 patients experiencing grade 3 or greater nausea and vomiting or mucositis.

Pharmacokinetic data collected during the study confirmed the bioavailability of cytarabine and daunorubicin, demonstrated a prolonged half-life for both drugs and their metabolites, and confirmed that the synergistic ratio was maintained for more than 24 hours after infusion.

The Phase 1 study enrolled 37 patients with advanced AML, secondary AML and ALL, during the dose-escalation phase. The maximum tolerated dose was established at 101 units/m2. An additional 10 patients were recruited and treated at this dose level to confirm tolerability and collect preliminary data on efficacy, bringing the total trial enrollment to 47. The recommended dose for Phase 2 study was determined to be 101 units/m2 given as a 90 minute infusion on treatment days 1, 3, and 5.

These findings were supported by a separate pre-clinical study that was also reported at the ASH meeting. Using a bone marrow engrafted human leukemia xenograft model, investigators compared CPX-351 with conventional cytarabine/daunorubicin treatment. The study confirmed that CPX-351, unlike the conventional combination, produced prolonged exposure of CPX-351 in the bone marrow and evidence of direct uptake of CPX-351 by leukemia cells with subsequent intracellular release of the drugs. Exposure of leukemic cells to synergistic drug ratios was confirmed.

In November, Celator announced enrollment of the first patient in a randomized Phase 2 study of CPX-351 versus conventional cytarabine and daunorubicin (”7 + 3″) in patients with newly diagnosed AML, between 60 and 76 years of age. A second Phase 2 study of CPX-351 in patients 18-60 years old with AML in first relapse is also being initiated.

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Pfizer announced the results of an observational study that showed patients taking Lipitor® (atorvastatin calcium) had a significant 13 percent reduction in the relative risk of experiencing a cardiovascular event compared with patients taking simvastatin (Zocor®) therapy. The patients in this study did not have evident cardiovascular disease and were newly initiated on either treatment. This study was performed in conjunction with HealthCore, WellPoint’s health outcomes research subsidiary. Results of this study, from one of the largest U.S. managed care claims databases with more than 219,000 adult patients, were published in the December issue of Mayo Clinic Proceedings.

The study examined data for patients 18-64 years old who had no prior statin use or medical claims related to cardiovascular disease in the 12 months preceding initiation of statin therapy. The average doses in the study were 29 mg of simvastatin and 17 mg of Lipitor.

“Observational data such as this, which reflect the use of medicines in real-world clinical practice rather than in a controlled trial setting, may help healthcare providers and managed care companies improve clinical outcomes for patients,” said Terry A. Jacobson, Professor of Medicine, Emory University, and director of the Office of Health Promotion and Disease Prevention, Grady Health Systems. “The data suggests that statins with greater potency may result in greater cardiovascular risk reductions. Economic assessments should be performed to determine the potential impact of this study on cost of care to patients.”

In addition to the significant reduction in the risk of overall cardiovascular events, individual event rates of secondary endpoints, first heart attack and hospitalizations for heart failure, were significantly lower for patients initiating Lipitor compared with patients initiating simvastatin. There was no significant difference between the groups for the secondary endpoints of stroke, revascularization surgery or peripheral vascular disease.

“This latest analysis adds to the wealth of real-world data from a number of different medical database analyses that suggest that patients who are treated with Lipitor may have a reduced risk of experiencing a cardiovascular event compared with patients who use simvastatin,” said Dr. Michael Berelowitz, senior vice president of Pfizer’s global medical division. “Findings such as these should be taken into account by those who may assume that medicines in a therapeutic class are interchangeable and provide similar outcomes.”

As with all observational studies, the study is subject to certain limitations and the findings should be regarded as hypothesis generating.

About the study

This is one of the largest observational studies to date to examine cardiovascular outcomes in patients without clinically evident cardiovascular disease treated with different statins in routine clinical practice.

The retrospective analysis examined administrative claims for statin prescriptions filed between January, 2003 and December, 2005. The longer mean treatment duration of patients who took Lipitor versus simvastatin (nine and seven months, respectively) might have impacted the difference in cardiovascular event reduction.

A cardiovascular event was defined as the first inpatient or emergency room admission for heart disease, heart attack, angina (chest pain), certain heart surgeries, peripheral vascular disease, aortic aneurysm (swelling of the aorta), stroke and transient ischemic attack.

Since patients were not randomly assigned to each group, the two treatment arms were adjusted based on certain risk factors, such as age, gender and co-morbidities, and statistical adjustments were used to address residual imbalances. LDL values prior to and after treatment were only available for approximately five percent of the patients and this was not adjusted for in the analysis.

The results of this study complement the large body of evidence from multiple clinical trials demonstrating the cardiovascular benefits of Lipitor in patients without heart disease and are in alignment with findings from previously published observational studies.

Important U.S. Prescribing Information

Lipitor is a prescription medication. It is used in patients with multiple risk factors for heart disease such as family history, high blood pressure, age, low HDL (“good” cholesterol) or smoking to reduce the risk of a heart attack, stroke, certain types of heart surgery and chest pain.

Lipitor is also used in patients with type 2 diabetes and at least one other risk factor for heart disease such as high blood pressure, smoking or complications of diabetes, including eye disease and protein in urine, to reduce the risk of heart attack and stroke.

Lipitor is used in patients with existing coronary heart disease to reduce the risk of heart attack, stroke, certain kinds of heart surgery, hospitalization for heart failure, and chest pain.

When diet and exercise alone are not enough, Lipitor is used along with a low-fat diet and exercise to lower cholesterol.

Lipitor is not for everyone. It is not for those with liver problems. And it is not for women who are nursing, pregnant or may become pregnant.

Patients taking Lipitor should tell their doctors if they feel any new muscle pain or weakness. This could be a sign of rare but serious muscle side effects. Patients should tell their doctors about all medications they take. This may help avoid serious drug interactions. Doctors should do blood tests to check liver function before and during treatment and may adjust the dose. The most common side effects are gas, constipation, stomach pain and heartburn. They tend to be mild and often go away.

In Friday shares of Sunrise Assisted Living (SRZ) jumped 74 % to $ 0.99. But shares of Sunrise Assisted Living worth $ 31.98 year ago.

In Friday Sunrise Senior Living announced the receipt of approximately $8.3 million of proceeds resulting from the refinancing of the existing debt of one of its joint ventures.
As disclosed yesterday by Ventas, Inc., a venture owned 85 percent by Ventas and 15 percent by Sunrise closed eight first-mortgage loans with Freddie Mac, secured by eight senior housing communities managed by Sunrise, aggregating $126 million. Proceeds of the new $126 million Freddie Mac loan were used to repay in full $71 million of existing debt of the venture which was secured by the same eight assisted living communities and was scheduled to mature in mid-2009. The balance of the new loan proceeds was distributed pro-rata to Ventas and Sunrise, with Sunrise’s portion totaling approximately $8.3 million.
“We are pleased that Freddie Mac recognized the strength of this portfolio of our core management product in this difficult economic environment,” said Mark Ordan, Sunrise’s chief executive officer.
On a preliminary basis, Sunrise expects to recognize approximately $8.3 million in equity in earnings as a result of this transaction in the fourth quarter.

About Sunrise Senior Living
Sunrise Senior Living, a McLean, Va.-based company, employs approximately 40,000 people. As of September 30, 2008, Sunrise operated 448 communities in the United States, Canada, Germany and the United Kingdom, with a combined capacity for approximately 55,000 residents. At quarter end, Sunrise also had 34 communities under construction in these countries with a combined capacity for 4,277 additional residents. Sunrise offers a full range of personalized senior living services, including independent living, assisted living, care for individuals with Alzheimer’s and other forms of memory loss, as well as nursing, rehabilitative and hospice care. Sunrise’s senior living services are delivered by staff trained to encourage the independence, preserve the dignity, enable freedom of choice and protect the privacy of residents.