H1N1 swine flu may be fading from the news some, but the number of confirmed cases nationwide has been higher than is usual for seasonal flu in the month of May. What does that mean? Is this flu’s ability to linger into the spring suggestive of how different a beast it is? And what does it portend for how the virus might infect Americans over the summer and come fall?

The Centers for Disease Control and Prevention publishes confirmed cases of the novel H1N1 swine flu virus each week. The official count of probable cases in the U.S. as of Friday was 8,975 in 49 states with 15 deaths. However, the total number of people infected in the country is estimated to be as high as 100,000, says CDC spokesman Joe Quimby, taking into account those who were sick but didn’t seek medical care.

For the most part, the H1N1 virus doesn’t act very differently from our contemporary flu strains in terms of how sick people get and how easily it is transmitted from person to person, says Ira Longini, an expert in modeling the spread of infectious disease. Its lingering presence in the spring is probably because nearly the entire human population is susceptible to infection with it.

“Usually, we have some protection, even [in] children, due to past illness or vaccination,” Longini says. But with swine flu, that’s not the case. “So it’s going to spread very easily when it’s introduced into families and schools,” causing sickness even at a time outside of the flu’s normal season.

Merely an omen?

Why seasonal flu winds down every spring is not entirely clear, but contributing factors may include a change in climate — flu viruses survive longer in cooler, drier air — and a dwindling number of susceptible people. The spread of swine flu may be interrupted by warmer weather and by schools letting out for summer.

Or it may not. “When you have a highly transmissible, immunologically novel virus, you can have widespread epidemics throughout summer,” says Don Olson, research director at the nonprofit International Society for Disease Surveillance in New York. “Our population level of immunity is just poor enough that we’re kind of like dry wood.”

In 1957, for example, there were summer outbreaks of the so-called Asian flu that would later become a pandemic and cause nearly 70,000 U.S. deaths. Several outbreaks were well-documented and included a church gathering of international students in Grinnell, Iowa, and schoolchildren in Louisiana, who were attending school in August that year.

Also, the 1957 pandemic started in earnest in September, much earlier than is normal for seasonal flu.

“Pandemic influenza is not the same as seasonal influenza. It doesn’t respect seasonality the same way,” says Lone Simonsen, a flu expert at George Washington University in Washington, D.C.

Scientists think the spring swine flu epidemic may be a “herald wave” of what’s to come. In 1918, a milder wave of flu cases occurred in late winter and early spring, before the deadly pandemic surge in the fall of that year. In 1957, Asian flu was causing unremarkable illness in China, before landing on American soil for the summer outbreaks and a severe winter season.

Simonsen has studied past pandemics and says that a pattern of multiple waves is common to all of them also. The 1957 pandemic flu had three waves in the U.S. over five years, with a large number of deaths in the winters of 1959 and 1962. The 1968 pandemic flu had two waves in the British Isles over consecutive years, with 15% of the total number of deaths occurring in winter 1968 and the remaining 85% in winter 1969.

No way to predict

Another common feature of past flu pandemics is the age groups of the victims. The CDC says that seasonal flu contributes to some 36,000 deaths in the U.S. each year and 90% of those are senior citizens 65 or older. History has shown flu pandemics killing higher proportions of younger adults. One reason might be that older people, with more years’ exposure to many strains of flu virus, have some immunity against an emerging virus.

But researchers are in agreement on this: No one can predict the future of 2009 swine flu with certainty.

“The prediction is really difficult. We can say that certain features that are always true for pandemics. Then there are things that just vary,” Simonsen says.

“That’s just how it is.”

A 42-year-old HIV patient with leukemia appears to have no detectable HIV in his blood and no symptoms after a stem cell transplant from a donor carrying a gene mutation that confers natural resistance to the virus that causes AIDS, according to a report published Wednesday in the New England Journal of Medicine.

“The patient is fine,” said Dr. Gero Hutter of Charite Universitatsmedizin Berlin in Germany. “Today, two years after his transplantation, he is still without any signs of HIV disease and without antiretroviral medication.”

The case was first reported in November, and the new report is the first official publication of the case in a medical journal. Hutter and a team of medical professionals performed the stem cell transplant on the patient, an American living in Germany, to treat the man’s leukemia, not the HIV itself.

However, the team deliberately chose a compatible donor who has a naturally occurring gene mutation that confers resistance to HIV. The mutation cripples a receptor known as CCR5, which is normally found on the surface of T cells, the type of immune system cells attacked by HIV.

The mutation is known as CCR5 delta32 and is found in 1 percent to 3 percent of white populations of European descent.

HIV uses the CCR5 as a co-receptor (in addition to CD4 receptors) to latch on to and ultimately destroy immune system cells. Since the virus can’t gain a foothold on cells that lack CCR5, people who have the mutation have natural protection. (There are other, less common HIV strains that use different co-receptors.)

People who inherit one copy of CCR5 delta32 take longer to get sick or develop AIDS if infected with HIV. People with two copies (one from each parent) may not become infected at all. The stem cell donor had two copies.

While promising, the treatment is unlikely to help the vast majority of people infected with HIV, said Dr. Jay Levy, a professor at the University of California San Francisco, who wrote an editorial accompanying the study. A stem cell transplant is too extreme and too dangerous to be used as a routine treatment, he said.

“About a third of the people die [during such transplants], so it’s just too much of a risk,” Levy said. To perform a stem cell transplant, doctors intentionally destroy a patient’s immune system, leaving the patient vulnerable to infection, and then reintroduce a donor’s stem cells (which are from either bone marrow or blood) in an effort to establish a new, healthy immune system.

Levy also said it’s unlikely that the transplant truly cured the patient in this study. HIV can infect many other types of cells and may be hiding out in the patient’s body to resurface at a later time, he said.

“This type of virus can infect macrophages (another type of white blood cell that expresses CCR5) and other cells, like the brain cells, and it could live a lifetime. But if it can’t spread, you never see it– but it’s there and it could do some damage,” he said. “It’s not the kind of approach that you could say, ‘I’ve cured you.’ I’ve eliminated the virus from your body.”

Before undergoing the transplant, the patient was also found to be infected with low levels of a type of HIV known as X4, which does not use the CCR5 receptor to infect cells. So it would seem that this virus would still be able to grow and damage immune cells in his body. However, following the transplant, signs of leukemia and HIV were absent.

“There is no really conclusive explanation why we didn’t observe any rebound of HIV,” Hutter said. “This finding is very surprising.”

Hutter noted that one year ago, the patient had a relapse of leukemia and a second transplant from the same donor. The patient experienced complications from the procedure, including temporary liver problems and kidney failure, but they were not unusual and may occur in HIV-negative patients, he said.

Researchers including Hutter agree that the technique should not be used to treat HIV alone. “Some people may say, ‘I want to do it,’” said Levy. A more logical — and potentially safer — approach would be to develop some type of CCR5-disabling gene therapy or treatment that could be directly injected into the body, said Levy.

Less invasive options to alter CCR5 could be on the horizon within the next five years, said Levy. “It’s definitely the wave of the future,” he said. “As we continue to follow this one patient, we will learn a lot.”

One drug that’s currently on the market that blocks CCR5 is called maraviroc (Selzentry). It was first approved in 2007 and is used in combination with other antiretroviral drugs.

In 2007, an estimated 2 million people died from AIDS, and 2.7 million people contracted HIV. More than 15 million women are infected worldwide. HIV/AIDS can be transmitted through sexual intercourse, sharing needles, pregnancy, breast-feeding, and/or blood transfusions with an infected person.

“For HIV patients, this report is an important flicker of hope that antiretroviral therapy like HAART [highly active antiretroviral therapy] is not the endpoint of medical research,” Hutter said.

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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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.