Focetria recommended for approval
BASEL, Switzerland
The Committee for Medicinal Products for Human Use (CHMP), which reviews applications for all 27 countries in the European Union, including Iceland and Norway, has recommended approval for the human vaccine Focetria for use in case of an influenza pandemic, such as one that could be caused by the H5N1 virus.
The EU submission for Focetria was considered a "mock-up" since it lays the groundwork for a more rapid approval and availability of a specific vaccine once a pandemic has been declared.
Focetria would be manufactured to contain the pandemic influenza strain declared at the time of a pandemic along with the proprietary adjuvant MF59 developed by Novartis. Studies have shown that MF59 could boost the body's immune response to the vaccine's active constituent and extend vaccine supplies by allowing for smaller amounts of viral antigens to be used in each dose compared with vaccines without this additive.
"The availability of a pandemic influenza vaccine soon after the declaration of a pandemic is essential to reduce disease burden and deaths. This positive recommendation for our proprietary MF59-adjuvanted pandemic vaccine brings us one step closer to achieving public-health and pandemic-preparedness goals," said Dr. Joerg Reinhardt, Novartis chief executive for vaccines and diagnostics.
Novartis submitted the Focetria mock-up file for EU approval in early 2006. In case the World Health Organization declares a pandemic, Novartis will submit a revised application to the European Medicines Agency to incorporate the identified viral strain. This revised application can be approved more quickly than a totally new application. The filing for the Novartis mock-up vaccine was based on clinical studies involving the MF59 adjuvant and different H5N1 strains with pandemic potential.
Separately, Novartis has submitted an MF59-adjuvanted H5N1 prepandemic influenza vaccine for EU approval based on the same technology as Focetria. This vaccine is intended for use prior to a pandemic declaration to help prime and boost the immune system of those receiving the vaccine.
Novartis has engaged in discussions with several governments concerning pandemic-influenza-vaccine supply and has provided H5N1 vaccines for stockpiling, notably in the US and United Kingdom. In January, the US Department of Health and Human Services awarded Novartis a US$55-million contract to further develop the adjuvant technology of MF59 in the US.
Additionally, Novartis has developed a new vaccine-manufacturing process that uses cell cultures rather than chicken eggs for antigen production. The new technology may reduce production time to meet demands of influenza outbreaks and to combat evolving strains of the virus, including avian-influenza strains that are difficult to grow in eggs. The cell-culture-based vaccine Optaflu was submitted for EU regulatory approval in July 2006 and is currently in clinical studies in the US.
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Tekturna, new drug v. hypertension
BASEL, Switzerland
Novartis announced that the United States has become the first country in the world to approve aliskiren (Tekturna), the first new type of medicine in more than a decade for treating high blood pressure, which affects nearly one billion people worldwide and remains uncontrolled in nearly 70 percent of patients.
The US Food and Drug Administration (FDA) issued the approval for Tekturna as the first in a new class of drugs called direct renin inhibitors. A once-daily oral drug, Tekturna acts by targeting renin-an enzyme responsible for triggering a process that can contribute to hypertension, a key contributor to cardiovascular disease, which remains the world's leading cause of death.
Tekturna received FDA approval for treatment of hypertension as monotherapy or in combination with other antihypertensive medications. Tekturna is will be available in the US starting March in 150-mg and 300-mg tablets.
"Renin-angiotensin-system activity contributes to many of the complications associated with high blood pressure," said Dr. Marc professor of medicine at the Harvard Medical School and cardiologist at Brigham and Women's Hospital. "By inhibiting this important system at its origin, renin production, a direct renin inhibitor such as Tekturna offers an exciting novel therapeutic option for treating hypertension."
In an extensive clinical trial involving more than 6,400 patients, Tekturna provided significant blood-pressure reductions for a full 24 hours. It also provided added efficacy when used in combination with other commonly used blood-pressure medicines. In clinical trials, the approved doses of Tekturna were generally well tolerated.
"Many patients require two or more medicines to control their blood pressure. As a new treatment approach, Tekturna has the potential to help these patients manage their disease," said Dr. James Shannon, global head of development at Novartis Pharma AG. "Tekturna demonstrates our commitment to developing innovative medicines to help the millions of patients suffering from high blood pressure."
Novartis is committed to conducting a large outcome-trial program to evaluate the long-term effects of Tekturna and direct renin inhibition.
In September 2006, Tekturna, which will be known as Rasilez outside the US, was submitted to the European Medicines Agency for review in the European Union. Tekturna was developed in collaboration with Speedel.
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Tykerb shows promise v. cancer
GlaxoSmithKline (GSK) said results from a large, randomized, phase-III study showed that the combination of lapatinib ditosylate (Tykerb) and capecitabine (Xeloda) versus capecitabine alone nearly doubled the time to progression of metastatic ErbB2-positive breast cancer in patients whose disease had progressed following treatment with trastuzumab (Herceptin) and other therapies. The time to progression was 36.9 weeks in the combination arm versus 19.7 weeks with capecitabine monotherapy.
"Because ErbB2-positive breast cancer may eventually progress during or following treatment with trastuzumab, there has been a need for an effective alternative treatment that can successfully block the function of ErbB2 in another way," said principal investigator Dr. Charles Geyer of the Allegheny General Hospital in Pittsburgh, Pennsylvania. "These results indicate that lapatinib can provide a needed alternative when trastuzumab no longer appears to be helping to control the disease."
Tykerb, a small molecule administered orally, inhibits the tyrosine-kinase components of ErbB1 and ErbB2 receptors. Stimulation of ErbB1 and ErbB2 is associated with cell proliferation and with multiple processes involved in tumor progression, invasion, and metastases. Overexpression of these receptors is associated with poor prognosis and reduced overall survival.
"These results suggest that Tykerb has significant potential as an essential component of the treatment regimen for women with advanced breast cancer," said Dr. Paolo Paoletti, senior vice president for oncology-medicine development at GSK.
The international, multicenter, open-label study (EGF100151) enrolled 392 patients who had advanced or metastatic breast cancer with documented ErbB2 overexpression and whose disease had progressed following treatment with trastuzumab and other cancer therapies. The interim analysis included 321 patients (160 in the Tykerb-capecitabine arm and 161 in the capecitabine monotherapy arm).
Another study provided preliminary evidence suggesting that Tykerb may be effective in treating brain metastases associated with breast cancer. The phase-II trial evaluated Tykerb in 39 patients with ErbB2-positive breast cancer who had developed CNS metastases while on trastuzumab. Two patients achieved partial response as measured by RECIST, a linear measure of solid tumors. Five patients achieved stable disease for 16 weeks or more. Volumetric analysis, a more precise three-dimensional measure of tumor volume performed in 20 patients, showed five of the patients with at least a 30-percent decline in CNS lesions and three with 15- to 30-percent decline.
Tykerb is being developed by GSK as an orally administered therapy for breast cancer and other solid tumors. The compound already has been granted fast-track status by the United States Food and Drug Administration for the treatment of refractory advanced or metastatic breast cancer in women who have documented ErbB2 overexpression and who have failed previous therapy.
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Crestor reverses atherosclerosis
A study has shown that intensive treatment with rosuvastatin (Crestor) leads to regression of coronary-atheroma volume among patients with coronary-artery disease. The findings demonstrate for the first time that reduction of more than 40 percent in levels of low-density lipoproteins (LDL) can not only delay the progression of atherosclerosis but translate to regression of the atheroma burden.
Previous studies have established that progress can be delayed and even halted, but regression has never been convincingly documented. Coronary-angiography studies showed that a 40-percent reduction in LDL levels is necessary to delay progress of arterial stenosis.
"So far, [rosuvastatin] has … the highest reduction in LDL level among all major trials of statins, and in addition to the 53-percent reduction in LDL, there is a significant bonus of about 15-percent increase in good cholesterol," said cardiologist John Añonuevo at the recent 12th joint annual convention of the Philippine Society of Hypertension and the Philippine Lipid and Atherosclerosis Society. "This is a very good combination of a very marked decrease in LDL and a significant increase in HDL," said Añonuevo, who presented the findings of ASTEROID-A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary-Atheroma Burden.
ASTEROID showed that the improvements in lipid profile corresponded to significant reductions in atheroma volumes, measured by ultrasound. By the end of the study period, those given rosuvastatin achieved 0.79-percent reduction in atheroma volume. This makes ASTEROID "the first trial among statins to have documented a significant regression in coronary artery disease," said Añonuevo.
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Ancrod for stroke treatment
PARIS
Ancrod, an anticlotting drug derived from the venom of Malaysian pit vipers, is only effective in treating stroke victims if given within three hours, according to a study in The Lancet.
European doctors assessed ancrod, when administered within six hours of a stroke among 1,220 patients in Europe, Australia, and Israel. No significant benefit was found when the drug was administered beyond three hours, according to the paper. It also highlighted risks of hemorrhage and problems with neurological recovery among the ancrod group compared with the placebo group.
Ancrod, branded as Arwin and Viprinex, is an anticoagulant, intended to thin blood viscosity in arteries affected by ischemic stroke, thus helping to ease pain, improve limb mobility, and combat the risk of localized blood clots. M AFP
Herceptin boosts survival chances
PARIS
Trastuzumab (Herceptin) can boost early survival chances when used after standard chemotherapy to tackle a notoriously aggressive form of early breast cancer, a new study says.
Herceptin, marketed by Genentech and Roche, is an engineered antibody that adheres to the so-called HER-2 protein on the tumor cell's surface. It blocks instructions for the cell to divide and signals to immune cells to destroy the tumor cell.
Around a fifth of women with early-stage breast cancer have a type called HER-2 positive, which is swiftly invasive and leaves only a meager hope of survival.
Doctors led by Ian Smith of the Royal Marsden Hospital in London tested Herceptin as an adjuvant treatment among women with early-stage HER-2 positive cancer. More than 1,700 women received Herceptin for one year after surgery and chemotherapy, while 1,698 others who also had surgery and chemotherapy were allocated to a comparison group but did not receive the drug.
Fifty-nine women in the Herceptin group died three years after surgery, while 90 died in the "control" group. Taking Herceptin was roughly equivalent to saving one additional woman for every 55 treated. But there were 10 cases of severe congestive heart failure in the Herceptin group-a problem identified in previous studies.
Because HER-2-positive cancers move so quickly, early action is vital, which is why Herceptin is now being tested on patients with the disease in its early stages. Herceptin has already received approval in key markets for treating HER-2 cancer in its advanced stages.
In 2005, two US trials found that, when used with chemotherapy, Herceptin reduced the risk of early death or recurrence of early-stage cancer by 52 percent at the two-year mark. That research sparked headlines that a wonder drug had been found for the curse of breast cancer. But it also stirred some controversy.
Experts wrangled as to whether Herceptin's apparent benefits outweighed the risks of cardiac damage, stressing that the long-term impact remained unclear. Another question is cost-effectiveness. A one-year course of Herceptin costs around US$30,000 a year. This has pitched breast-cancer activists against other groups as to whether scarce health funds should be allocated for buying the costly drug or devoted to other problems.
The new study appears in The Lancet, alongside a commentary which cautions that some questions about Herception remain unresolved.
M AFP
GSK files Cervarix application
PHILADELPHIA
GlaxoSmithKline (GSK) has submitted a license application for Cervarix (human papillomavirus vaccine, AS04 adjuvant-adsorbed) to the United States Food and Drug Administration (FDA). If licensed, the vaccine will be indicated for the prevention of cervical cancer and precancerous lesions associated with the most common cancer-causing human papillomavirus types.
For this candidate vaccine, GSK selected a novel proprietary adjuvant system called AS04, intended to enhance immune response and increase duration of protection. Published data have shown that the vaccine formulated with AS04 provides a stronger and longer-lasting immune response compared with the same vaccine composition formulated with a traditional aluminum hydroxide adjuvant.
The license application includes data from clinical trials involving an ethnically diverse group of almost 30,000 females 10 to 55 years old. It also contains data from the largest phase-III cervical-cancer-vaccine efficacy trial conducted around the world in more than 18,000 females 15 to 25 years of age.
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Insomnia drug to phase-III trial
The Netherlands
Organon has moved Org 50081, a serotonin 2 blocker (S2B) for the treatment of insomnia, into phase-III clinical development.
Willem de Laat, executive vice president for medical affairs at Organon, said: "Investigated dosages of the Org 50081 compound showed positive and robust results on multiple sleep parameters such as total sleep time and wakefulness after sleep onset. A statistically significant shorter time to sleep onset was demonstrated in Org 50081 treatment groups compared to placebo."
The serotonin-2 blockade of Org 50081 is unique for an insomnia drug. Unlike most other insomnia drugs, which work by interacting with the GABA receptors and thus have a potential risk for dependency, Org 50081's action is on the serotonergic and histaminergic systems. As such, while Org 50081 may improve both sleep initiation and sleep maintenance it is not likely to cause dependency.
"Patients who suffer from insomnia need to have a treatment without addictive properties. A treatment such as Org 50081 could help the patients tremendously if it proves successful in phase III." said Toon Wilderbeek, the Akzo Nobel board member responsible for pharma.
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