Researchers used the placebo effect to successfully treat psoriasis patients with one quarter to one half of their usual dose of a widely used steroid medication, according to an early study published online today in the journal Psychosomatic Medicine. Early results in human patients suggest that the new technique could improve treatment for several chronic diseases that involve mental state or the immune system, including multiple sclerosis and chronic pain.

By designing treatment regimens that mix active drug and placebo, researchers at the University of Rochester Medical Center hope to maximize drug benefits, reduce side effects, increase the number of patients who take their medicine and extend the use of drugs otherwise limited by addiction risk or toxicity. Using a fraction of the usual drug dose to get the same effect could also make possible a dramatic and timely reduction in healthcare costs, according to the authors.

The publication is a product of decades of research in the emerging field of “psychoneuro-immunology,” which holds that the ability of the human immune system to fight disease is closely linked with a person’s mind. Thoughts and moods are captured in neurochemicals that cause the release of hormones which interact with disease-fighting cells.

The current research team chose psoriasis for their first human experiments because it is chronic, gets worse when patients feel stress and involves the immune system. The condition causes pain and disability in four million Americans as inherited traits and irritants cause the immune system to trigger the too fast production of skin cells, resulting in red, scaly patches of dead skin.

“Our study provides evidence that the placebo effect can make possible the treatment of psoriasis with an amount of drug that should be too small to work,” said Robert Ader, Ph.D., M.D. (hc), distinguished university professor in the University of Rochester School of Medicine & Dentistry. “While these results are preliminary, we believe the medical establishment needs to recognize the mind’s reaction to medication as a powerful part of many drug effects, and start taking advantage of it,” said Ader, professor of Psychiatry and principal investigator of the study. The placebo effect, obviously, cannot help unconscious patients, or replace substances that the body itself is unable to produce, he added. In the absence of functioning islet cells, for example, placebos cannot stimulate the release of insulin in a Type l diabetic.

Study Details

A description of the current findings requires expanding the definition of placebo effects to include phenomena that are not fully understood by modern medicine, Ader said. Although placebos, “dummy pills” that have no therapeutic effect by themselves, are prescribed by many physicians today, their use still carries a stigma. It’s as if the effect of a pill containing no medication is not “real,” part magic and part deception.

To accurately define and study the placebo effect, Ader and colleagues chose to frame it as an example of a well-established psychological phenomenon: the conditioned response. Nineteenth century Russian physiologist Ivan Pavlov was the first to study the phenomenon of conditioning. By ringing a bell (a conditioned stimulus) each day before giving his dogs food (an unconditioned stimulus), Pavlov found that the dogs would eventually salivate (a conditioned response) at the sound of the bell alone.

In the current study, Ader and colleagues sought to determine if a drug’s therapeutic effect could be triggered by qualities associated with the drug, like its shape, color, smell and packaging, as well as by its administration by an authority figure in a white lab coat. These repeated associations, Ader argues, create conditioned responses, drug-like therapeutic effects of treatment caused, not by a drug’s ingredients alone, but elicited by stimuli associated with the effects of active drug treatment. The results provide the first evidence that conditioned responses might be harnessed to influence the design of drug regimens in humans.

Research teams at the University of Rochester Medical Center and Stanford University conducted an 11 to 14-week, double-blind, randomized clinical trial in 46 patients with mild-to-moderate psoriasis. Patients were on no other medications during the study, and had signed consent forms after being informed they might receive a reduced dose of topical steroid.

At the start of the study, researchers randomly selected two “target” psoriatic lesions or sores on each patient. Twice each day during a three-week baseline period, all patients spread a lotion containing a full dose of steroid medication (0.1% Aristocort A, triamcinolone acetonide) onto one of their two study lesions. The second lesion was coated with a moisturizing cream. Medicated and unmedicated creams were distributed in coded syringes to make them indistinguishable.

Nearly all past drug studies divided patients into two groups only. One would get the full dose of the drug all of the time (a 100 percent reinforcement schedule). The other would get zero drug all of the time (zero percent reinforcement). The current study asks for the first time: what if we treat patients with something in between drug and placebo? After the three-week baseline period, patients were randomly assigned to one of three groups.

The first continued to receive 100 percent of the treatment drug at each administration for the rest of the study on his or her study lesion. A second, the partial reinforcement group, also continued to receive a full dose, but only 25 or 50 percent of the time, and a steroid-free emollient the rest of the time. The study was designed so that this second group could benefit from exposure to cues they had previously associated with active drug treatment (a conditioned therapeutic effect). A third group, the “dose control group,” received active drug at every administration, but at 25 or 50 percent of the full dose used in the first and second groups. Thus, the partial reinforcement and “dose control” groups received the same total amount of active medication, but in different patterns.

Results were measured in two ways. First, a “blinded” dermatologist measured the severity of a patient’s psoriasis lesions weekly using the Psoriasis Severity Scale (PSS), a standard tool used to track the redness, hardening and thickening of skin. The second measure was whether a patient experienced a “relapse” in lesion severity, defined arbitrarily as a return to a PSS score within two units of a patient’s initial score.

In terms of the overall PSS severity scores, results were mixed. The Stanford study site found no group differences in PSS scores that could be attributed to the different treatment regimens. Ader believes that elevated baseline PSS scores in the randomly selected Dose Control subjects at Stanford might have obscured the differences between the dose control and partial reinforcement groups. For instance, results could have been influenced by differences in the amount of sun patients were exposed to in Upstate New York and California (ultraviolet light is an established treatment for psoriasis).

In Rochester, there were no differences between the PSS values of the Partial Reinforcement and Dose Control groups at the point in the study where experimental treatment began. In this case, partial reinforcement brought about a greater reduction in lesion severity during the experimental period than continuous reinforcement (dose control) with the same cumulative amount of drug.

The relapse results were clearer. Four of 18 patients (22.2 percent) in the 100 percent reinforcement group (full dose all the time) relapsed within the eight-week experimental period. Among patients treated with a full dose of drug, but one half or one quarter of the time (50 or 25 percent reinforcement schedule), four of 15 patients (26.7 percent) relapsed. Thus, the incidence of relapse did not differ substantially between patients receiving a full dose of drug all the time and those treated under the partial reinforcement schedules, researchers said. In contrast, eight of the 13 patients (61.5 percent) in the dose control group who received active drug each time, but not the full does, relapsed in the same period of time.

Thus, the incidence of relapse in the partial reinforcement group (26.7 percent) was significantly less than in dose control patients (61.5 percent) that received the same cumulative amount of drug. Further studies are underway, and others are planned, to confirm the effect, answer the questions raised and explore the effect in other autoimmune diseases.

The study was conducted jointly by the Departments of Psychiatry and Dermatology within the School of Medicine & Dentistry at the University of Rochester and the Stanford University School of Medicine. Along with Ader, the study was authored in Rochester by Mary Gail Mercurio, James Walton and Deborra James. Leading the effort at Stanford were David Fiorentino, Alexa Kimball, Michael Davis and Valerie Ojha. The study was funded by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of the National Institutes of Health (NIH).

“The pharmaceutical industry may choose to ignore the conditioning component of drug treatment regimens,” Ader said. “Alternatively, they may now consider exploring ways to exploit conditioning in the design of drug treatment protocols, especially in chronic conditions where patients acquire conditioned responses over time. I believe industry will eventually support this approach because it promises to increase safety and reduce production costs.”

Source: University of Rochester Medical Center

Magnetic stimulation therapy can beat depression when medication and therapy haven’t worked, according to the December issue of Mayo Clinic Health Letter.

The therapy, called transcranial magnetic stimulation (TMS), involves using brief powerful electromagnetic pulses to alter brain activity. The U.S. Food and Drug Administration (FDA) has approved the therapy for patients whose depression hasn’t improved with medications — estimated to be from 10 to 20 percent of those with the illness.

Patients treated with TMS may experience total remission of depression symptoms. A 50 percent improvement in depression symptoms is common.

A typical treatment schedule involves five, one-hour sessions a week for at least three to five weeks. During a session, the patient sits in a reclining chair while the magnetic coil is positioned and activated. Patients remain awake and alert as the coil alters brain activity. No anesthesia or invasive procedures are used. The benefits gradually emerge over several weeks.

A recent study compared TMS therapy in a group of people who had drug-resistant depression to a matched group of patients who received an inactive placebo form of TMS therapy. After four to six weeks, the TMS group was twice as likely to have remission of depression symptoms as the group receiving the placebo treatment.

While TMS is being used to treat depression at select medical centers, there are still many unknowns. Researchers don’t know how long the benefits might last. The general belief is that most patients who improve with TMS will continue to need some ongoing therapy for depression, whether it’s medication, counseling, additional TMS sessions or some combination of these therapies.

So far, TMS appears safe, although long-term effects — if any — aren’t well-defined. Short-term side effects usually are mild. They can include discomfort at the treatment site during the treatment session, tingling or twitching of the facial muscles during treatment, and headaches during or after treatment. Rarely, seizures can occur during therapy.

Source: Mayo Clinic

Routinely used to treat patients for heart attack or high blood pressure, beta blockers are known for their role in helping to protect the heart. A new study in the January issue of the journal Anesthesiology looks at the effects of beta blockers on surgical outcomes, revealing that the cardioprotective effects of the medication could be compromised by acute surgical anemia.

Blood loss and anemia are very common in patients during and after surgery; more than 30 percent of patients undergoing moderate- to high-risk surgery experience a significant drop in blood levels. The normal response of a patient’s body during significant blood loss is to increase cardiac output through increased heart rate to ensure sufficient delivery of oxygen to organs.

Beta blockers are used to treat a variety of conditions, including high blood pressure, heart attack, glaucoma and migraines. The medication works to reduce the heart rate, reducing blood pressure as a result. Beta blockers are often prescribed for patients around the time of surgery to provide protection of the cardiovascular system.

“Beta blockers are known to reduce death from cardiac complications after noncardiac surgery and have been recommended for patients with clinical risk factors. However, previous studies such as the POISE (Perioperative Ishemic Evaluation) trial published in the May 31, 2008 Lancet have revealed that increased stroke rates and mortality were associated with blood loss in patients treated with high doses of beta blockers,” said W. Scott Beattie, M.D., Ph.D., F.R.C.P.C., Fraser Elliot Chair in Cardiac Anesthesia, University Health Network, Toronto General Hospital in Toronto, Ontario, Canada.

Dr. Beattie further explained, “The natural response of the body to blood loss and the action beta blockers induce on the body create a paradox for treatment. Blocking the appropriate response of the body to anemia, as would happen with patients who are on or in need of beta blockers, may actually increase the risk of anemia-induced adverse cardiovascular events. “

About the Study

To determine if there is a significant interaction between the hemoglobin level and beta blocker effect, Dr. Beattie and colleagues performed a retrospective review of 4,378 noncardiac surgery patients at Toronto General Hospital from March 2005 to June 2006. Researchers compared the effect of acute anemia on adverse cardiovascular outcomes in two propensity score-matched cohorts; one containing patients treated with beta blockers and the other containing patients matched for cardiac, respiratory and hematologic risk factors that were not treated with beta blockers.

The review revealed that major cardiac complications and death rates were increased for patients treated with beta blockers who experienced more than a 35 percent drop in blood count (or hemoglobin). Researchers discovered that treatment with beta blockers was not harmful to patients if blood loss remained in a range of 30 to 35 percent.

Dr. Beattie concluded, “This study should alert us to the fact that, potentially, there may be ways to mitigate and prepare for the demonstrated risks of beta blockade. To validate these findings and to take the next steps in patient treatment and surgical safety, prospective studies are required to further investigate the importance of the interaction between hemoglobin blood levels and beta blocker effects.”

New for 2010 in Anesthesiology

As part of a mission to promote new discoveries and influence clinical practice, the January issue of Anesthesiology marks the debut of a newly designated “Education” section. This section is designed to highlight clinical material, making it more accessible and relevant for implementation in everyday clinical practice.

The American Society of Anesthesiologists

Anesthesiologists: Physicians providing the lifeline to modern medicine. Founded in 1905, the American Society of Anesthesiologists is an educational, research and scientific association with 43,000 members organized to raise and maintain the standards of the medical practice of anesthesiology and improve the care of the patient.

Source: American Society of Anesthesiologists (ASA)

Alimera Sciences, Inc., a privately held biopharmaceutical company that specializes in the research, development and commercialization of prescription ophthalmic pharmaceuticals, reported top-line results from the month 24 readout of the FAME Study.

The FAME Study consists of two Phase 3 pivotal clinical trials (Trial A and Trial B) for the use of Iluvien in the treatment of diabetic macular edema (DME). The primary efficacy endpoint for the FAME Study is the difference in the percentage of patients whose best corrected visual acuity (BCVA) improved by 15 or more letters from baseline on the ETDRS eye chart at month 24 between the treatment and control groups.

The month 24 analysis using the Full Analysis Set in Trial A demonstrated statistical significance with 26.8% (p value 0.029) of the low dose patients having an improvement in BCVA of 15 letters or greater over baseline and 26.0% (p value of 0.034) of the high dose patients having an improvement in BCVA of 15 letters or greater from baseline. In Trial B, the month 24 data demonstrated statistical significance with 30.6% (p value of 0.030) of the low dose patients having an improvement in BCVA of 15 letters or greater over baseline and 31.2% (p value of 0.027) of the high dose patients having an improvement in BCVA of 15 letters or greater from baseline.

The Full Analysis Set includes all 956 patients randomized into the FAME Study, with data imputation employed using last observation carried forward (LOCF) for data missing because of patients who discontinued the trial or are unavailable for follow up. (This data set is commonly referred to as the “intent to treat” population.)

In addition, both the low and high dose Iluvien showed greater numerical efficacy at month 24 than at month 18, a requirement for submission with 24 month data in the United States.

Safety was assessed for all patients treated in the study. Intraocular pressure (IOP) increases of 30 millimeters of mercury (mmHg) or greater at any time point, a key adverse event studied in the trial, were seen in 16.3% of the low dose patients and 21.6% of the high dose patients. Over the 24 month period, 2.1% of patients receiving the low dose and 5.1% of the patients receiving the high dose had undergone a trabeculectomy (filtration procedure) to reduce their eye pressure.

Based on these and other data, Alimera plans to seek approval of the low dose of Iluvien for the treatment of DME in the second quarter of 2010, followed by registration filings in various European countries and Canada. Submission of the NDA will be based on the month 24 safety and efficacy data while the FAME Study will continue to month 36.

“I am very proud of the Alimera team for having completed trials which we believe demonstrate efficacy at the month 24 clinical readout and am confident that we will submit an NDA application for Iluvien in 2010 for the treatment of DME. If approved, we believe this would be the first drug approved for the treatment of this condition,” said Dan Myers, president and CEO of Alimera Sciences. “Additionally, we appreciate the efforts of our clinical sites around the world that have managed and continue to manage the patients in the FAME Study.”

In addition to the analysis described above, as prospectively planned in the protocol, Alimera also conducted several other analyses of the 24 month data. These included a) an All Randomized and Treated (ART) analysis of the 24 month data that includes data from all subjects randomized and treated with values imputed for all missing data using the LOCF method, and b) a Modified ART analysis that utilizes the ART population, but excludes data collected subsequent to the use of treatments prohibited by protocol (such as intravitreal injections of Lucentis or triamcinolone acetonide) with the last observation prior to protocol violation imputed to month 24 using the LOCF method.

The results of these separate analyses were as follows: by the ART analysis, in Trial A, 26.8% of low dose patients and 26.2% of high dose patients gained 15 or more letters at 24 months compared with 14.7% of control patients (p = 0.029 and 0.032, respectively). In Trial B of the ART analysis, 31.3% of high dose and 30.8% of low dose patients gained 15 or more letters compared with 17.8% of control patients (p = 0.028 and 0.026 respectively). The results for both doses in both trials were statistically significant. By the Modified ART method, in Trial A 22.6% of patients in the low dose and 24.1% of patients in the high dose gained 15 or more letters compared with 12.6% of control patients (p = 0.057 and 0.026, respectively). Trial A was not statistically significant for either dose. In Trial B by Modified ART, 29.7% of patients in the low dose and 29.3% of patients in the high dose gained 15 or more letters compared with 13.3% of control patients (p = 0.004 and 0.005, respectively). The results for both doses were statistically significant.

The FAME study protocol provides that the primary assessment of efficacy will be based on the Modified ART dataset and that the other datasets will be considered secondary; the protocol did not specify the Full Analysis Set as a dataset for analyzing the study. However, consistent with the FDA-adopted International Conference on Harmonization guidance, it is anticipated that the FDA will consider the Full Analysis Set to be the most relevant population for determining safety and efficacy in Trials A and B.

A more detailed analysis will be presented in February 2010 at the Angiogenesis, Exudation and Degeneration 2010 Meeting in Miami, Florida.

ALIMERA SCIENCES RECEIVES NOTICES OF EXERCISE FOR AN ADDITIONAL $10 MILLION IN EXTENDED SERIES C FINANCING

On August 24, 2009, Alimera announced that it had closed an extension of its Series C financing in which it issued shares of its Series C preferred stock and warrants to purchase shares of its Series C preferred stock. By their terms, the warrants were to be exercised in full within 30 days of the delivery of top line data from the Company’s Phase III trials for Iluvien. Today, Alimera announced that it had received written notice from its principal warrant holders of their election to exercise the warrants. This warrant exercise, which will result in $10 million in proceeds to Alimera, will close in January 2010.

About the FAME Study

The Phase 3 FAME Study consists of two multi-center, randomized, double-masked trials for Iluvien in sites across the United States, Canada, Europe and India. The two trials have identical protocols and enrolled 953 patients across 101 academic and private practice centers. Patients in each trial were randomly assigned to one of three groups in a 2:2:1 randomization, respectively. One group received a high dose of Iluvien (an approximate initial 0.45 micrograms per day dose), a second received a low dose of Iluvien (an approximate initial 0.23 micrograms per day dose) and the third group (control) received sham. The sham included all the steps involved in the insertion procedure with the exception that patients in this group had a blunt inserter without a needle to apply pressure to the anesthetized eye in order to simulate an insertion. This procedure mimics an intravitreal insertion and helps to maintain proper patient masking.

About DME

DME, the primary cause of vision loss associated with diabetic retinopathy, is a disease affecting the macula, the part of the retina responsible for central vision. When the blood vessel leakage of diabetic retinopathy causes swelling in the macula, the condition is called DME. The onset of DME is painless and may go undetected by the patient until it manifests with the blurring of central vision or acute vision loss. The severity of this blurring may range from mild to profound loss of vision. The Wisconsin Epidemiologic Study of Diabetic Retinopathy found that over a 10-year period approximately 19% of diabetics studied were diagnosed with DME. Based on this study and the current U.S. diabetic population, Alimera estimates that there will be an incidence of approximately 340,000 cases of DME annually in the United States. As the population of people with diabetes increases, Alimera expects the annual incidence of diagnosed DME to increase as well.

About Iluvien®

Iluvien is an investigative, extended release intravitreal insert that Alimera is developing for the treatment of DME. Each Iluvien insert is designed to provide a therapeutic effect of up to 36 months by delivering sustained sub-microgram levels of fluocinolone acetonide (FA). Iluvien is inserted in the back of the patient’s eye to a position that takes advantage of the eye’s natural fluid dynamics. Iluvien is inserted with a device that employs a 25-gauge needle, which allows for a self-sealing wound.

About Alimera Sciences, Inc.

Alimera Sciences is a biopharmaceutical company that specializes in the research, development and commercialization of prescription ophthalmic pharmaceuticals. Presently the company is focused on diseases affecting the back of the eye, or retina. Its most advanced product candidate is Iluvien®, which is being developed for the treatment of diabetic macular edema, or DME.

Alimera is also pursuing the development, license and acquisition of rights to compounds and technologies with the potential to treat diseases of the eye that Alimera believes are not well treated by current therapies. Alimera has entered into agreements with Emory University, where by it acquired exclusive, worldwide rights under patent applications covering two classes of nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase inhibitors. Alimera’s initial focus is on the use of NADPH oxidase inhibitors in the treatment of the dry form of age-related macular degeneration (AMD), particularly the late stage of this condition known as geographic atrophy. Alimera plans to evaluate the use of NADPH oxidase inhibitors in the treatment of other diseases of the eye, including the wet form of AMD and diabetic retinopathy.

Source: Alimera Sciences, Inc

View drug information on Lucentis.

The Norwegian pharmaceutical company Lytix Biopharma AS announced approvals from the Norwegian Medicines Agency (”Statens legemiddelverk”) and the Swedish Medical Products Agency (”Läkemedelverket”) to commence Phase I clinical trials of OncoporeTM (LTX-315) for the treatment of cancer.

According to Lytix Biopharma CEO Gunnar Sælid, “We are delighted to announce the regulatory approval by the Norwegian and Swedish Authorities to test our very interesting experimental drug OncoporeTM (LTX-315) in the clinic. I am extremely pleased with the efforts put in by our Drug Development teams this year, with all projects progressing well according to our plans. For the Company this is an important study, validating the attractiveness of our platform in oncology. We will now have two programs in clinical trials; on the one hand our topical antimicrobial drug, and now our novel treatment for cancer”.

In preclinical models LTX-315 has demonstrated the ability to effect necrotic killing of cancer cells. Simulatenously it also causes the release of danger signals from the stressed and dying cells that trigger a beneficial activation of the immune system.

“The study will start in the beginning of 2010 and will be run at two centers, The Norwegian Radium Hospital - National Hospital in Oslo, as well as the Karolinska University Hospital in Stockholm, Sweden. Initially, the Phase I study will establish a safe and tolerated dose of LTX-315 when given to solid tumours amenable to injection. OncoporeTM (LTX-315) has the potential to becoming a valuable new agent for the treatment of cancer”, says Jon Amund Eriksen, Director of Product Development, Oncology at Lytix Biopharma AS. The clinical trial is supported by grants from The Norwegian Cancer Association (”Kreftforeningen”), The Norwegian Research Council (”Forskningsrådet”) and Innovation Norway (”Innovasjon Norge”).

About OncoporeTM (LTX-315)

LTX-315 is an investigational treatment for cancer based on the biological principle of innate immune effectors, lytic peptides. The drug recognises charges in cell membranes and, in a dose dependent manner, induces immunogenic cell stressing and rapid cell lysis. When injected intra-tumorally LTX-315 causes dramatic and rapid cell lysis and tumour necrosis. The drug has been tested in in vitro and in vivo models, and has undergone formal preclinical safety and toxicology studies. The Phase I/II study is expected to commence in the beginning of 2010.

Source
Lytix Biopharma AS

The NPA (National Pharmacy Association) has expressed concern over the level of detail which PCTs need to submit for their Quality Accounts and how this could impact on community pharmacy.

Margaret Peycke NPA External Relations Manager said: “Whilst we fully support the delivery of quality services and improvement in service delivery and acknowledge that organisations need to reflect on their practice in order to improve, we believe that data gathering generally and the production of Quality Accounts specifically should not overwhelm the delivery of services and lead to reduced patient care.”

“Many community pharmacies are small provider organisations and do not necessarily have the administrative capacity to produce detailed documents - the data they need to submit must be commensurate to their activity. Community pharmacies already suffer from many cumbersome administrative requirements and to add to this may in fact deter them from providing additional services for the benefit of their communities, rather than improve the delivery of the services they provide.”

Regional and national pharmacy chains will face other but equally considerable administrative challenges. The cost of providing Quality Accounts must be calculated accurately and that amount factored into practice payments when the Department of Health is negotiating with the Pharmaceutical Services Negotiating Committee (PSNC).

Source
National Pharmacy Association

BioMedReports.Com, the news portal which covers Wall Street’s biomedical sector and delivers financial and investment intelligence to a community of highly informed investors, has published an exclusive interview with the CEO of Novelos Therapeutics, Inc. (OTCBB: NVLT), Harry S. Palmin.

It’s become pretty obvious, even to the most casual biotech sector observer, that patients involved in Novelos’ pivotal Phase III trial for lung cancer are living longer than expected.

“These patients with a median survival of eight to ten months unfortunately die pretty quickly,” explains Palmin. “One year survival, which is another way to look at this, is just about 40%.”

But Wall Street has begun to take more interest in the company and the study since over a year and a half after the enrollment target of patients was reached, the number of the expected deaths has not yet occurred.

In the interview, Palmin reveals:

“…Avastin is the only drug in non-small cell lung cancer, first line treatment, that showed a survival advantage. They showed a two month survival advantage, 12.3 months versus 10.3, but the drug has severe toxicities associated with it on top of the chemotherapy toxicities and it’s very expensive. It’s also only available to very few lung cancer patients because the histology it works for is non-squamous.

“The point that I’m trying to make is that given our current statistical projections, we should be on track to achieve or possibly even exceed our possible twelve and a half month median survival target.

“By way of background, we started the pivotal Phase III on lung cancer on the back of three Phase IIs,” explains Palmin. “We saw dramatic survival advantages, better anti-tumor effects and in the United States, we saw doubling response rates and better toleration of chemotherapy.”

The complete interview is available now at BioMedReports.Com.

Biotech investors interested in accessing the news portal’s complete database of clinical trials and upcoming FDA decisions can access that informatio here.

Source
BioMedReports.Com

Actelion Ltd (SIX: ATLN) announced today that the first phase III study with almorexant (RESTORA 1) has met its primary endpoint, superiority of the dual orexin receptor antagonist almorexant compared to placebo on objective and subjective wake after sleep onset (WASO). The finding was highly significant (p<0.001). In addition, several secondary endpoints of the study were met with statistical significance.

In RESTORA 1, the use of almorexant was well-tolerated. However, in this study as well as in the ongoing non-pivotal program, certain safety observations were made that will require further evaluation and assessment in longer-term Phase III studies. The Phase III studies are currently in preparation - in both adults and elderly patients suffering from primary insomnia - and will evaluate long-term efficacy and safety.

Professor Jed Black, M.D. and VP Sleep Development at Actelion, commented: “In this two-week study, almorexant has demonstrated clinically meaningful effects on both sleep induction and sleep maintenance for patients suffering from primary insomnia. I am especially encouraged that these effects were maintained both throughout the night and throughout the 16-day treatment period.”

Jean-Paul Clozel, M.D and Chief Executive Officer of Actelion, commented: “As a result of the use of an active reference arm of zolpidem 10mg in RESTORA 1, we have now obtained a first promising insight of the impact of our dual orexin receptor antagonist almorexant compared to the impact of a traditional GABA-agonist.”

Jean-Paul Clozel concluded: “Additional studies are being planned to further establish the clinical profile of almorexant. We will explore aspects of sleep quality, absence of addiction and improved next-day performance. Chronic use studies in both adults and elderly will further evaluate the safety profile of this innovative agent.”

About the RESTORA program

Actelion has initiated a comprehensive Phase III program named RESTORA (REstore physiological Sleep with The Orexin Receptor antagonist Almorexant) to evaluate safety and efficacy of 100 and 200 mg doses in adults and elderly patients diagnosed with primary insomnia. The RESTORA program will also include dedicated profiling studies. The non-pivotal program is ongoing. The longer-term Phase III studies are in preparation.

About RESTORA 1

RESTORA 1 was a multi-center, double-blind, randomized, placebo-controlled, active reference (zolpidem), parallel-group polysomnography study to evaluate efficacy and safety of 16-day oral administration of almorexant 200mg and 100mg in adult 709 patients with chronic primary insomnia. Enrolment took place in 90 clinical study centers in Australia, Europe and Israel.

Detailed study results will be made available at upcoming scientific meetings or through publication in peer-reviewed scientific journals.

Source
Actelion Ltd

PHT Corporation announced that Sanofi Pasteur is using PHT’s LogPad® System and StudyWorksTM online portal for a Phase II trial to develop a vaccine against the Clostridium difficile bacterium. PHT is the leading provider of ePRO solutions used in pharmaceutical and biotechnology clinical trials worldwide. Sanofi Pasteur, a world leader in the vaccines industry, is the vaccines division of the sanofi-aventis Group.

Sanofi Pasteur is working with PHT Corporation to collect direct capture patient experience data quickly, safely and accurately at medical centers across the United Kingdom and the United States. Sanofi Pasteur’s phase IIb trial plans to study over 600 people with an acute infection caused by C. difficile. The bacterium spreads through the human intestinal system causing diarrhea, fever, nausea, abdominal pain, and serious intestinal conditions such as colitis, which can result in death.

Vicki Tyler, a Clinical Trial Manager at Sanofi Pasteur’s Massachusetts facility, explained that, unlike with a paper diary, sites and sponsors know they are receiving real-time trial data when using the LogPad. Sanofi Pasteur has used PHT’s ePRO solutions successfully for other trials and expects to achieve specific improvements in the data gathering processes, data quality, patient compliance, and trial process efficiency by using the LogPad instead of paper for this trial.

PHT Vice President of Marketing and Product Management Sheila Rocchio said, “With paper diaries, researchers can only hope that patients remember to complete their diaries. When patients comply, the data are incomplete and often inaccurate. PHT’s LogPad time-stamps all data entries, providing an immediate data advantage over paper. Using ePRO promotes safety and accuracy in studies, enabling sponsors to bring new drugs to market faster and more economically.”

Source
PHT Corporation

Several structurally similar small molecules appear capable of protecting cells from alpha-synuclein toxicity in multiple models of Parkinson’s disease, according to Whitehead Institute researchers. Misfolded copies of the alpha-synuclein protein in brain cells are a hallmark of Parkinson’s disease.

“In this research, we used yeast as a Parkinson’s disease model system to identify the compounds that really work in two higher order model systems of Parkinson’s,” says Julie Su, a first co-author on the paper describing the research and a former postdoctoral researcher in Whitehead Member Susan Lindquist’s lab. “And that shows that those compounds’ targets are highly conserved over a billion years of evolution.”

Parkinson’s disease is a neurodegenerative disorder characterized by tremors, muscle rigidity, and slowed movements. In the neurons of Parkinson’s patients’ brains, researchers have noted Lewy bodies, abnormal spheres composed of the protein alpha-synuclein. There is currently no cure for the disease, and current Parkinson’s therapies only address disease symptoms, not the disease’s cellular cause.

In their article in Disease Models and Mechanisms (DMM), Lindquist scientists report that four related small molecules prevented the development of several cellular traits associated with Parkinson’s disease, including the accumulation of alpha-synuclein deposits in the cell, improper protein trafficking from one organelle to another, and damage inflicted on the cells’ engines, the mitochondria.

The research is based on a type of brewer’s yeast modified to produce too much of the alpha-synuclein protein in its cells. The resulting cells manifest adverse effects similar to those experienced in brain cells from Parkinson’s patients.

Using this yeast strain, the Lindquist team screened 115,000 small compounds to see which ones alleviate the Parkinson’s-like traits. During a screen, a compound is added to a small amount of yeast. Researchers can then easily and efficiently detect if that compound changes the yeast’s growth rate, compared to a control. The technique takes advantage of the yeast’s normally fast growth, which allows researchers to quickly test thousands of compounds, a process that is not possible in other frequently-used Parkinson’s disease models.

Four compounds were found to restore the alpha-synuclein yeast cells’ growth to 50% of normal yeast cells. Yeast cells that were not treated with the compounds died. The four compounds have similar chemical structures, a finding that indicates they may be acting on the same target or targets. The researchers also identified two commercially available compounds with similar chemical structures and used those in further tests.

To determine if the six compounds would work in animal models of Parkinson’s, the scientists tested the compounds in the round worm Caenorhabditis elegans and in rat neurons. In both of these disease models, cells overproduce alpha-synuclein resulting in the same deleterious effects as in the yeast model. During testing, the first four compounds were able to rescue the round worms, while in the rat neurons, three of the four original compounds and one of the commercial compounds improved the nerve cells’ growth.

In all of the models, the compounds improved protein trafficking and decreased mitochondrial damage.

“Those two things are obviously related,” says Pavan Auluck, first co-author and a visiting scientist in the Lindquist lab. “We’re trying to figure out what the connections are between them. And there are a number of ways they can be related.”

Lindquist agrees: “There are very deeply rooted processes that connect protein trafficking and mitochondrial viability,” says Lindquist, who is also a Howard Hughes Medical Institute investigator and a professor of biology at MIT. “That emphasizes that the underlying problem caused by alpha-synuclein is a general cellular defect that is part of the machinery of all eukaryotic cells. The specific problems in Parkinson’s are due to the neurons being particularly sensitive to that process going awry.”

As for the future of the specific compounds identified in this study, Daniel Tardiff, a Lindquist postdoctoral researcher, remains optimistic.

“Theoretically if a compound is having a beneficial effect on yeast cells, and in a worm, and in primary neurons, then possibly through years and years of work, it might actually be a potential therapeutic avenue or drug,” says Tardiff. “Though we started in yeast, one of those compounds could actually have some potential for human health in Parkinson’s disease. That’s always a lofty goal.”

The MGH/MIT Morris Udall Center of Excellence in Parkinson Disease Research, the Michael J. Fox Foundation, and the Howard Hughes Medical Institute (HHMI) provided funding for this research.

Susan Lindquist’s primary affiliation is with Whitehead Institute for Biomedical Research, where her laboratory is located and all her research is conducted. She is also a Howard Hughes Medical Institute investigator and a professor of biology at Massachusetts Institute of Technology.

Full Citation:

“Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and mitochondrial dysfunction in Parkinson disease models”

Disease Models and Mechanisms, published online December 28, 2009

Linhui Julie Su (1,9,), Pavan K. Auluck (1,3,), Tiago Fleming Outeiro (1,10,), Esti Yeger-Lotem (1,4,11), Joshua A. Kritzer (1,12), Daniel F. Tardiff (1), Katherine E. Strathearn (5), Fang Liu (5), Songsong Cao (6), Shusei Hamamichi (6), Kathryn J. Hill (7), Kim A. Caldwell (6), George W. Bell (1 ), Ernest Fraenkel (4), Antony A. Cooper (7), Guy A. Caldwell (6), J. Michael McCaffery (8), Jean-Christophe Rochet (5), and Susan Lindquist (1,2).

References

1. Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA

2. Howard Hughes Medical Institute, Cambridge, MA, 02142 USA

3. Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114 and Harvard Medical School, Boston MA, 02115 USA

4. Department of Biological Engineering, MIT, Cambridge, MA, 02142 USA

5. Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907 USA

6. Department of Biological Sciences, University of Alabama, Tuscaloosa, AL, 35487 USA

7. Diabetes Program, Garvan Institute of Medical Research, Sydney, NSW 2010 Australia

8. Integrated Imaging Center, Department of Biology, Johns Hopkins University, Baltimore, MD, 21218 USA

9. Present Address: Adnexus Therapeutics, A Bristol-Myers Squibb R&D Company, Waltham, MA, 02453, USA

10. Present Address: Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular and Instituto de Fisiologia, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal

11. Present Address: Department of Clinical Biochemistry, Soroka Medical Center and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel.

12. Present Address: Department of Chemistry, Tufts University, Medford, MA 02155, USA

Source: Whitehead Institute for Biomedical Research

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