ImmuPharma PLC announced the final results from a Phase IIb trial of LUPUZOR™ in active patients with Systemic Lupus Erythematosus (SLE). Lupuzor™ administered at 200 mcg once-a-month for 3 months plus standard of care achieved a clinically significant improvement in patient response rate as measured by the combined score compared to placebo plus standard of care. The study results also show that Lupuzor™ was generally well tolerated, with adverse event rates lower with Lupuzor™ when compared to placebo.

Highlights

- Lupuzor™ achieved a clinically significant improvement in patient response rate versus placebo in the intention to treat (ITT) analysis

- The improvement was statistically significant in a subgroup (90% of the ITT population) of moderate to severe patients
- 62% of this sub-group of patients were responders according to both a composite clinical score and a decrease of 4 points of the SLEDAI score when treated with Lupuzor™ 200 µg every 4 weeks for 12 weeks compared to 41% on placebo

- Lupuzor™ was generally well tolerated with fewer serious AEs leading to discontinuation

Details of the Phase IIb study with Lupuzor™

This phase IIb study was a randomized, double-blind placebo controlled, dose-ranging study in 150 (initially planned 204) patients designed to evaluate the efficacy of Lupuzor™ in a three-month treatment period of either subcutaneous (SC) injection of 200 mcg once-a-month (4qw) or 200 mcg twice-a-month (2qw) or placebo in addition to standard of care and followed by a 3 month follow-up period.

The primary efficacy endpoint of the study was based on the combined score, which is defined by: (1) a reduction from baseline of at least 4 points on the 2K-SLEDAI disease activity scale (which indicates a clinically important reduction in SLE disease activity); (2) no worsening of disease as measured by the Physician’s Global Assessment (worsening defined as an increase of 0.30 points or more from baseline); and (3) no new BILAG A organ domain score (which indicates a severe flare of lupus disease activity) and no more than one new BILAG B organ domain score (which indicates a moderate flare of disease activity). An additional end-point was the response rate based only on the decrease of the SLEDAI score by 4 points.

An interim analysis was performed and included 125 patients out of the ITT population having completed by mid November 2008 the week 12 assessments, approximately half of them having also completed the 12 week follow-up period. These results were announced in January 2009 indicating that Lupuzor™ administered at a 200 mcg dose once-a month for 3 months was statistically significantly superior to placebo, using a decrease of 4 points of the SLEDAI score to define a responder with drop-outs being considered according to the protocol as non-responders. As the study showed a statistically significant improvement even with a much lower number of patients, ImmuPharma decided to stop the recruitment of further patients. All patients already recruited completed the study according to protocol.

The study was planned to originally enroll any patient with SLEDAI ? 6. Soon after study commencement the protocol was formally amended to ensure only patients with a clinical SLEDAI ? 6 (defined as the moderate to severe subgroup) were included.

The study was terminated with an ITT population of 147 patients (Intent To Treat population) and the moderate to severe subgroup of 134 patients (90% of the ITT population) in line with the amended protocol.

Key findings from the Phase IIb study with Lupuzor™

The analysis of the study revealed for Week 12:

1) ITT population:

a) Primary endpoint (Combined score responders): Lupuzor™ once-a-month 53% (p = 0.048). Lupuzor™ twice-a-month: 45%; placebo 36%

b) SLEDAI score responders: Lupuzor™ once-a-month 53% (p = 0.073). Lupuzor™ twice-a-month: 45%; placebo 38%

2) Moderate to severe subgroup Population Week 12
a) Primary endpoints (Combined score responders): Lupuzor™ once-a-month 62% (p = 0.016). Lupuzor™ twice-a-month: 48%; placebo 39%

b) SLEDAI score responders: Lupuzor™ once-a-month 62% (p = 0.026). Lupuzor™ twice-a-month: 48%; placebo 41%

All treatments (Lupuzor™ or placebo) were administered in addition of standard of care which may include patients on low dose steroids (< 80mg prednisone/week). 200 µg of Lupuzor™ administered once-a-month during 3 months (total 600 µg) achieved a clinically and statistically meaningful improvement of the moderate to severe subgroup. An analysis after a further 12 week follow-up (with only standard of care) revealed that the responder rates further increased to reach about 70% in the moderate to severe subgroup compared to 59% on placebo. Lupuzor™ was well tolerated and its safety profile was better than placebo with less drop-outs (1 vs 8) and less serious AEs leading to discontinuation.

Lupus is a disease that involves an inappropriate functioning of the immune system in that the immune-competent T and B cells are generating antibodies against certain self proteins. Lupuzor™ corresponds to the sequence 131-151 of the 70k snRNP protein with a Serine phosphorylated in position 140. It was discovered by France’s National Center for Scientific Research (Centre National de la Recherche Scientifique) and further developed by ImmuPharma and is now licensed to Cephalon Inc. Lupuzor™ modulates both the auto-reactive T and B cells involved in Lupus in order to render the functioning of the immune system more appropriate while maintaining its overall efficacy.

Commenting on the detailed results of the study, Dr Robert Zimmer, MD. PhD, ImmuPharma’s President and Chief Scientific Officer said: “We are absolutely delighted that Lupuzor™’s phase IIb study has delivered such very encouraging clinical efficacy data reaching statistical significance in the moderate to severe subgroup (90% of the ITT population) and with an overall efficacy peaking at 70%. The information gathered in this study, in addition to the very small number patients needed to prove efficacy, paves the way for a medical and commercial success of Lupuzor™.

Frank Baldino Jr, Ph.D, Cephalon’s Chairman & CEO added: “We are pleased to have the opportunity to further develop Lupuzor and potentially bring a new medication to the lupus patients who have waited 50 years for new therapy.”

Source
ImmuPharma PLC

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.

Acupuncture can help people with chronic low back pain feel less bothered by their symptoms and function better in their daily activities, according to the largest randomized trial of its kind, published in the May 11, 2009 Archives of Internal Medicine. But the SPINE (Stimulating Points to Investigate Needling Efficacy) trial raises questions about how the ancient practice actually works.

Compared to the group that got usual care, results were similar for all three of the SPINE trial’s acupuncture groups: individualized, standardized, and simulated (without going through skin). Of the people who got any kind of acupuncture, an extra one in five were functioning significantly better at the end of the seven-week treatment - and an extra one in eight were still functioning better at one year.

“This study suggests that acupuncture is about as effective as other treatments for chronic back pain that have been found helpful,” said SPINE trial leader Daniel C. Cherkin, PhD, a senior investigator at Group Health Center for Health Studies in Seattle. “But we found that simulated acupuncture, without penetrating the skin, produced as much benefit as needle acupuncture - and that raises questions about how acupuncture works.”

The SPINE trial included 638 adult patients at two nonprofit health plans: Group Health Cooperative in Seattle and Northern California Kaiser Permanente in Oakland. They all rated the “bothersomeness” of their chronic low back pain as at least a 3 on a 0-to-10 scale. None of them had received acupuncture before. They were randomly assigned to one of four groups:

• Individualized needle acupuncture, involving a customized prescription for acupuncture points from a diagnostician

• Standardized needle acupuncture, using a single prescription for acupuncture points on the back and backs of the legs, which experts consider generally effective for chronic low back pain
• Simulated acupuncture on those same standardized points, mimicking needle acupuncture but instead of a needle using a toothpick in a needle guide tube without penetrating the skin
• Usual care, which is the standard medical care they would have gotten anyway - and that all patients in all groups received

Everyone in the three acupuncture groups (individualized, standardized, or simulated) was treated twice a week for three weeks, and then weekly for four weeks. At eight weeks, half a year, and one year, researchers measured back-related dysfunction and how much symptoms bothered patients.

The SPINE team found that at eight weeks all three acupuncture groups were functioning substantially better, while the group getting only usual care was functioning only slightly better. Dysfunction scores improved significantly more for all three acupuncture groups than for the usual care group. These benefits lasted for a year, although they waned over time.

Notably, the outcomes for groups that received the needle and simulated forms of acupuncture did not differ significantly. So, although acupuncture effectively treated low back pain, that therapeutic benefit seemed to require neither tailoring acupuncture needle sites to an individual patient nor inserting needles into the skin.

“We don’t know precisely why people got back pain relief from the simulated acupuncture,” said Cherkin’s co-author Karen J. Sherman, PhD, MPH, a senior investigator at Group Health Center for Health Studies. “Historically, some types of acupuncture have used non-penetrating needles. Such treatments may involve physiological effects that make a clinical difference.” Or it might be all about the mind-body connection, she said: “Maybe the context in which people get treatment has effects that are more important than the mechanically induced effects.”

Western medicine does not have highly effective medical treatments for chronic back pain, Cherkin said. Back pain is the number-one reason that Americans use complementary and alternative medicine (CAM), including acupuncture.

The National Center for Complementary and Alternative Medicine (NCCAM), part of the National Institutes of Health, funded the SPINE trial.

“The findings of this research show that acupuncture-like treatments, including simulated acupuncture, can elicit positive responses,” said Josephine P. Briggs, MD, director of NCCAM. “This adds to the growing body of evidence that something meaningful is taking place during acupuncture treatments outside of actual needling. Future research is needed to delve deeper into what is evoking these responses.”

Cherkin and Sherman’s SPINE trial co-authors were Richard A. Deyo, MD, MPH, of Oregon Health & Science University in Portland; Partap S. Khalsa, DC, PhD, of NCCAM’s Division of Extramural Research; Andrew L. Avins, MD, MPH, Luisa Hamilton, MD, and Alice Pressman, MS, of Northern California Kaiser Permanente in Oakland; William E. Barlow, PhD of Cancer Research and Biostatistics and Group Health Center for Health Studies; and Laura Ichikawa, MS, Janet H. Erro, RN, MN, Kristin Delaney, MPH, and Rene Hawkes of Group Health Center for Health Studies.

Source:
Rebecca Hughes

Group Health Cooperative Center for Health Studies