March 22, 2011 12:50 PM Eastern Daylight Time 

Phase III data presented at AAAAI builds upon Sunovion legacy in respiratory therapies

MARLBOROUGH, Mass.–(BUSINESS WIRE)–Sunovion Pharmaceuticals inc. (Sunovion) today announced that data from a large scale, 671-patient, Phase III clinical study of ciclesonide nasal aerosol in a hydrofluoroalkane (HFA) formulation were presented in three separate scientific posters at the 2011 annual meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) in San Francisco, California. the data show statistically significant improvements in reflective total ocular symptom score (rTOSS) in patients treated once daily with 74 µg of ciclesonide nasal aerosol as well as statistically significant improvements in nasal symptoms of seasonal allergic rhinitis (SAR) in patients treated once daily with both 74 µg and 148 µg of ciclesonide nasal aerosol. the overall incidence of adverse events (including epistaxis) was low and comparable to placebo. furthermore, the data also demonstrated statistically significant improvements with 74 µg of ciclesonide nasal aerosol in the overall rhinoconjunctivitis quality of life questionnaire (RQLQ) vs. placebo with a difference of 0.64.

“A Post-Hoc Analysis of Asthma Control and Lung Function following Treatment with Ciclesonide 80 ?g HFA-MDI twice Daily in Subjects with Mild-to-Moderate Persistent Asthma Previously Receiving low Dose Fluticasone Propionate/Salmeterol”

the delivery system in development is designed to dispense a small volume of the fine, dry mist of ciclesonide medication to a patient’s nose. This delivery system may be able to reduce some of the sensory effects such as back-of-the-throat run-off and run-out out of the nose that sometimes occur with aqueous-based corticosteroids for the treatment of allergic rhinitis.

“These findings indicate that ciclesonide HFA nasal aerosol may offer value for patients with seasonal allergic rhinitis including symptoms such as congestion, itchy / watery eyes and itchy nose,” said Charles P. Andrews, MD, of Diagnostics Research Group and a lead investigator of this ciclesonide HFA nasal aerosol clinical study. “We are encouraged by the results and look forward to continuing our efforts to develop treatment options for allergy sufferers.”

About the Phase III Ciclesonide HFA Nasal Aerosol (CIC-HFA) SAR Study

In this Phase III, placebo-controlled, double blind, parallel group study, 671 subjects, 12 years of age or older with SAR were randomized to either CIC-HFA 74 µg (N=226), 148 µg (N=225) or placebo (N=220), administered once-daily in the morning for two weeks during the Texas Mountain Cedar pollen season.

Efficacy was evaluated by subject-reported reflective and instantaneous total nasal symptom scores (rTNSS and iTNSS) assessing the individual nasal symptoms of nasal congestion, itching, sneezing, and runny nose. Efficacy was also evaluated by subject-reported reflective and instantaneous total ocular symptom scores (rTOSS and iTOSS) assessing the individual ocular symptoms of tearing, itchy and red eyes.

furthermore, this study measured the improvement in rhinoconjunctivitis related quality of life by administering a rhinoconjunctivitis quality of life questionnaire with standardized activities (RQLQ[S]).

Results from the Ciclesonide HFA Nasal Aerosol (CIC-HFA) SAR Study Poster Presentations:

• A Study Evaluating the Efficacy and Safety of Ciclesonide Hydrofluoroalkane Nasal Aerosol in the Relief of Nasal Symptoms of Seasonal Allergic RhinitisBoth CIC-HFA 74 µg and 148 µg demonstrated a statistically significant improvement in rTNSS (P<0.0001 for both), iTNSS (P<0.001 for both) and improvements in the individual nasal symptoms of congestion, nasal itching, sneezing and runny nose.the incidence of adverse events (including epistaxis) reported from this study for both doses of CIC-HFA were low and comparable to placebo.

• An Evaluation of the Effect of Ciclesonide Hydrofluoroalkane Nasal Aerosol on the Ocular Symptoms of Seasonal Allergic RhinitisCIC-HFA 74 µg demonstrated a statistically significant improvement in rTOSS (P=0.0124) and CIC-HFA 74 µg (P<0.05) and 148 µg (P<0.05) demonstrated improvement in iTOSS and individual ocular symptoms associated with SAR.

• Results of the Rhinoconjunctivitis Related Quality of Life Questionnaire Administered to Subjects with Seasonal Allergic Rhinitis following Treatment with Ciclesonide Hydrofluoroalkane Nasal AerosolBoth CIC-HFA 74 µg (P<0.0124) and 148 µg (P-value not determined) demonstrated improvements in the overall RQLQ[S].

In addition to the ciclesonide HFA nasal aerosol data presented at AAAAI, Sunovion also presented a poster titled, “A Post-Hoc Analysis of Asthma Control and Lung Function following Treatment with Ciclesonide 80 ?g HFA-MDI twice Daily in Subjects with Mild-to-Moderate Persistent Asthma Previously Receiving low Dose Fluticasone Propionate/Salmeterol” on data pertaining to the inhaled corticosteroid (ICS) asthma therapy, ALVESCO® (ciclesonide HFA inhalation aerosol). the data indicated that ALVESCO monotherapy maintained pulmonary function as measured by FEV1 in patients with mild-to-moderate persistent asthma, who were previously treated with combination low dose ICS and Long Acting Beta Agonist (LABA) therapy.1

About Allergic Rhinitis

Allergic rhinitis, which is commonly referred to as hay fever, is a collection of symptoms, predominantly in the nose and eyes, to allergens such as dust, dander and pollen. the sensitized immune system produces antibodies to these allergens, which cause chemicals called histamines to be released into the bloodstream, causing itching, swelling of affected tissues, mucus production, hives, rashes and other symptoms. Symptoms vary in severity from person to person.2

Allergic rhinitis is estimated to affect approximately 60 million people in the United States. Specifically, it is estimated that between 10% and 30% of adults and as many as 40% of children are affected by the disease. Approximately 12 million physician office visits each year are attributed to allergic rhinitis.3

SAR, which is also often referred to as hay fever, is caused by an allergy to the pollen of trees, grasses, weeds or mold spores. Depending on the allergen, the section of the country and the pollination periods, SAR may occur in the spring, summer or fall and may last until the first frost.

some people have symptoms of rhinitis no matter what the season. This is referred to as perennial allergic rhinitis, and it can be caused by allergens such as animal dander, indoor mold, dust mites and cockroaches.4

About Sunovion Pharmaceuticals inc. (Sunovion)

Sunovion is a leading pharmaceutical company dedicated to discovering, developing and commercializing therapeutic products that advance the science of medicine in the central nervous system (CNS) and respiratory disease areas and improve the lives of patients and their families. Sunovion’s drug development program, together with its corporate development and licensing efforts, has yielded a portfolio of pharmaceutical products including LATUDA® brand lurasidone HCl, LUNESTA® brand eszopiclone, XOPENEX® brand levalbuterol HCI Inhalation Solution, XOPENEX HFA® brand levalbuterol tartrate inhalation aerosol, BROVANA® brand arformoterol tartrate inhalation solution, OMNARIS® brand ciclesonide nasal spray and ALVESCO® brand ciclesonide HFA inhalation aerosol.

Sunovion, an indirect, wholly-owned subsidiary of Dainippon Sumitomo Pharma co., ltd., is headquartered in Marlborough, Mass. More information about Sunovion Pharmaceuticals inc. is available at sunovion.com.

About Dainippon Sumitomo Pharma co., ltd. (DSP)

DSP is a multi-billion dollar, top-ten listed pharmaceutical company in Japan with a diverse portfolio of pharmaceutical, animal health and food and specialty products. DSP aims to produce innovative pharmaceutical products in the CNS field, which has been designated as the key therapeutic area and will also focus in on other specialty disease categories with significant unmet medical needs, which are designated as frontier therapeutic areas. DSP is based on the merger in 2005 between Dainippon Pharmaceutical co., ltd., and Sumitomo Pharmaceuticals co., ltd. Today, DSP has more than 7,000 employees worldwide. Additional information about DSP is available through its corporate website at ds-pharma.com.

1 Meltzer EO, Korenblat PE, Weinstein SF, et al. Efficacy and safety evaluation of ciclesonide in mild-to moderate persistent asthma previously treated with inhaled corticosteroids. Allergy Asthma Proc 30:293-303, 2009.

2 Medline plus, a service of the U.S. National Library of Medicine and the National Institutes of Health. [Internet]. Available from nlm.nih.gov/medlineplus/ency/imagepages/19319.htm. Accessed: February 25, 2011.

3 American Academy of Allergy, Asthma and Immunology (AAAAI). [Internet]. Available from http:/aaaai.org/media/statistics/allergy-statistics.asp. Accessed: February 25, 2011.

4 American Academy of Allergy, Asthma and Immunology (AAAAI). [Internet]. Available from aaaai.org/patients/gallery/rhinitissinusitis.asp. Accessed: February 25, 2011.

LATUDA is a registered trademark of Dainippon Sumitomo Pharma co., ltd. LUNESTA, XOPENEX, XOPENEX HFA and BROVANA are registered trademarks of Sunovion Pharmaceuticals inc. OMNARIS and ALVESCO are registered trademarks of Nycomed GmbH.

For a copy of this release or any recent release,visit Sunovion’s web site at sunovion.com

Action Points  

• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Explain that immunotherapy for kids’ milk allergy may be far more effective with oral rather than sublingual dosing.
• Note that the children’s reactions to oral dosing required treatment more often with antihistamines or with inhaled beta-agonists, but there was no difference in the rate of reactions requiring epinephrine.
• Note that any form of immunotherapy for food allergies remains investigational and may not reach routine clinical practice for years yet.

SAN FRANCISCO — Immunotherapy for kids’ milk allergy may be far more effective with oral rather than sublingual dosing — although at the cost of more severe adverse events, researchers found in the first head-to-head comparison of therapy.

Oral immunotherapy allowed 60% (nine of 15) of the children with previously severe reactions to dairy to drink a full 8 oz cup of milk without problems during treatment, but only one of the ten on sublingual immunotherapy could pass the same desensitization challenge (P<0.01).

The study by Corinne Keet, MD, of John’s Hopkins Children’s Center in Baltimore, and colleagues was reported here at the American Academy of Allergy, Asthma & Immunology meeting.

Keets’s group also reported that oral doses of powdered milk given with food didn’t cause more symptoms overall than a liquid extract held under the tongue (25% versus 29% of doses caused symptoms).

But the children’s reactions to oral dosing required treatment more often with antihistamines (11% versus 1%) or with inhaled beta-agonists (1% versus 0.1%).

The most serious reactions requiring epinephrine, though, were equally uncommon at less than 0.1% for both groups.

It came as no surprise that oral immunotherapy carried more adverse effects, noted coauthor a. Wesley Burks, MD, of Duke University Medical Center, at a press conference where the study results were discussed.

The overall evidence suggests that about 15% of children cannot tolerate oral immunotherapy right from the start, largely due to gastrointestinal side effects, Burks pointed out.

But the lack of any options to treat food allergy aside from avoidance and symptom management makes the evidence on efficacy for oral immunotherapy “exciting and encouraging, though very preliminary,” added another study coauthor Robert Wood, MD, of Johns Hopkins, who also spoke at the press conference.

Hugh a. Sampson, MD, of the Mt. Sinai School of Medicine in New York City, who was not involved in the study, agreed that oral immunotherapy looks most promising to treat kids who can’t tolerate eating raw or baked forms of a food.

“It’s nice to finally tell patients that we may be able to do something other than take things away from them,” he said at the press conference. “That’s very exciting.”

All agreed, though, that any form of immunotherapy for food allergies remains investigational and may not reach routine clinical practice for years yet.

One question is whether the desensitization shown in the studies will produce a truly permanent tolerance to the food off treatment, Burks told attendees at a separate session at the conference.

All the immunotherapy studies show that threshold for an allergic reaction rises while on treatment, albeit with large variability among individuals in the degree of improvement, he noted.

In the study Keet presented, “after 18 months of therapy with oral immunotherapy, most subjects are desensitized but not truly tolerant,” she cautioned.

The study included 30 children ages 6 to 16 who could tolerate a median of only 100 mg (less than half a teaspoon) of milk at baseline on food challenge.

The entire study group began on sublingual immunotherapy and then were randomized to either continued daily sublingual dosing, escalated to reach 7 mg (about 1/20th of a teaspoon) of a milk extract liquid held in the mouth for a few minutes before swallowing — or to switch to daily oral immunotherapy with a goal of 1,000 mg or 2,000 mg of a nonfat dry milk powder swallowed immediately.

After 15 months of maintenance therapy, eight of the nine oral immunotherapy-group kids who passed the full desensitization food challenge and stopped daily treatments remained tolerant of milk after one week off therapy, as did the one child in the sublingual group who passed the food challenge at 15 months.

After six weeks off maintenance, only five in the oral therapy group and one in the sublingual group continued to be able to drink a glass of milk without reaction (P=0.23).

This suggested most kids wouldn’t be truly tolerant after 15 months at the doses tested, Keet noted.

However, even those who failed the challenges reacted at a higher dose threshold than before, she told the audience. the lowest level tolerated at six weeks off oral immunotherapy was 2,540 mg — far above what even the most tolerant child in the study could handle at baseline.

Immunoglobulins, skin prick testing, and other mechanistic studies affirmed greater response with oral immunotherapy than with sublingual immunotherapy, although without evidence of intrinsic basophil desensitization.

Keet reemphasized, though, that despite the promising results, more study is needed to translate the results to the clinic.

Keet reported having no conflicts of interest to disclose.

Burks reported consulting for McNeil Nutritionals and Novartis; being on an advisory board or expert panel for Nutricia and Dannon co. Probiotics; being a minority stockholder in Allertein and Mast Cell; and recieving research funding from the NIH, Food Allergy Initiative, Food Allergy and Anaphylaxis Network, Food Allergy Project, and the Wallace Research Fund.

Wood reported advisory board and grant relationships with the Food Allergy and Anaphylaxis Network and the NIH.

Sampson reported being a shareholder with Herbal Springs and consultant with Genentech.