Allergies & Asthma
September 12, 2016
AstraZeneca reported results of a phase II study of adding benralizumab to the standard-of-care for severe asthma. The WINDWARD program in asthma is made up of six phase III trials, including SIROCCO, CALIMA, ZONDA, BISE, BORA and GREGALE. WINDWARD evaluated a total of 3,068 patients in 798 sites across 26 countries. The two pivotal trials, SIROCCO and CALIMA, are randomized, double-blind, parallel-group, placebo-controlled trials designed to evaluate the efficacy and safety of a regular, subcutaneous administration of benralizumab (fixed 30mg dose) for up to 56 weeks in exacerbation-prone adult and adolescent patients 12 years of age and older. A total of 2,511 patients (1,205 in SIROCCO and 1,306 in CALIMA) currently receiving standard-of-care medicine (including high-dosage inhaled corticosteroids and long-acting beta 2 agonists [ICS/LABA]) were randomized globally and received either benralizumab 30mg every four weeks; benralizumab 30mg every four weeks for the first three doses followed by 30mg every eight weeks; or placebo. All benralizumab doses were administered via subcutaneous injection using an accessorized pre-filled syringe. The SIROCCO and CALIMA trials evaluated the effect of two dosing regimens of benralizumab 30mg administered in four-week and eight-week regimens as add-on therapy to standard-of-care medicine across primary and key secondary endpoints. Results showed reductions in the annual rate of asthma exacerbations (up to 51%); improvement in lung function (change in FEV1 of up to 159 mL), which was seen at four weeks after the first benralizumab dose and sustained throughout the treatment period; improvement in asthma symptoms, such as wheeze, cough, chest tightness and shortness of breath. The data from the SIROCCO and CALIMA trials will be included in regulatory submissions for benralizumab that are planned for the U.S. and EU later in 2016.
May 2, 2016
ALK issued results of a phase III trial of Acarizax for house dust mite (HDM) allergic asthma. The randomized, double-blind, placebo-controlled trial enrolled 834 adult patients. The trial was conducted at 109 sites in 13 European countries and forms part of ALK’s ongoing clinical development program for Acarizax, which has recently been approved in 11 European countries and where it is currently being launched. Patients were treated daily with either a 12 SQ-HDM or a 6 SQ-HDM dose, or with placebo in addition to inhaled corticosteroids (ICS) and short-acting beta-agonists (SABA). After a period of treatment varying between seven and 12 months, daily ICS use was reduced by half for three months and subsequently withdrawn completely for another three months for patients who did not experience an asthma exacerbation. The trial showed that 12 SQ-HDM (the dose approved in the E.U.) significantly reduced the risk of a moderate or severe asthma exacerbation relative to placebo with a hazard ratio (HR) of 0.66, corresponding to a 34% risk reduction. This included a 36% reduction in risk of nocturnal awakening or increase in daily symptoms (HR: 0.64); a 48% reduction in the risk of increased use of SABA treatments (HR: 0.52); and a 42% reduction in the deterioration of lung function (HR: 0.58).
March 9, 2015
Teva Pharmaceutical Industries released
results of two replicate, 52-week, phase III
global studies of reslizumab for asthma. In
the two double-blind studies, a total of 953
patients with moderate to severe asthma
and elevated blood eosinophil levels were
randomized to receive either intravenous
reslizumab (3mg/kg) (n=477) or placebo
(n=476) every four weeks for one year.
Results demonstrated patients receiving
reslizumab achieved reductions in clinical
asthma exacerbations (study 1 RR 0.50
[95%CI 0.37, 0.67], study 2 RR 0.41 [95%CI
0.28, 0.59], both P<0.0001) v. placebo. Lung
function improved by the first assessment
at week four, and was maintained for one
year in both studies (change in FEV1 over
52 weeks was 0.126 L, P<0.0001 and 0.090
L, P=0.006). Significant improvements from
baseline over 52 weeks were observed in
Asthma Quality of Life Questionnaire scores
(0.302, P=0.0004 and 0.234, P=0.0052),
Asthma Control Questionnaire (-0.255,
P=0.0002 and -0.242, P=0.0003) and Asthma
Symptom Utility Index (+0.061 [P<0.0001];
+0.036 [P=0.0011]). Common adverse
events in the reslizumab treatment group
were similar to placebo; two anaphylactic reactions
in the reslizumab arm were reported
that resolved with treatment at the study
site. Regulatory submissions for reslizumab
are planned for the first half of 2015.
March 2, 2015
Boehringer Ingelheim released results of
five phase III trials of tiotropium delivered via
Respimat inhaler for treatment of mild, moderate
and severe asthma in subjects who continue to
experience symptoms despite the use of maintenance
therapies. The studies included in these
analyses were double-blind, placebo-controlled,
parallel-group trials in adult patients. A total of
3,480 patients were randomized for the five trials
to receive tiotropium 5mcg, 2.5mcg or placebo in
addition to including inhaled corticosteroids with
or without long-acting beta agonists. Three criteria
were used to determine whether or not a patient
had allergies: total serum immunoglobulin E
(IgE, < or =430mcg/L [equivalent to 179.2 IU/L]),
blood eosinophils (< or =0.6×109/L) or investigator
judgment (No/Yes). Patients were permitted
to receive additional background therapy, which
varied from trial to trial, and included treatments
such as antihistamines, anti-allergic agents, nasal
steroids and omalizumab. The adverse event (AE)
data presented is pooled from the five phase III
trials in adults. The most commonly reported AEs,
by preferred term, from the pooled analyses were
asthma, bronchitis, decreased peak expiratory
flow rate, headache, nasopharyngitis and upper
respiratory tract infection.
September 8, 2014
Teva Pharmaceutical Industries reported
positive results in two phase III trials
of reslizumab for clinical asthma exacerbations
(CAE) compared to placebo in patients
with inadequately controlled, moderate to
severe asthma with elevated levels of blood
eosinophils. The two pivotal phase III studies
involved 953 patients across 232 medical
centers worldwide, including the U.S., E.U.
and the Far East. These new data are from
two global, phase III, 12-month, randomized,
double-blind, placebo-controlled, parallel-
group studies evaluating the efficacy
and safety of intravenously administered
reslizumab (3mg/kg) once every four weeks,
compared to placebo in asthma patients
(ages 12-75 with elevated blood eosinophils)
inadequately controlled by standard
of care therapy. In both trials, reslizumab
treatment showed both clinically relevant
and statistically significant reductions in
the frequency of CAE compared to placebo
(50% and 60% respectively, p<0.0001 for
both). This initial set of results shows the
adverse event profile of reslizumab was
comparable to placebo in both trials. The
incidence of common AEs (>5%) was consistent
with those seen in a moderate to severe
asthma population, the most frequent being
upper respiratory tract infections, asthma
and headache. The ongoing development
of a subcutaneous formulation is expected
to be submitted for approval in the second
half of 2017.
December 16, 2013
GlaxoSmithKline and Theravance issued
results of a phase III trial of fluticasone
furoate “FF”/vilanterol “VI” for the treatment
of adult asthma. The study was
a 12-week, randomized, double-blind,
parallel-group, multicenter study to assess
the efficacy and safety of FF/VI200/25mcg
inhalation powder, FF/VI100/25mcg
inhalation powder and FF100mcg inhalation
powder, evaluating 990 patients with
moderate to severe persistent asthma. The
primary endpoint was weighted mean
serial forced expiratory volume in one
second (FEV1) at the end of the 12-week
treatment period. The primary comparison
was FF/VI100/25mcg versus FF 100mcg.
For the pre-specified primary endpoint
of 0-24-hour weighted mean FEV1,
FF/VI 100/25mcg demonstrated a statistically
significant improvement in lung
function compared with FF 100mcg
(108ml, 95% CI 45, 171 p<0.001) at the
end of the 12-week treatment period. In
patients receiving FF/VI 200/25mcg, an
additional improvement of 24ml (95%
CI -37, 86) was observed when compared
with FF/VI 100/25mcg. These results will
inform GSK’s discussions with the FDA on
the regulatory requirements of an asthma
indication for FF/VI in the U.S.
November 18, 2013
Anergis issued results of a phase IIb study
of AllerT for the treatment of birch pollen
allergies. In the placebo-controlled, doubleblind,
multicenter trial, 240 patients from 24
European trial centers were randomized to
receive five pre-seasonal injections of AllerT
50μg, AllerT 100μg or placebo over a period
of two months between November 2012 and
March 2013. Allergen-specific IgG4 antibody
blood levels were similar in all three groups
before treatment. Four weeks after completion
of treatment and prior to the birch
pollen season, the IgG4 levels were similarly
increased in both AllerT dose groups by a factor
of about 20 compared to baseline and to
placebo (p < 0.0001). During the subsequent
birch pollen season, the IgG4 levels remained
similarly elevated in both dose groups, showing
that a plateau of IgG4 had been reached.
By contrast, IgG4 levels remained unchanged
in the placebo group during treatment and
during the pollen season.
August 29, 2011
Verona Pharmaceuticals issued results from a phase II trial of RPL554 for the treatment of mild asthma. This blind, randomized, placebo-controlled trial enrolled 12 subjects who received daily doses of RPL554 for six days. Efficacy on lung function was based on the standard measure of FEV1 (Forced Expiratory Volume in 1 sec). RPL554 successfully sustained bronchodilator actions throughout the treatment period. Identical bronchodilator responses were seen after one, three and six days of treatment. There was no evidence of RPL554 accumulation in plasma over the six days. There were no safety concerns, although there was a minor increase in heart rate at day six.
May 9, 2011
ISTA Pharmaceuticals issued results from a phase II trial of bepotastine besilate nasal spray for seasonal allergic rhinitis. This randomized, multi-center, double-masked, placebo-controlled, dose-ranging trial enrolled 600 subjects with allergic rhinitis caused by Mountain Cedar pollen. The subjects received one of three concentrations of bepotastine besilate nasal spray or placebo twice a day for two weeks. All three concentrations of bepotastine besilate nasal spray showed statistically significant improvements compared to placebo for nasal and ocular symptoms following exposure to Mountain Cedar pollen during the peak season for this allergen. These improvements were seen on day one of therapy and were sustained through the two-week treatment period. Safety data demonstrated bepotastine besilate was well-tolerated as a nasal spray, with an adverse event profile similar to placebo.
February 14, 2011
Teva released positive results from a phase III trial of Qnaze, their nasal aerosol corticosteroid for perennial allergic rhinitis. The randomized, double-blind, placebo-controlled, parallel-group clinical study enrolled 470 subjects, aged 12 years and older, who received Qnaze nasal aerosol 320 mcg or placebo once-daily for six weeks. The primary endpoint, the change from baseline in the average morning and evening subject-reported reflective Total Nasal Symptom Score (rTNSS), was reached with statistical significance over placebo (p<0.001). The change in instantaneous TNSS (iTNSS), a secondary endpoint, was also significantly greater versus placebo. In addition, for both of these measures, all four individual nasal symptom scores of runny nose, nasal congestion, nasal itching and sneezing demonstrated significant improvement versus placebo. Qnaze was well tolerated.
October 11, 2010
ISTA Pharmaceuticals reported positive results from a phase I/II trial of bepotastine besilate nasal spray for the treatment of seasonal allergic rhinitis. This double-masked, randomized, placebo-controlled, parallel-group study enrolled 82 subjects in Canada. The subjects were exposed on multiple occasions in an Environmental Exposure Chamber to a high aerosol concentration of a common seasonal allergen to which they were sensitive. They graded their individual symptoms at select time intervals prior to and following a single dose or one week of dosing with one of three bepotastine besilate nasal spray doses or placebo. The highest two concentrations of bepotatine besilate nasal spray tested showed statistically significant improvement compared to placebo in reducing total nasal symptoms. These reports were consistent for both instantaneous and reflective experiences of their total nasal symptoms. Statistically significant improvements also were seen for all individual nasal symptoms, with the most rapid improvement seen for drug-related reductions in sneezing and nasal itching. Adverse events were similar across all treatment groups.
September 27, 2010
Cytos released positive results from a phase II trial of CYT003-QbG10 for the treatment of persistent allergic asthma. This randomized, placebo-controlled trial enrolled 63 subjects with persistent allergic asthma requiring maintenance therapy with inhaled corticosteroids. The subjects were randomized to treatment with either CYT003-QbG10 (7 weekly to biweekly subcutaneous injections or placebo as add-on treatment for four weeks. At week four, they entered a corticosteroid reduction phase, where the dose was initially reduced by 50% for the following four weeks and completely withdrawn at week eight if clinical stability allowed. Under CYT003-QbG10 treatment the fraction of patients whose asthma was well controlled increased from 42% pre-treatment to 67% post-treatment despite corticosteroid withdrawal, while on placebo this fraction decreased from 40% to 33% (p≡0.008). At week 12, day and nighttime asthma symptoms had decreased by 33% under QbG10 treatment, while they had increased by 29% under placebo (p≡0.01). Use of relief medication doubled (+106%) in the placebo group, while it remained stable in the QbG10 group (-4%) (p≡0.01). The forced expiratory volume in one second FEV1 at week 12 had decreased on placebo by an average of 251 ml (-8.4%) while it remained stable on QbG10 treatment (-18.5 ml, -0.6%) (p≡0.01). In addition, anti-inflammatory effects of treatment were demonstrated by a significant reduction in blood eosinophils under QbG10 therapy versus placebo (p≡.043). Treatment was safe and well tolerated.
May 24, 2010
Revotar released positive results from a phase IIa trial of bimosiamose for the treatment of ozone-induced airway inflammation. This double-blind, placebo controlled, randomized cross-over study enrolled 18 healthy, non-smoking ozone-responsive subjects able to produce sputum. Each subject received nebulized Bimosiamose solution or placebo twice daily for four consecutive days in two subsequent periods separated by a wash-out phase (cross-over). Treatment was followed by ozone challenge and subsequent collection of induced sputum. The primary endpoint was the difference of neutrophil counts between the bimosiamose and placebo treatment arms. Compared to placebo, the compound demonstrated a broad and significant anti-inflammatory effect on cellular and non-cellular sputum parameters. Inhalation of Bimosiamose was safe and well tolerated.
March 23, 2009
Cydex released positive results from a phase II trial of CDX-313 nasal spray for the treatment of seasonal allergic rhinitis (SAR). This randomized, double-blind, three-way cross-over study enrolled 108 subjects with SAR. The subjects received CDX-313 nasal spray (Budesonide + Azelastine), Rhinocort Aqua + Astelin Nasal Spray or placebo nasal spray while in an environmental exposure chamber. Relief of all nasal symptoms as measured by the Total Nasal Symptom Score (TNSS) was significantly greater than placebo from 20 minutes following administration until the session end (10 hours) for both CDX-313 and Rhinocort Aqua/Astelin (p<0.0001). Onset of action of relief from itchy nose and sneezing were significantly faster at 10 minutes for CDX-313 compared to Rhinocort Aqua/Astelin. Relief of all eye symptoms as measured by the Total Ocular Symptom Score (TOSS) was significantly greater than placebo from 40 minutes following administration until the session end (10 hours) for both CDX-313 and Rhinocort Aqua/Astelin (p<0.0001). CDX-313 provided the same or greater numerical TOSS relief than Rhinocort Aqua/Astelin and longer-lasting relief of red/burning eyes and itchy eyes.
November 17, 2008
Genentech and Novartis issued positive results from a phase III trial of Xolair for the treatment of allergic asthma. This double-blind, randomized placebo-controlled study enrolled 628 pediatrics, aged six through 11, with moderate-to-severe allergic asthma uncontrolled despite inhaled corticosteroid (ICS) therapy. The subjects were randomized to receive Xolair therapy or placebo, added on to their current ICS therapy. The study comprised a 24-week fixed-dose ICS phase, followed by a 28-week phase in which ICS doses could be reduced, and a 16-week safety follow-up period. The study met its primary endpoint; at 24 weeks the subjects treated with Xolair demonstrated a 31% reduction in clinically significant asthma exacerbations compared to those treated with placebo. After a year of treatment, subjects treated with Xolair demonstrated 43% fewer clinically significant asthma exacerbations than those receiving placebo. Adverse events were similar between groups and most were mild or moderate.
August 4, 2008
Cytos issued positive results from two phase II trials of CYT003-QbG10 for the treatment of allergies. The first study, 08, was a randomized, double-blind, placebo-controlled design and enrolled 80 subjects with house dust mite and /or cat allergy. The subjects received six ascending dose injections of CYT003-QbG10 (300-900 ug) or placebo. Cyt003-QbG10 significantly reduced rhinoconjunctivitis symptoms in daily life compared to placebo (p=0.008). The CYT003-QbG10 treatment group mean total rhinoconjunctivitis symptom score had fallen from 9.3 points pre-treatment to 3.6 points post-treatment (-61%), whereas for the placebo group a reduction from 9.2 points pre-treatment to 6.3 points post-treatment (-32%) was observed. In addition, the allergen tolerance as measured in the conjunctival provocation test was improved after CYT003-QbG10 treatment compared to placebo, although the improvement wasnt significant (p=0.06). The second study, (04), was also a randomized, double-blind, placebo-controlled design and enrolled 93 subjects with house dust mite allergy. The subjects received a combination of 300 ug QbG10 with an approved allergen extract, dubbed CYT005-AllQbG10 or the allergen extract alone. Reductions of the mean total rhinoconjunctivitis symptom score were observed (-54% for CYT005-AllQbG10 and -51% for the allergen extract), however this was not significant. The conjunctival provocation test showed a trend in favor of CYT005-AllQbG10 (p=0.11). Treatment was well tolerated in both trials. Based on the results, Cytos plans to commence a phase IIb trial of CYT003-QbG10 monotherapy in the fourth quarter of 2008.
March 31, 2008
MAP Pharma released positive results from a pharmacokinetic trial of Unit Dose Budesonide (UDB) for the treatment of asthma. This randomized, open label, cross-over study enrolled thirty two adult subjects with mild to moderate asthma. A 0.135 mg dose of UDB was compared to a 0.25 mg dose of conventional nebulized budesonide given twice daily, and a 0.25 mg dose of UDB was compared to a 0.5 mg dose of conventional nebulized budesonide given twice daily. Data showed that compared to conventional nebulized budesonide, UDB demonstrated faster times to maximum blood concentrations and had similar maximum blood concentrations. In addition, the nebulization time for UDB in this population was shorter than for the conventional nebulized budesonide product. Treatment was well tolerated, with serious adverse events reported. A phase III trial of Unit Dose Budesonide is currently underway.
May 21, 2007
Cytos announced positive results from a phase IIa trial of CYT003 -QbG10 for the treatment of allergic rhinitis due to house dust mite allergy. This double-blind, placebo controlled trial enrolled 40 subjects who received CYT003-QbG10 monotherapy, CYT003-QbG10 combined with a low dose of house dust mite allergen extract (CYT005-AllQbG10), allergen extract alone and placebo. Both formulations of CYT003-QbG10 were safe and well tolerated. Efficacy results revealed a statistically significant increase in the median allergen tolerance against baseline in the CYT003-QbG10 and CYT005-AllQbG10 treatment arms (p-value <0.05). Based on the data the Cytos plans to test higher doses of CYT003-QbG10 monotherapy in future clinical trials.
May 14, 2007
Inspire issued positive results from a phase II trial of epinastine nasal spray for the treatment of seasonal allergic rhinitis. This randomized, double-blind comparison trial enrolled 569 subjects with a history of seasonal allergic rhinitis to mountain cedar pollen. Subjects received epinastine at one of two doses, 0.05% or 0.1%, for 14 days. The primary endpoint was improvement from baseline in the total nasal symptom score (TNSS). The higher dose group, 0.1%, reached statistical significance for this endpoint compared to placebo (p less than or equal to 0.05). Statistical significance was not reached for the 0.05% group. The 0.1% epinastine group also reached statistical significance in the secondary endpoints of non-nasal symptom score and total symptom score, when compared to placebo (p less than or equal to 0.05). Based on these results, Inspire plans to meet with the FDA to determine the future course of action for epinastine.
July 4, 2005
Cambridge Antibody Technology has reported positive results of a phase I trial of CAT-354, their monoclonal antibody for the treatment of asthma. Trial data met primary safety and pharmacokinetic endpoints, with no serious adverse events reported, a positive overall adverse event profile, and an absorption and elimination profile in line with expectations from preclinical models. This double-blind, placebo-controlled single-escalating-dose study enrolled 34 patients with mild asthma. The company announced plans to initiate their second trial of the drug, a multiple-dose allergen-challenge clinical pharmacology study, in Q4 2005.
May 30, 2005
Sanofi-Aventis announced positive results of a phase III trial of their inhaled corticosteroid Alveso (ciclesonide) for the treatment of asthma at the 101st International Conference of the American Thoracic Society. Results from the study demonstrated that administration of the drug allowed a significant portion of subjects in both the low dose (29.8%; p=0.0386) and high dose (31.3%; p=0.233) Alvesco treatment groups were able to completely discontinue oral corticosteroids, vs. 11.1% for placebo. Secondary evaluations indicated that both doses of Alvesco produced significant reductions in mean overall oral corticosteroid dose (-47.39%, p= 0.0003; -62.54%, p=0.0001), and overall daily oral dose (-5.97 mg/day, p=0.0008; -8.00 mg/day, p= 0.0001). This multinational, multicenter, randomized, double-blind, placebo-controlled study enrolled 141 adult asthma patients currently taking oral corticosteroids, who received one of two doses of Alvesco (320 mcg or 640 mcg) or placebo twice daily for 12 weeks.
January 24, 2005
ALK-Abello has reported positive preliminary results of their “GT-07” trial of their sublingual grass-pollen immunotherapy tablet, for the prevention of rhinoconjunctivitis (hay-fever). Trial data met their primary efficacy endpoint, producing a 37% reduction in symptoms of rhinoconjunctivitis and a 41% reduction in the need for additional medication, vs. placebo. The drug was also found to be safe and well tolerated. This double-blind, placebo-controlled, multi-centre study enrolled 114 patients with moderate-to-severe rhinoconjunctivitis and grass pollen induced mild-to-moderate asthma in Sweden and Denmark. Subjects were randomized to receive either the tablet or placebo once daily for at least 10 weeks.
Genentech has reported positive final results of a phase III extension study of their approved humanized monoclonal antibody Raptiva (efalizumab), for the treatment of moderate to severe plaque psoriasis. Results indicated that the drug produced demonstrated improved efficacy at 24 weeks vs. 12 in a number of clinical outcomes, including improvements in the portion of subjects achieving PASI-75 severity score improvement levels (43.8% vs. 26.6%), PASI-50 (66.6% vs. 58.5%). Furthermore, the percentage of patients who achieved a sPGA rating of minimal or clear increased from 25.7% at 12 weeks to 35.9% at 24, and the mean percentage of improvement in all patient-reported outcomes was maintained at week 24. Overall reported adverse events also declined during the extension (from 80.4% to 63.2%). This 12-week, 516-patient open-label extension followed a 12-week, 556-patient, double-blind, placebo-controlled parallel-group study, which investigated once-weekly subcutaneous dosing of 1 mg/kg Raptiva or placebo.
Valeant Pharmaceuticals has issued positive results of a phase II trial of its oral guanosine analog Viramidine, for the treatment of Hepatitis C. Preliminary analysis of trial data has indicated that the trial met its primary efficacy endpoint, demonstrating non-inferiority of Sustained Viral Response (SVR) for the 600 mg. BID dose of Viramidine, compared with ribavirin (an approved treatment), at both the end of treatment (24 or 48 weeks) and after an additional 24 week follow-up. Furthermore, the drug produced a significantly lower rate of anemia than the approved therapy (4% vs. 27%; p<0.001), and incidence of all other adverse events was similar between drugs. This active-controlled proof of concept study enrolled a total of 180 treatment-naïve patients with chronic HCV, who were randomized to receive one of three BID regimens of Viramidine (400 mg, 600 mg, or 800 mg) or standard therapy with ribavirin (1,000/1,200mg daily). Subjects were treated for 24 or 48 weeks, based on viral genotype analysis, and then enrolled in a 24 week extension study. Based on these results, Valeant has announced plans to use the 600 mg BID regimen of the drug in phase III trials.