November 27, 2017
DBV Technologies announced positive topline results from the phase III REALISE (REAL Life Use and Safety of EPIT) trial. The REALISE double-blinded period compared the safety of treatment with Viaskin Peanut 250µg versus placebo for six months. REALISE was a multicenter, randomized, double-blinded, placebo-controlled study designed to generate safety data after six months of blinded treatment in 393 patients and assess the use of Viaskin Peanut 250mcg in routine medical practice. At the six-month time point, 383 patients in both the placebo and active arms continued in the open-label portion of the study, which will monitor patients for a total of 36 months of active treatment. The REALISE trial met its primary objective, demonstrating that Viaskin Peanut was well-tolerated with no new or unexpected adverse events. Based on preliminary analysis, a similar safety profile was observed in all patients included in the trial, regardless of history of severe anaphylaxis. The safety data reported complete the FDA safety database requirement for the Viaskin Peanut program in children 4 to 11 years of age. Results from this study, in addition to data from the PEPITES phase III efficacy and safety trial, will form the basis for planned regulatory discussions in the U.S., Europe and other countries for use of Viaskin Peanut in this patient population.
April 3, 2017
Glenmark Pharmaceuticals issued results of a phase III trial of GSP 301, an investigational fixed-dose combination of mometasone furoate (25mcg) and olopatadine hydrochloride (665mcg), administered twice-daily as a nasal spray being studied for the treatment of seasonal allergic rhinitis. This U.S.-based trial was a four-arm, double-blind, randomized, parallel group, active and placebo-controlled study that enrolled 1,176 adults and adolescents 12 years of age and older for 14 days of twice daily treatment with GSP 301, mometasone (a corticosteroid), olopatadine (a histamine H1-receptor agonist) or placebo. All trial arms utilized the same vehicle and nasal spray delivery system. The primary endpoint was change from baseline in average morning and evening patient-reported 12-hour reflective Total Nasal Symptom Score (rTNSS). Secondary endpoints include safety and tolerability. In the trial, treatment with GSP 301 demonstrated statistically significant and clinically meaningful improvement from baseline in average morning and evening patient-reported rTNSS, compared to placebo (p<0.001), olopatadine (p=0.028) and mometasone (p=0.019). All investigational treatments administered in the trial were well-tolerated and showed no meaningful differences in reported adverse events (AEs) across study arms. The most common AE occurring in at least 2% of patients was dysgeusia.
March 13, 2017
Aimmune Therapeutics released results of a phase III trial of AR101 for desensitization of subjects with peanut allergy. Of those enrolled, 457 patients (78%) were reactors who experienced dose-limiting symptoms in the DBPCFC at or before the 100mg dose (median=44mg cumulative amount of peanut protein); 116 subjects (20%) were “non-reactors” who consumed all 144mg in the DBPCFC with only mild symptoms or no symptoms at all; 10 subjects (2%) reacted to placebo. Reactors demonstrated higher baseline peanut-specific IgE (psIgE) and Ara h2-specific IgE levels and larger peanut skin prick test (SPT) wheal diameters than non-reactors, and psIgE appeared to provide the greatest utility to discriminate between reactors and non-reactors. The median psIgE in reactors was 70.2 kUA/L, compared with 5.3 kUA/L in non-reactors (a threshold psIgE of 19.25 kUA/L showed the greatest sensitivity and specificity for predicting reactors). Sensitivity to peanut and severity of symptoms during screening DBPCFCs were not closely linked, and neither was associated with baseline immune parameters or age.
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 14, 2016
Aimmune Therapeutics issued results of a phase II trial of AR101 for peanut allergy. Forty patients completed 12 weeks of post–up-dosing maintenance therapy at a daily dose of 300mg of AR101. Those patients were then administered a double-blind, placebo-controlled food challenge (DBPCFC), in which 100%, 90% and 60% tolerated cumulative amounts of peanut protein of 443 mg, 1,043mg and 2,043mg, respectively (corresponding to 85%, 77% and 51% on an intent-to-treat basis). Patients who passed the highest challenge level demonstrated protection against a challenge equivalent to seven or eight peanuts. ARC002 is the open-label follow-on study to Aimmune’s ARC001 phase II trial. In ARC002, all 26 patients who received placebo in ARC001 crossed over to active treatment. Over a period of approximately 22 weeks, 21 of the 26 patients completed up-dosing to reach a daily dose of 300mg of AR101, at which point they underwent a DBPCFC. Patients then continued on a dose of 300mg of AR101 per day for a further 12 weeks of maintenance before undergoing a final DBPCFC. Also, 21 patients who received active treatment in ARC001 entered ARC002 and continued to receive 300mg of AR101 per day for the additional 12 weeks before the final DBPCFC. Aimmune’s phase III PALISADE trial of AR101 for treatment of peanut allergy is now enrolling patients in the U.S., Canada and nine countries in the European Union.
October 12, 2015
DBV Technologies has announced results
of Viaskin Peanut for peanut allergy. OLFUS
is an ongoing, open-label, follow-up study
to VIPES, the company’s phase IIb clinical
trial with Viaskin Peanut. OLFUS enrolled
171 subjects who previously had received either
placebo or one of three 12-month dose
regimens administered during VIPES. During
the first year of OLFUS, patients were to
receive a daily application of Viaskin Peanut
50μg, Viaskin Peanut 100μg or Viaskin Peanut
250μg for 12 months. Baseline response
levels in OLFUS were based on the results
of the last double-blind, placebo controlled
food challenge (DBPCFC) in VIPES, and adjusted
by the number of patients enrolling
in OLFUS. As in VIPES, a responder in the OLFUS
trial was defined as a subject who could
reach a peanut protein eliciting dose equal
to or greater than 1,000mg peanut protein
during the 12-month DBPCFC or a subject
with a ≥10-fold increase of the eliciting dose
compared to the initial eliciting dose after
12 months of treatment. Patients enrolled
in OLFUS who received placebo in VIPES
were analyzed separately from subjects who
initially received Viaskin Peanut. During the
first 12 months of OLFUS, no drug-related
epinephrine use or serious adverse events
(SAEs) due to Viaskin Peanut were reported.
The study’s median compliance rate, which
was maintained at 96%, also was consistent
with previously reported results. A preliminary
analysis of the OLFUS data showed
that 12 additional months of therapy with
Viaskin Peanut 250μg increased the number
of patients benefiting from treatment to
70% in OLFUS from 50% in VIPES, with 80%
of children (ages 6 to 11 at entry in VIPES)
responding to therapy after 24 months.
Patients who received placebo for one year
in VIPES and received Viaskin Peanut for 12
months in OLFUS showed a 50% response
rate, which was consistent with findings
from VIPES. DBV expects to launch its phase
III Viaskin Peanut trial at 35 sites in North
America, Australia, Ireland and Germany
in the fourth quarter. DBV also is in the
development process for other Viaskin treatments,
such as its treatment currently being
trialed for milk.
June 15, 2015
Aimmune Therapeutics reported results of a phase II study of AR101 for the treatment of peanut allergy. The study, conducted at eight U.S. sites, evaluated 23 patients ages four to 21 who failed a double-blind, placebo-controlled food challenge of less than or equal to 100mg of peanut protein. The randomized, double-blind, placebo-controlled study had 55 patients in the intent-to-treat population, with 29 in the active group and 26 in the placebo group. The active arm had six early discontinuations due to gastrointestinal side effects and compliance issues. All patients who completed the active treatment regimen met the primary endpoint of tolerating a cumulative amount of peanut protein of at least 443mg, compared to five of 26 patients receiving placebo (p≤0.0001). Additionally, 18 of 23 patients who completed the active treatment regimen tolerated a cumulative amount of peanut protein of at least 1,043mg, compared to zero of 26 patients receiving placebo (p≤0.0001). AR101 has been granted Fast Track designation by the FDA. Aimmune Therapeutics plans to initiate a phase III registration trial of AR101 in children and adults.
September 29, 2014
DBV Technologies has reported results
of a phase IIb trial of Viaskin Peanut in peanut
allergic patients. In the double-blind,
placebo-controlled, multicenter trial, 221
patients highly allergic to peanut were randomized
to either a 50μg, 100μg or 250μg peanut
protein dose of Viaskin Peanut versus placebo.
The trial was prospectively organized across
the three dose levels with two patient strata
composed of three different patient age groups:
children (113 subjects ages 6-11) for the first
stratum; and adolescents (73 subjects ages
12-17) plus adults (35 subjects ages 18-55)
for the other stratum. All patients received a
daily application of the Viaskin Peanut patch
over a 12-month treatment period. A total of
56 patients were randomized to the Viaskin
Peanut 250μg dose. In this arm, 50% of
patients responded, compared to 25% in the
placebo group, showing statistical significance
(p=0.0108). Adolescents showed a trend toward
efficacy, showing a response rate of 38.9%
in the active arm v. 22.2% in the corresponding
placebo group. A statistically significant
improvement in the adolescents’ ability to
consume peanut protein also was observed, as
the LS mean in change of CRD versus placebo of
this subgroup was 276mg (p=0.047). The IgG4
increase observed in adolescents, a 3.3 fold increase
over 12 months, suggests the beginning
of a successful desensitization process.
July 5, 2004
Dynavax Technologies and UCB Pharma have reported positive results of their phase I pediatric trial of AIC, their investigational ragweed allergy vaccine. Results have indicated that the drug is well tolerated in children and adolescents. The dose-escalating, open-label study enrolled 24 children between the ages of 9 and 17, all of whom had documented ragweed allergy; subjects were divided into three dosing cohorts, which each received increasing doses of AIC. Overall safety and tolerability were excellent, with only minor, localized, injection-site reactions reported and no serious adverse incidents. Based on these data, the companies announced plans to extend their clinical investigations into the use of AIC as a prophylactic against ragweed-allergy-induced sequelae, including asthma and chronic sinusitis.