July 25, 2016
Ultragenyx Pharmaceutical reported results of a phase III study of recombinant human beta-glucuronidase (rhGUS, UX003) for the treatment of Mucopolysaccharidosis 7 (MPS 7, Sly syndrome). The randomized, placebo-controlled, blind-start clinical study, conducted at four sites in the U.S., was designed to assess the efficacy and safety of rhGUS in 12 patients between 5 and 35 years of age. Patients were randomized to one of four groups. Patients were dosed with 4mg/kg of rhGUS every other week for up to a total of 48 weeks, and all groups received a minimum of 24 weeks of treatment with rhGUS. The study met its primary endpoint of reducing urinary GAG (dermatan sulfate) excretion after 24 weeks of treatment, demonstrating a reduction from baseline of 64.8 percent (p<0.0001). The study provides evidence of clinical improvement with rhGUS treatment. The Multi-domain Responder Index (MDRI) score at 24 weeks of treatment, a secondary endpoint, demonstrated an overall mean improvement (±SD) of +0.5 domains (±0.80) (p=0.0527). Six of the 12 patients had an improvement in their MDRI score of +1 or more. Five patients demonstrated no worsening of this progressive disease, or an MDRI score of 0. One patient had an MDRI score of -1. The MDRI is a summation of scores from each of the following domains: the six-minute walk test (6MWT), forced vital capacity (FVC), shoulder flexion, visual acuity and the Bruininks-Oseretsky Test of Motor Proficiency (BOT-2) fine motor and gross motor function. For the 6MWT, the improvement (±SE) was 20.8 (±16.75) meters at 24 weeks of treatment based on the estimates from nine patients who had any change from baseline data. Three of these patients demonstrated an improvement of a magnitude equal or greater than the MID with increases of 65 meters, 80 meters and 83 meters at 24 weeks compared to baseline. For the fatigue scores, four patients improved at or above the MID level after 24 weeks of treatment and nine of 12 showed improvement at some point during the study. Based on these data, Ultragenyx plans to meet with the FDA and EMA this year to discuss plans to submit regulatory filings in the first half of 2017.
October 13, 2014
Erytech reported results of a phase III
study of Graspa for acute lymphoblastic
leukemia (ALL). The three-arm, controlled,
multicenter trial enrolled 80 children and
adults. The first two arms compared Graspa
to native E. Coli L-asparaginase, both in
combination with standard chemotherapy,
in a 1-to-1 randomization in patients without
prior allergies to L-asparaginase. The third
arm was an open-label assessment of Graspa
for patients who have experienced allergic
reactions related to asparaginase in their
first-line treatment. None of the 26 patients
in the Graspa arm experienced an allergic
reaction v. 12 of the 28 (42.9%) patients
treated with reference L-asparaginase in the
control group (p<001). In the Graspa group,
asparaginase levels were maintained above
100 IU/l for an average of 20.5 days with up
to two injections during the first month of
treatment (induction phase) v. 9.2 days in the
control group with up to eight injections of
reference L-asparaginase (p<001). At the end
of the induction phase, 15 patients (71.4%)
in the Graspa arm show complete remission
v. 11 patients (42.3%) in the control arm.
Erytech intends to submit an application to
the European Marketing Authorization in the
first half of 2015.
Salvat released results from two phase III
studies comparing Ciprofloxacin 0.3% plus
Fluocinolone Acetonide 0.025% Otic Solution
to the components alone (Ciprofloxacin 0.3%
otic solution and Fluocinolone Acetonide
0.025% otic solution) in the treatment of
pediatric patients with acute otitis media
with tympanostomy tubes (AOMT). The two
identical studies followed a three-arm, multi-center,
randomized, double-blind design to
compare the efficacy and safety of the combination
to that of the components alone when
administered twice a day during seven days
in children (six months to 12 years old) with
AOMT. The studies were performed in U.S.,
Canada, Europe and South Africa, with 331
patients recruited in each trial (662 patients
in total). For the primary efficacy parameter,
time to cessation of otorrhea, a significant
reduction was observed when comparing the
combination to Ciprofloxacin alone (p<0.001
in one study and p<0.05 in the other) and to
Fluocinolone alone (p<0.001 in both studies).
Results also showed sustained microbiological
cure was met in both trials by demonstrating
statistical differences between the
combination and Fluocinolone (p<0.001 in
each trial). The company plans to submit an
NDA to the FDA.
July 28, 2014
Otonomy reported results of phase III trials
of AuriPro in a combined total of 532 pediatric
patients with bilateral middle ear effusion
requiring tympanostomy tube placement. The
randomized, double-blind, sham-controlled
phase III studies enrolled subjects ages six
months to 17 years old, across approximately
60 trial sites in the U.S. and Canada. AuriPro
achieved the primary efficacy endpoint with
statistical significance (p<0.001). The primary
endpoint of the studies was the effectiveness
of AuriPro as measured by the cumulative
proportion of study treatment failures through
day 15, which is defined as the presence of
otorrhea (drainage) or use of antibiotic rescue
medication. AuriPro was well-tolerated.
July 14, 2014
Merck reported results for a phase III
study of EMEND (aprepitant) in the prevention
of chemotherapy-induced nausea and
vomiting (CINV) in pediatric cancer patients,
aged 6 months to 17 years. In the randomized,
study of 302 participants, patients receiving
emetogenic chemotherapy were randomly
assigned to receive an EMEND plus ondansetron
regimen (n=152) or a control regimen
(placebo plus ondansetron) (n=150). The
first dose of EMEND (plus ondansetron) was
administered on day one of chemotherapy,
then subsequently (without ondansetron)
later on days two and three. In the study,
51% of patients receiving the EMEND
regimen achieved the primary endpoint of
complete response in the delayed phase
of CINV, versus 26% of those in the control
group (p<0.0001). For the secondary endpoints,
66% of patients receiving the EMEND
regimen achieved a complete response in
the acute phase of CINV, versus 52% of those
receiving the control regimen (p=0.0135). In
addition, complete response in the overall
phase was higher in patients receiving the
EMEND regimen versus the control regimen
(40% v. 20%, p=0.0002). No vomiting in the
overall phase was observed in 47% v. 21% of
patients receiving the EMEND regimen compared
to the control regimen, respectively
(p<0.0001). Merck plans worldwide regulatory
submissions for EMEND, beginning in
the U.S. in the second half of 2014.
March 3, 2014
Isis Pharmaceuticals issued interim
results of an ongoing phase Ib/IIa, open-label,
multiple-dose study of ISIS-SMNRx in children
with spinal muscular atrophy (SMA). Children
were dosed intrathecally with 3mg, 6mg or
9mg of ISIS-SMNRx. The 3mg and 6mg doses
were administered on days 1, 29 and 85. The
9mg dose was administered on days 1 and 85.
Muscle function changes were measured using
the Hammersmith Functional Motor Scale-
Expanded (HFMSE). Subjects in the 3mg, 6 mg
and 9mg cohorts achieved mean increases
in HFMSE scores of 1.5, 2.3 and 3.7 points,
respectively, nine months following the first
dose of ISIS-SMNRx. Children in the 9mg cohort
achieved mean increases in HFMSE scores of 2.7
and 3.7 points three and nine months after the
first dose of ISIS-SMNRx, respectively. Isis plans to
give all children who roll over into an extension
study a maintenance dose of 12mg of ISISSMN
Rx every six months.
October 14, 2013
Versartis issued results from a phase Ib/IIa trial of VRS-317 in pre-pubertal children with growth hormone deficiency (GHD). The study is being conducted in approximately 30 U.S. pediatric endocrinology centers and will enroll up to 72 naïve-to-treatment, pre-pubertal children with GHD documented by auxologic criteria and two GH stimulation tests. VRS-317 dosing began at 0.80mg/kg, with dose increases to 1.20mg/kg, 1.80mg/kg, 2.70mg/kg, 4mg/kg and 6mg/kg (equivalent to 4.8, 7.4, 11.1, 16.7, 24.7 and 37.0mcg rhGH per kg per day taken for 30 days). 48 subjects (27M, 21F) with mean age 7.2 years were studied in six dose cohorts (eight per cohort). VRS-317 plasma concentrations reach a maximum at a mean time of three days post-dose, are proportional to dose and remain detectable for up to 30 days from a single dose in all subjects tested. Maximal changes in IGF-I SDS occur between two to 14 days after a single dose on day one. The amplitude and duration of IGF-I responses increase with increasing VRS-317 dose. The increase in average IGF-1 SDS over 30 days also was proportional to dose and sufficient to support up to once-monthly dosing of VRS-317. Importantly, the prolonged IGF-I responses do not come at the expense of over-exposure to high IGF-I levels, where only a single value of IGF-I SDS in each of two patients has exceeded +2.
September 16, 2013
Otonomy issued results of a phase Ib study of OTO-201 in pediatric patients undergoing tympanostomy tube placement (TTP) surgery. OTO-201 is a sustained-release otic formulation of ciprofloxacin. The randomized, prospective, multi-center, double blind, placebo- and sham-controlled phase Ib clinical trial enrolled 83 pediatric patients between six months and 12 years of age who required TTP surgery. OTO-201 was administered as a single intra-operative treatment for patients with bilateral middle ear effusion on the day of surgery. Two dosage strengths of OTO-201 (2% and 6%) were tested in the trial. Both OTO-201 active treatment arms showed a reduction of treatment failure of more than 60% relative to the placebo/sham group (p<0.05). OTO-201, at both doses tested, appeared to be well-tolerated. Otonomy plans to discuss these findings and next steps for clinical development at an end of phase II meeting with the FDA.
July 1, 2013
Versartis released results from a phaseIb/IIa trial of VRS-317 for the treatment of Growth Hormone Deficiency (GHD). The trial enrolled 72 naïve-to-treatment, pre-pubertal children with GHD and consisted of two stages. VRS-317 dosing began at 0.80 mg/kg, a dose shown to be safe and well-tolerated in GHD adults in a previously completed trial, with planned dose increases to 1.2mg/kg, 1.8mg/kg, 2.7mg/kg, 4mg/kg and up to 6mg/kg. The typical dose of daily rhGH in children with GHD is approximately 40mcg/kg/day. Related adverse events have been reported in 12 subjects to date and all have been mild and transient. Single doses of up to 2.7mg/kg are safe and well-tolerated. In addition, dose proportional increases in VRS-317 levels and IGF-I responses were observed, indicating the ability to select doses and dose regimens for up to once monthly dosing. The only approved growth hormone treatments require daily injections.
January 17, 2011
Enobia Pharma released positive results from a phase II trial of ENB-0040 for the treatment of juveniles with hypophosphatasia (HPP). This six-month, open label trial enrolled 13 pediatrics, ages five to 12 years, with rickets and gross motor deficits from HPP. The subjects received subcutaneous injections of either 2 mg/kg or 3 mg/kg ENB-0040 three times weekly for 24 weeks. The primary endpoint was reached, with data demonstrating a statistically significant improvement in rickets when compared with historical matched cohort controls (p≡0.002). Nine of 13 subjects enrolled (69%) and nine of 12 who completed the study (75%) achieved a substantial improvement in rickets as assessed by skeletal radiographs of the wrists and knees, compared with two of 17 (12%) historical controls.
October 4, 2010
Enobia Pharma reported positive results from a phase II trial of ENB-0040 for the treatment of juvenile hypophosphatasia. This six-month, randomized, open label, dose comparison study enrolled 13 subjects, ages five to 12 years with rickets and gross motor deficits from hypophosphatasia. The subjects received subcutaneous injections of either 2 mg/kg or 3 mg/kg ENB-0040 three times weekly for 24 weeks. The efficacy of ENB-0040 was primarily based on improvements in rickets as measured by X-rays. Data showed radiographic improvement of rickets noted as early as six weeks after starting treatment. EMB-0040 also led to improvement in muscle strength and agility over baseline, including an average improvement of 125m on six-minute walk test. In addition, amelioration of pain was reported in six of seven patients experiencing pain at baseline. Subcutaneous injections of ENB-0040 were generally well tolerated and no serious adverse events were reported.
June 28, 2010
Enobia released positive interim results from a phase II trial of ENB-0040 for the treatment of hypophosphatasia (HPP). This six-month, randomized, open label, dose comparison study enrolled 13 pediatrics with HPP between the ages of 5 and 12 years across sites in North America. ENB-0040 (2 mg/kg or 3 mg/kg) was administered as a subcutaneous injection three times weekly for 24 weeks. After 12 weeks of treatment with ENB-0040, there were marked improvements in bone mineralization and function, including increases in strength, endurance and mobility and reduction in pain.
January 21, 2008
Amgen and Wyeth issued positive results from a phase III trial of Enbrel for the treatment of moderate to severe plaque psoriasis in children and adolescents. This trial enrolled two hundred and eleven pediatric subjects with psoriasis who were initially randomized to receive twelve once-weekly weight-based doses of Enbrel (0.8 mg/kg up to the intended dose of 50 mg) or placebo. After this double-blind portion, two hundred and eight subjects entered a twenty four-week period of open-label Enbrel treatment once-weekly. At week thirty six, one hundred and thirty eight subjects were re-randomized to receive either Enbrel or placebo, to investigate withdrawal and re-treatment. The primary endpoint was at least a 75% improvement on the Psoriasis Area and Severity Index (PASI 75) at week twelve. After twelve weeks, the conclusion of the double-blind, placebo-controlled portion of the study, 57% of the subjects treated with Enbrel achieved PASI 75, compared with 11% of those treated with placebo (p less than 0.001). After twenty four weeks of open-label treatment, during which all subjects received Enbrel, PASI 75 was achieved by 68% of the subjects initially treated with Enbrel from the start of the study and 65% of those who initially received placebo. At the conclusion of the open-label treatment period (week thirty six), one hundred and thirty eight subjects were re-randomized to receive either Enbrel or placebo. During this period, the subjects who lost PASI 75 were re-treated. No rebounds or changes in the type of psoriasis were reported. Based on the results, Amgen filed a sBLA with the FDA for the use of Enbrel in this population.
August 20, 2007
BioMarin and Merck-Serono issued positive results from a phase III trial of Kuvan for the treatment of phenylketonuria (PKU). This international, randomized, placebo-controlled trial enrolled 89 subjects, aged 8 years and older, with elevated blood Phe levels. The subjects received placebo or 10 mg/kg of Kuvan daily for six weeks. They were evaluated every two weeks for changes in blood phenylalanine (Phe) levels and adverse events. The primary endpoint was to assess the efficacy of Kuvan compared with placebo for reduction of blood Phe. The secondary endpoint was to assess the safety of Kuvan compared with placebo. At baseline, subjects in the Kuvan group and placebo group had mean blood Phe levels of 843 uM/L and 888 uM/L, respectively. At six weeks, the Kuvan cohort had a mean decrease in blood Phe level of 236 uM/L (29%) compared to a mean increase of 3 uM/L (3%) in the placebo group (p<0.0001). In the subjects treated with Kuvan, 54% had a blood phenylalanine concentration below the recommended 600 uM/L level versus 23% of those in the placebo group (p=0.003). In addition, blood Phe concentrations fell by about 200 uM/L after one week in the Kuvan group, and this reduction persisted for the remaining five weeks of the study (p<0.0001). Treatment was well tolerated, with adverse events similar between the Ku
November 27, 2006
Shire reported positive results from a phase III trial of guanfacine XR for the treatment of ADHD symptoms in pediatrics aged 6 to 17. The double-blind trial enrolled 345 subjects who underwent a one week washout period, then were randomized to receive placebo or 2, 3 or 4 mg of guanfacine extended release, once daily, for eight weeks. Guanfacine XR was titrated in 1 mg increments per week, from 1 mg per day during the first week to a maximum of 4 mg daily in weeks four and five according to randomization. Guanfacine XR was then decreased at the same weekly rate starting in weeks six and seven. Treatment was well tolerated with no serious adverse events reported. The most commonly reported events included somnolence, headache and fatigue. Efficacy was based on ADHD Rating Scale (ADHD-RS-IV) measurements. The guanfacine XR treated group had an average reduction in ADHD-RS-IV total scores of 16.7 points versus 8.9 points for placebo (P < .0001). Significance was observed in all secondary endpoints as well, which included scores on various other ADHD diagnostic scales. A NDA is currently under review for guanfacine extended release.
November 22, 2004
Nabi Biopharmaceuticals reported mixed results of a phase II trial of Altastaph (Staphylococcus aureus Human Immune Globulin), for the prevention of Staphylococcus aureus infections in at-risk premature neonates. The trial met its primary safety, tolerability and pharmacokinetic endpoints, with no serious adverse events, and antibody levels believed to be protective against infections. However, the observed rate of Staphylococcal infection (3%) was considerably less than literature established baseline (5%-7%), and was not significantly different between placebo and Altastaph groups; these results thus failed to meet the secondary efficacy endpoint of a reduction in incidence of infections in neonates receiving Altastaph versus placebo. This double-blinded, placebo-controlled trial enrolled 200 very low birth-weight premature infants across 20 neonatal ICUs in the US. Subjects received one of two doses of Altastaph or placebo 14 days apart 3 to 7 days after birth. Following these results, Nabi announced plans to meet with regulators to discuss the timing and design of additional clinical studies.
August 16, 2004
Barrier Therapeutics reported results from a phase III trial investigating Zimycan, a topical antifungal ointment for the treatment of Candida-associated diaper dermatitis. Results showed that Zimycan achieved statistical significance versus vehicle ointment for all endpoints. Data showed that the average reduction in the signs and symptoms score, was 72% with Zimycan versus 25% with the vehicle ointment. More than twice the subjects treated with Zimycan reached the primary endpoint, overall cure at day 14, as compared with vehicle. The double-blind, vehicle-controlled study enrolled 236 infants at 20 sites in the U.S. and Latin America. Subjects were given Zimycan or vehicle for seven days. The study will form the basis of the filing of an amendment to Barrier's pending NDA.
July 26, 2004
BioMarin has announced positive results of a pilot study of 6R-BH4, the active component of their investigational drug Phenoptin, for the treatment of phenylketonuria (PKU). Results indicated that the drug was efficacious in mitigating PKU, reducing mean serum phenylalanine (Phe) levels by 36% at the highest dosing regimen after 7 days of treatment. Results also noted an increase in serum tyrosine levels, to which Phe is converted in normal subjects, possibly indicating that 6R-BH4 was effective in restoring normal metabolic function. The open-label study, which enrolled 20 PKU patients, was designed to test the efficacy of two sequential daily oral dosing regimens of 6R-BH4. No safety concerns were noted, and BioMarin announced plans to continue clinical development later this year.
Insmed has provided an interim update on their phase III study of SomatoKine (mecasermin rinfabate), which is being developed for children with severe short stature due to growth hormone insensitivity (GHIS). Six-month interim data analysis has shown that the drug is efficacious in treating GHIS, with a highly statistically significant increase in height velocity following once-daily injections (p<0.0001). The ongoing multi-center, open-label study was designed to investigate the safety and efficacy of SomatoKine in pre-pubescent children with GHIS. No serious adverse events were noted. SomatoKine announced that final results are expected in 2005.
November 17, 2003
Stressgen Biotechnologies reported interim results from an ongoing phase II investigating HspE7, a recombinant fusion product for the treatment of recurrent respiratory papillomatosis (RRP). Results showed that the first post-treatment interval increased 78.6% over the pretreatment interval. Data at the study half way point showed the median of all post-treatment inter-surgical intervals compared with pretreatment has increased to 95.9 days, compared to 83.1 days previously reported and 55.3 at baseline. The median interval reported predicts at least 70 fewer surgeries during the first year post- treatment. HspE7 was well tolerated with the most common side effect being mild to moderate reaction at the site of injection. Results were reported at the meeting of the Society of Ear, Nose and Throat Advances in Children held in conjunction with the American Academy of Pediatrics.
October 21, 2002
Transkaryotic Therapies reported positive results from a phase I/II trial investigating iduronate-2-sulfatase (I2S), an enzyme replacement therapy as a possible treatment for Hunter syndrome. The drug was generally well tolerated and demonstrated evidence of clinical activity. The randomized, double blind, placebo-controlled study evaluated the safety of I2S and its clinical activity in 12 subjects affected with Hunter syndrome. The data demonstrated mean reductions in glycosaminoglycan (GAG) levels, the toxic substrate that accumulates in patients with Hunter syndrome. Mean urinary GAG reductions of 41%, 51%, and 59% were observed from baseline for subjects in the 0.15 mg/kg, 0.5 mg/kg, and 1.5 mg/kg groups, respectively, compared to a 4% increase in the placebo group. I2S also demonstrated a mean reduction of mass in enlarged organs such as liver, spleen and heart. Transkaryotic Therapies believes the data from this trial support the advancement of this program into pivotal clinical testing.
July 8, 2002
Results from a 24-week, open-label extension of a phase I trial indicate that both dose levels (0.2 mg/kg and 1.0 mg/kg) of BioMarin Pharmaceutical's Aryplase continue to be well tolerated by the five subjects who have received treatment for a total of 48 weeks. Aryplase is an enzyme replacement therapy being developed for the treatment of mucopolysaccharidosis VI. In addition to the positive safety results, the 1.0 mg/kg dose continued to produce a greater sustained reduction than the 0.2 mg/kg dose in the excretion of urinary glycosaminoglycans.
July 1, 2002
Positive results were reported from double-blind and extension study portions of a phase III trial of Aldurazyme (laronidase), an enzyme replacement therapy for mucopolysaccharidosis I (MPS I). In the six-month double-blind portion, subjects treated with Aldurazyme achieved a 5.3 percentage point mean increase in pulmonary capacity (as measured by FVC) compared to placebo-treated subjects. Subjects in the Aldurazyme group also demonstrated a positive trend in endurance as measured by a six-minute walk test. All 45 MPS I subjects from the double-blind portion were enrolled in an ongoing open-label study, with placebo-treated subjects switched to also receive Aldurazyme. Results showed that the subjects who initially received Aldurazyme in the double-blind portion improved from a 19.7 meter mean increase in the six-minute walk test to a 42.9 meter mean increase after an additional six months of treatment in the extension study. Aldurazyme is being developed by BioMarin Pharmaceutical and Genzyme General.
March 5, 2002
Phase III trial results suggest that Novartis' Elidel (pimecrolimus) cream 1% is more effective than a conventional treatment in reducing the incidence of disease flares. The 12-month, multicenter, double-blind study included 713 pediatric eczema subjects ages two to 17 years. The trial compared a long-term Elidel treatment regimen with a current conventional therapy regimen. Subjects applied either treatment at the earliest signs or symptoms of the disease. Both groups also used topical corticosteroids to treat any severe flares. At both six and 12 months, results showed that Elidel significantly reduced flare incidence compared to the conventional therapy. Additionally, 57% of subjects treated with Elidel had no flares that required corticosteroid treatment, compared to 32% in the control group.