July 24, 2017
Spark Therapeutics has published phase III clinical trial data of voretigene neparvovec for the treatment of patients with vision loss due to biallelic RPE65-mediated inherited retinal disease (IRD). In the randomized, controlled gene therapy trial, voretigene neparvovec improved functional vision, light sensitivity and visual field. Results showed a statistically significant and clinically meaningful difference between intervention (n=21) and control participants (n=10) at one year, per the clinical trial’s primary endpoint, mean bilateral multi-luminance mobility testing (MLMT) change score (difference of 1.6; 95% CI, 0.72, 2.41; p=0.0013). Participants maintained functional gains observed 30 days post-administration at the one-year primary endpoint. MLMT evaluates functional vision by documenting the participants’ ability to navigate a mobility course under a variety of specified light levels ranging from one lux (equivalent to, for example, a moonless summer night) to 400 lux (equivalent to, for example, an office environment). In May 2017, Spark Therapeutics completed the rolling submission of a BLA with the FDA.
November 28, 2016
Ocular Therapeutix reported results of a phase III trial of Dextenza (dexamethasone insert) 0.4mg for the treatment of post-surgical ocular inflammation and pain. This prospective, multicenter, 1:1 randomized, parallel-arm, double-masked, vehicle-controlled study enrolled 438 patients who were undergoing clear corneal cataract surgery at 21 sites throughout the U.S. The trial successfully met its two primary efficacy endpoints for inflammation and pain, achieving statistically significant differences between the treatment group and the placebo group for the absence of inflammatory cells on day 14 and the absence of pain on day eight, respectively. Fifty-two point three percent of patients treated with Dextenza showed an absence of inflammatory cells in the anterior chamber of the study eye on day 14, compared to 31.1% of those receiving the placebo vehicle control punctum plug (p<0.0001). Seventy-nine point six percent of patients treated with Dextenza reported absence of pain in the study eye on day eight, compared to 61.3% of those receiving the placebo vehicle control punctum plug (p<0.0001). Ocular Therapeutix has submitted an NDA to the FDA.
May 30, 2016
Encore Vision released results of a phase I-II study of EV06 ophthalmic solution 1.5% for the treatment of presbyopia. The randomized, double-masked, multicenter study examined the safety and efficacy of EV06 compared to placebo. A total of 75 subjects between the ages of 45 and 55 with distance corrected near visual acuity (DCNVA) worse than 20/40 and best corrected distance visual acuity (BCDVA) of 20/20 or better in each eye were randomized 2:1 to receive one drop of EV06 (n=50) or placebo (n=25) twice daily over 90 days. The mean change in DCNVA and BCDVA was evaluated throughout the study. The study met both primary safety and efficacy outcomes. A significant improvement of DCNVA from baseline was observed in the EV06 group compared to placebo, with onset of DCNVA improvement beginning at day 15 (p=0.017) and continuing throughout the 90-day study period (p=0.005). EV06 outperformed placebo in objective and subjective measures throughout the study duration. EV06 was well-tolerated. Encore intends future clinical studies of EV06.
RegeneRx Biopharmaceuticals issued results of a phase II/III trial of RGN-259 for the treatment of dry eye. The 317-patient trial demonstrated statistically significant improvements in both signs and symptoms of dry eye with 0.05% and 0.1% RGN-259 compared to placebo in a dose dependent manner during a 28-day dosing period. While the primary outcome measures were not met, several key related pre-specified endpoints and subgroups of patients with more severe dry eye showed statistically significant treatment effects. On the final day of dosing (day 28), patients receiving 0.1% RGN-259 had a statistically significant reduction in ocular discomfort during Controlled Adverse Environment (CAE) Model exposure when compared to placebo (Intent-to-Treat Population (ITT), p=0.043). Importantly, this result was also observed in the previous phase II trial in patients treated with 0.1% RGN-259 (ITT, p=0.024), thereby demonstrating a symptom endpoint in two independent trials. A statistically significant ocular discomfort improvement after CAE exposure on day 28 was also observed in the 0.05% and 0.1% RGN-259 treatment arms when compared to placebo (ITT, p=0.0366 and p=0.0072, respectively) indicating a dose dependent response. Efficacy in an environmental setting was also demonstrated in more symptomatic patients at baseline, with statistically significant improvements in ocular discomfort observed at day 28 prior to CAE in patients receiving 0.05% and 0.1% RGN-259 compared to placebo (p=0.022 and p=0.006, respectively). The company plans to conduct a confirmatory phase III study to start by the fourth quarter of 2016.
May 23, 2016
Envisia Therapeutics reported an interim three-month analysis of an ongoing safety and efficacy evaluation of the low dosage form of ENV515 XR (travoprost) for sustained reduction in intraocular pressure (IOP). The second cohort of the ongoing phase II trial was a 12-month safety and efficacy evaluation of the low dosage form of ENV515 that was designed as an open-label trial that enrolled five glaucoma patients at sites within the U.S. The low dosage form of ENV515, administered once on day one, achieved the interim efficacy endpoint in this three-month analysis, time-matched 8 a.m. IOP over the three-month post-dose period, with -7.1mmHg or -27% change from IOP baseline that was comparable to topical timolol 0.5% twice daily with -7.4mmHg or -28% change from IOP baseline, administered to the non-study eye. ENV515 was well-tolerated and there were no serious adverse events, no changes in corneal endothelial cell counts evaluated by an independent reading center and no changes in corneal thickness. The most common adverse event was early-onset transient hyperemia, or eye redness, related to the dosing procedure.
November 16, 2015
Shire has released results of a phase
III study of lifitegrast for dry eye disease.
OPUS-3 compared lifitegrast to placebo
administered twice daily for 84 days (12
weeks) in patients with dry eye, a recent
history of artificial tear use within 30 days
of study entry and an eye dryness score
(EDS)=40. Lifitegrast met the single primary
endpoint for patient-reported symptoms of
eye dryness (mean change in Eye Dryness
Score from baseline to week 12) (treatment
difference of 7.16 [95% CI], 3.04, 11.28;
p=0.0007). In OPUS-3, lifitegrast met the secondary
endpoints of symptom improvement
at days 14 and 42 (treatment difference (95%
CI) 7.85(4.33, 11.37) and 9.32 (5.44, 13.20)
respectively, (p<0.0001)). OPUS-3 topline
results replicated the co-primary symptom
endpoint of OPUS-2, a phase III efficacy and
safety study (p<0.0001). OPUS-2 did not
meet the co-primary endpoint for the sign
of inferior corneal staining score, (p=0.6186).
Shire plans to use those data as part of the
resubmission of the NDA for lifitegrast for the
treatment of signs and symptoms for dry eye
disease in the first quarter of 2016.
August 3, 2015
Allegro Ophthalmics reported results of
a phase II trial of Luminate (ALG-1001) in
patients with vitreomacular traction (VMT) or
vitreomacular adhesion (VMA). The prospective,
randomized, double-masked, placebo-controlled
trial evaluated Luminate in 106
study subjects. Sixty-five percent of eyes
treated with the 3.2mg dose of Luminate
achieved release of VMT or VMA by day 90
(end-of-study), compared to 9.7% of those
in the placebo control group (p=0.0129). The
study, which included three Luminate groups
(2mg, 2.5mg or 3.2mg) and a balanced salt
solution (BSS) placebo group, also found that
Luminate was well tolerated, with no drug
toxicity or intraocular inflammation noted
with repeated intravitreal injections. Currently
in phase II clinical trials for multiple indications,
including diabetic macular edema and
non-proliferative diabetic retinopathy, Luminate
is an investigational drug not approved
by the FDA for commercial sale in the U.S.
June 29, 2015
Avalanche Biotechnologies reported results
of a phase IIa study of AVA-101 for wet age-related
macular degeneration (wet AMD). The
study enrolled 32 subjects aged 55 or older with
wet AMD and randomized them to an
AVA-101 treatment group (n=21) or a control
group (n=11). Subjects in both groups received
two ranibizumab injections at day zero and
week four, and ranibizumab rescue therapy
was allowed according to pre-specified criteria
beginning at week eight. In the study, best
corrected visual acuity (BCVA) mean change
from baseline showed a difference of 11.5 letters
between the treatment (+2.2 letters) and control
(-9.3 letters) groups (95% CI, 2.3-20.7 letters).
Additionally, a significant number of AVA-101
treated subjects (42.9%) improved or maintained
stable vision with two or fewer rescue
injections compared with subjects in the control
group (9.1%). Importantly, BCVA improvement
of at least 10 letters with two or fewer rescue
injections was observed in 23.8% of treated
subjects and 0% of subjects in the control group.
No serious adverse events related to AVA-101
were observed. These data will help inform the
design of Avalanche’s phase IIb AVA-101 study,
which the company plans to conduct at multiple
centers in the U.S. later this year.
May 18, 2015
Aerie Pharmaceuticals reported results of
a phase III study of Rhopressa for its ability to
lower intraocular pressure (IOP) in patients with
glaucoma or ocular hypertension. Rhopressa
did not meet its primary efficacy endpoint of
demonstrating non-inferiority of IOP lowering
for Rhopressa compared to twice-daily
timolol, based upon IOP measurements at the
end of week two, week six and day 90. The
Rocket 1 study included 182 patients in the
Rhopressa once-daily arm and 188 patients
in the timolol twice-daily arm. The baseline
IOPs tested in the study ranged from above
20 to below 27mmHg. The results showed a
slight loss of efficacy in the week six and day
90 measurements. Across the Rhopressa study
of 182 patients, 36 patients or approximately
20% showed signs of loss of efficacy during the
study. The primary adverse event was hyperemia,
which was experienced by approximately
35% of the Rhopressa patients, of which 80%
was reported as mild. Rhopressa demonstrated
non-inferiority compared to timolol for patients
in the study with IOPs below 26mmHg at all
nine measured time points and numerical
superiority over timolol at the majority of
measured time points. The Baltimore Eye
Survey points to approximately 80% of newly
diagnosed glaucoma patients having IOPs of
26mmHg or less. Pending successful results
from the remaining phase III registration trials
and a potential additional phase III registration
trial for Rhopressa, the company expects to
submit an NDA filing by the end of 2016.
May 11, 2015
AbbVie released results of a phase III trial
of Humira (adalimumab) for adults with
active, non-infectious, intermediate, posterior
or panuveitis who still experience intraocular
inflammation while on systemic corticosteroid
therapy. The double-masked, randomized,
placebo-controlled study enrolled 217 adult
patients—110 were treated with Humira
and 107 received placebo. The Humira group
received an 80mg baseline loading dose
followed by 40mg given by subcutaneous
injection every other week for up to 80 weeks.
At study entry, all subjects received a 60mg
prednisone burst followed by a complete taper
over 15 weeks. Starting at week six and every
visit thereafter, all patients were assessed for
treatment failure (TF). The study found that
compared to placebo, patients on Humira
were less likely to experience TF (hazard ratio=
0.5; 95% CI, 0.360.70; P<0.001). Median
time to TF was prolonged by 87%, from three
months for placebo to 5.6 months for Humira.
The rates of adverse events (AEs) were 1,047
events per 100 patient years (PY) for Humira-treated
patients v. 965 events per 100PY for
placebo patients; rates of serious AEs were 29
events per 100PY for Humira-treated patients
v. 13 events per 100PY for placebo patients. In
May 2014, AbbVie received Orphan Drug designation
from the FDA for the investigational
treatment of certain forms of noninfectious
uveitis with Humira. U.S. and E.U. regulatory
submissions are expected this year.
April 13, 2015
RegeneRx Biopharmaceuticals reported
results of a physician-initiated, phase II,
randomized, placebo controlled study of
RGN-259 in patients with severe dry eye. At
day 56, the RGN-259-treated group had 35.1%
reduction of ocular discomfort compared with
vehicle control (P=0.0141), and 59.1% reduction
of total corneal fluorescein staining compared
with vehicle control (P = 0.0108). Other
improvements seen in the RGN-259-treated
patients included tear film breakup time and
increased tear volume production. RGN-259
has been designated an orphan drug for the
treatment of neurotrophic keratopathy (NK).
RegeneRx recently was allowed by the FDA to
move into phase III clinical trials with RGN-259
for the treatment of patients with NK. The drug
candidate also is being studied in patients with
dry eye syndrome in the U.S. and Asia.
March 23, 2015
Ocular Therapeutix reported results
of a phase III study of OTX-DP (Sustained
Release Dexamethasone) for ocular inflammation
and pain following cataract surgery.
The multicenter, randomized, parallel-arm,
double-masked, vehicle-controlled study
enrolled 247 patients randomized 2:1 to
receive either OTX-DP or a placebo vehicle
control punctum plug without active drug.
33.7% of OTX-DP-treated patients showed
an absence of inflammatory cells in the
anterior chamber of the study eye on day 14
following drug product insertion, compared
to 14.6% of those receiving placebo
vehicle control punctum plug (p=0.0015).
In addition, 76.1% of patients receiving
OTX-DP reported absence of pain in the
study eye on day 8 following insertion of the
drug product, compared to 36.1% of those
receiving placebo vehicle control punctum
plug (p<0.0001). Ocular is continuing to
analyze the safety findings from the clinical
trial. The company is on track to submit an
NDA to the FDA for OTX-DP for post-surgical
ocular inflammation and pain in the second
quarter of 2015.
October 15, 2012
Alexion Pharmaceuticals released results from a phase II trial of eculizumab for the treatment of neuromyelitis optica (NMO). This 12-month, single-arm, open-label, investigator-initiated study enrolled 14 patients with severe, relapsing NMO who had experienced two or more disease relapses in the preceding six months or three such attacks in the preceding year. Subjects received eculizumab 600mg weekly for the first four weeks, followed by 900mg at week five and 900mg biweekly thereafter. The study achieved its primary endpoint with statistical significance: a decline in the median annualized attack rate from three attacks per patient pre-eculizumab treatment to zero attacks per patient during 12 months of chronic eculizumab treatment (p<0.0001). After 12 months, 86% (12 of 14) of these severely affected patients were completely attack-free. The median expanded disability status scale (EDSS) score improved from 4.3 pre-treatment to 3.5 after 12 months of eculizumab (p<0.01). All patients experienced either improvement or stability in all key outcome measures, including EDSS, ambulatory function and visual function. Eculizumab was well tolerated. The most frequent adverse events were headache, nausea and dizziness. Alexion expects to participate in a series of discussions with researchers and regulators to design a company-sponsored clinical study to further evaluate potential.
August 27, 2012
Lexicon Pharmaceuticals reported preliminary results from a phase I trial of LX7101 eyedrops for the treatment of glaucoma. This randomized, multi-arm study enrolled 63 patients. Subjects received 0.125% solution or 0.25% solution, or vehicle once daily for one week, followed by twice daily for a second week. Mean IOP changes from baseline at Day 14 for each LX7101 dose arm compared to vehicle at eight hours post-dose were 3.18mmHg for 0.125% (p=0.007) and 2.32mmHg for 0.25% (p=0.028), compared to 0.40mmHg for vehicle. Reductions from baseline at Day 14 in the diurnal mean IOP, representing mean changes across all daily time points, were 3.37mmHg for 0.125% and 3.52mmHg for 0.25%, compared to 2.17mmHg for vehicle. The drug was well tolerated at all doses, with no serious adverse events. Lexicon did not note its plans for LX7101.
Novartis published results from two phase III trials of ocriplasmin for the treatment of vitreomacular adhesion (VMA). These two multi-center, randomized, double-blind, placebo-controlled studies, Study 006 and Study 007, enrolled 652 patients. Subjects received a single intravitreal injection of ocriplasmin 125mcg, or placebo. After 28 days, following a single administration of ocriplasmin, resolution of vitreomacular adhesion was observed in 26.5% of patients compared to 10.1% in the placebo group (p<0.001). This statistically significant difference was maintained through six months of observation. By the end of the six-month observation period, fewer patients required a vitrectomy in the ocriplasmin treated group, compared to placebo (17.7% vs. 26.6% respectively, p=0.02). The drug was well tolerated. The most frequent adverse event was vitreous floaters. Ocriplasmin is currently under review with the EMA and gained a positive recommendation in July from the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee.
June 25, 2012
RegeneRx Biopharmaceuticals issued results from a phase II trial of RGN-259 for the treatment of severe dry eye. This double-masked, vehicle-controlled, physician-sponsored study enrolled nine patients. Subjects received RGN-259 or vehicle control six times daily for 28 days. Statistically significant differences in sign and symptom assessments, such as ocular discomfort and corneal fluorescein staining, were seen throughout the study. Twenty-eight days post-treatment showed the RGN-259-treated group had a 35.1% reduction of ocular discomfort compared to vehicle control (p=0.0141), and a 59.1% reduction of total corneal fluorescein staining compared to vehicle control (p=0.0108). Tear film breakup time and increased tear volume production were also seen at the 28-day post-treatment checkups. RGN-259 was well tolerated. RegeneRx researchers are conducting additional analysis of the patient groups and will be submitting a manuscript for publication later this year.
July 4, 2011
Mimetogen released results from a phase II trial of MIM-D3 for the treatment of dry eye. This randomized, double-blind, placebo-controlled study enrolled 150 subjects who received a low dose (1%) or high dose (5%) of MIM-D3 or placebo twice/day for 28 days. Statistically significant improvements in signs and symptoms were seen with both doses of MIM-D3 compared to placebo. Data also showed good safety and tolerability profiles.
March 28, 2011
InSite Vision released results from a phase I/II trial of ISV-303 for the reduction of pain and inflammation associated with ocular surgery. The randomized, placebo-controlled study enrolled 160 subjects who were placed in one of four study arms: ISV-303 administered once-daily or twice-daily, Xibrom (standard of care) administered twice-daily, or placebo. The drug therapy was administered for two weeks following an ocular surgery procedure. The primary endpoint was the absence of cells in the anterior chamber of the eye at day 15 post surgery. Once-daily ISV-303 achieved statistically significant superiority compared to placebo (53.3% versus 19%; p≡0.0016) for the primary endpoint. Secondary endpoints, including reduction of flare, pain and discomfort, also achieved statistical significance compared with placebo. While once-daily ISV-303 achieved a numerically superior difference in the primary endpoint versus twice-daily Xibrom (53.3% versus 42.2%), the results did not reach statistical significance. ISV-303 was well tolerated.
September 6, 2010
ThromboGenics issued positive results from a phase III trial evaluating microplasmin for the non-surgical treatment of vitreomacular adhesion (VMA). This randomized, placebo controlled, double blind trial (TG-MV-007) enrolled 326 subjects with focal VMA who received a 125ug microplasmin intravitreal injection or placebo injection. The primary endpoint was the proportion of subjects with non-surgical resolution of focal vitreomacular adhesion at day 28. Of the subjects who received microplasmin, 25.3% achieved resolution of their VMA at 28 days, compared to 6.2% of the placebo group (p≡0.001). In subjects without epiretinal membrane, microplasmin was shown to be even more effective, with 34.5% seeing resolution at 28 days, compared to 6.4% of the placebo group. Additional endpoints were also reached. Microplasmin was also highly effective in treating full thickness macular hole and improving visual acuity, both without the need for vitrectomy. Microplasmin was generally safe and well tolerated.
August 31, 2009
Resolvyx issued positive results from a phase II study of RX-10045 for the treatment of chronic dry eye syndrome. This 28-day, randomized, multi-center, placebo-controlled study enrolled 232 subjects with moderate dry eye who received one of three doses of RX-10045 administered topically twice daily. A controlled adverse environment (CAE) was utilized to measure corneal staining in a stressful drying environment and daily patient diaries were maintained using a standard visual analog scale to assess symptom improvement over the course of the study. RX-10045 produced a 75% reduction from baseline in CAE-induced staining of the central cornea (p< 0.00001); this improvement approached statistical significance over placebo (p≡0.11). RX-10045 also led to a significant improvement in CAE-induced staining in the inferior cornea and in the composite of central and inferior cornea, which also approached statistical significance over placebo (p≡0.09). In addition, a significant dose-dependent improvement from baseline in symptoms recorded in daily patient diaries was observed. RX-10045 was superior to placebo on the primary symptomatic endpoint of Worst Symptom Score (p<0.02), as well as on several individual symptoms. The onset of symptom relief occurred within the first week of treatment, and symptoms continued to improve over the course of the 28-day study.
January 26, 2009
Ista reported positive results from a phase IIb trial of ecabet sodium for the treatment of dry eye disease. This randomized trial enrolled144 subjects who received either ecabet sodium or placebo four times per day for 43 days, under normal environmental conditions. The object of the study was to investigate ecabet sodium's effects on the signs of tear production (Anesthetized and Unanesthetized Schirmer Tests), tear film quality (TFBUT) and subjective symptoms. Treatment with ecabet sodium led to a strong positive trend in TFBUT and a positive trend in the quantity of tears produced (Schirmer Test). The increased Schirmer Test score was seen as early as day 22 of treatment and continued to trend upwards through day 43. In contrast, there were no trends seen in the placebo group for either objective sign. In addition, there were no trends seen in either group in subjective symptoms as measured by the Ocular Surface Disease Index (OSDI) or patient's worst reported symptom. Adverse events were uncommon and similar between the treatment and placebo groups. Based on the results, Ista plans to move development into phase III studies.
October 20, 2008
Sirion reported preliminary results from a clinical trial of Durezol for the treatment of anterior uveitis. This multicenter, randomized, double-masked trial enrolled 90 subjects with endogenous anterior uveitis. The subjects received Durezol 0.05% dosed four times daily (QID) or Pred Forte 1%, dosed eight times daily, both for 14 days, with two weeks of tapering at half the dose and two weeks of follow-up. The primary endpoint was the difference from baseline in anterior chamber cell grades between the Durezol and Pred Forte groups. At Day 14, the Durezol group achieved a mean cell grade reduction of 2.1, compared to 1.9 in the Pred Forte group, confirming the non-inferiority of Durezol to Pred Forte. In addition, 69% of subjects receiving Durezol had an AC cell grade of 0 (less than or equal to 1 cell) at Day 14 compared to 62% of subjects receiving Pred Forte; this trend continued through Day 42. Durezol also demonstrated an advantage in pain reduction from baseline over Pred Forte. At Day 7 the Durezol group had a reduction in mean pain score of 71% versus 64% in the Pred Forte group. Furthermore, Durezol led to a mean reduction in total symptom score at Day 14 of 76% versus 71% for Pred Forte. This difference was maintained through Day 42 with the Durezol group reducing the total symptom score by 86% versus 76% for the Pred Forte group. Treatment was well tolerated. Based on the results, Sirion plans to file a sNDA with the FDA for anterior uveitis.
July 21, 2008
ThromboGenics issued positive results from a phase IIb trial of microplasmin in vitrectomy procedures. This randomized, double-masked, placebo-controlled, dose-ranging trial, dubbed MIVI III (Microplasmin for Vitreous Injection III), enrolled 125 subjects scheduled for vitrectomy, in the US. The subjects received three doses of microplasmin intravitreal injection (25, 75 and 125 µg) or placebo given 7 days prior to the planned vitrectomy. Results showed a clear dose response curve, with the highest dose of microplasmin (125 ug) delivering the best results. In this arm, 10 of the 32 subjects receiving this dose had resolution of their underlying disease and therefore did not need a vitrectomy, compared to 1 out of 31 subjects in the placebo arm. The visual acuity of all of the subjects was also measured at day 35 after the injection of microplasmin or placebo, whether or not they had a vitrectomy. The subjects who received the highest dose of microplasmin showed an improvement in vision (6.9 more letters read on a standard eye chart compared to a baseline reading prior to treatment); compared with a 4.7 letter improvement for all microplasmin treated subjects and a 0.1 letter improvement for the placebo group. Microplasmin was well tolerated. Based on the results ThrmboGenics plans to begin phase III trials in late 2008 or early 2009.
May 26, 2008
Allergy Therapeutics released positive results from a phase III trial of Pollinex Quattro for the treatment of seasonal allergic rhino-conjunctivitis caused by grass allergy. This double-blind placebo-controlled study, dubbed G301, enrolled 1,028 subjects in the United States, Canada and Europe. The subjects received four injections of either Pollinex Quattro or placebo treatment over three weeks prior to the 2007 grass pollen season. They then recorded rhino-conjunctivitis symptoms and medication intake over the course of the pollen season from May to September. The primary endpoint was the difference in combined symptom plus medication score between active and placebo treatment over the four peak pollen weeks of the season. The primary endpoint was reached, with a 13.3% improvement in the Pollinex Quattro group over placebo (p = 0.0038) in the Intent To Treat population and a 26.9% improvement over placebo in the prospectively defined patient population (p = 0.0031). Treatment was determined to be safe and well tolerated. Based on the results Allergy Therapeutics plans to file an MAA in the EU in quarter one of 2009.
May 5, 2008
ISTA issued positive preliminary results from a phase III trial of Bepreve for the treatment of allergic conjunctivitis. This multi-center, double-masked, placebo-controlled study enrolled 130 subjects, 117 of whom completed the study. The subjects received two concentrations of Bepreve in two dosing schedules, once-daily and twice-daily. They were evaluated on three separate occasions for response at eight hours and sixteen hours. Both concentrations demonstrated statistically significant reductions in the primary study endpoint of ocular itching. In addition, both concentrations produced statistically significant effects on the rapid response rate and in the secondary endpoints measuring additional signs and symptoms of ocular allergy, as well as improvement in total nasal symptoms. The strongest clinical effect was achieved with twice-daily dosing of either concentration. There were no serious ocular adverse events reported. Based on positive phase III results ISTA plans to file an NDA with the FDA during the second half of 2008.
Targeted Genetics reported positive results from a phase I/II trial of their RPE65 gene therapy for the treatment of retinal dystrophy due to Leber's congenital amaurosis (LCA). This single-center, open label study enrolled nine young adults, between the ages of 17 and 23 years, with early-onset severe retinal dystrophy due to LCA. The subjects were administered a single subretinal injection of the AAV vector expressing RPE65. In each subject, the eye with the worse acuity was selected as the study eye and the other was used as a control. After two weeks, data from the first three treated subjects showed that they had improved vision in the injected eye and could read several lines on an eye chart. They also had less nystagmus after six months and one subject showed a significant consistent improvement in visual function and subjective tests of visual mobility No adverse events or inflammation were reported. Based on the results the company planned to enroll additional subjects into the trial.
December 10, 2007
Thrombogenics released positive results from a phase IIa trial of microplasmin for the treatment of vitreomacular traction, including macular holes. This sham injection controlled, dose ascending study, dubbed MIVI IIT, enrolled thirty subjects in Europe. Subjects received placebo, 75 micrograms or 125 micrograms of treatment. Microplasmin was safe and well tolerated. Posterior vitreous detachment (PVD) was induced, leading to some cases of the non-surgical resolution of traction and/or holes, with improvement in vision, preventing the need for vitrectomy. Nine of the twenty four microplasmin treated subjects had resolution of their vitreomacular traction (including macular hole closure in two of the four subjects) without the need for vitrectomy. None of the six sham injected subjects had resolution of their vitreomacular traction (including two with macular hole). Based on the results, Thrombogenics plans to enroll an additional fifteen subjects to evaluate a higher 175 microgram dose of microplasmin.
November 5, 2007
Sirion reported positive results from two phase III trials of difluprednate for the treatment of inflammation following ocular surgery. These multi-center, randomized, double- masked studies enrolled 439 subjects who received difluprednate (0.05%) or placebo, dosed two (BID) or four (QID) times daily beginning twenty-four hours after surgery. The primary efficacy endpoint was the proportion of subjects whose inflammation reached Grade 0 at Day eight. Both difluprednate dosing regimens reached statistical significance over placebo at Day eight and maintaining superiority through both the treatment period (Day fifteen) and the tapering period (Day twenty-nine). At Day fifteen, 56% of subjects on the BID regimen reached Grade 0 compared to 16% in the placebo group (p<0.0001). Statistical significance was also reached in the QID regimen, with 63% of the subjects achieving a Grade 0 at Day fifteen. In addition, both difluprednate groups were statistically better than placebo in eliminating pain as measured using the Visual Analogue Scale. Treatment was well tolerated, with few drug related adverse events. Mean intraocular pressure for all study groups remained within the normal range throughout the trial. Based on the results, Sirion plans to move forward with NDA filing.
October 15, 2007
Alacrity reported positive results from a phase II trial of ALTY-0501 for the treatment of Dry Eye Syndrome. This double-masked, randomized, parallel-group study enrolled 160 subjects. The subjects were exposed to a controlled adverse environment (CAE) on day 1 and asked to self-administer either ALTY-0501 eye drops or placebo eye drops four times per day. They were subsequently exposed to the controlled adverse environment on days 28 and 56. The subjects who received ALTY-0501 had significantly lower scores for fluorescein staining of the total cornea-a measure of damage to the ocular surface than those receiving placebo on day 28 (p < 0.05). Statistically significant differences from placebo were also observed with total corneal and conjunctival staining (p < 0.05), superior corneal staining (p < 0.001) and nasal conjunctival staining (p < 0.05). In addition, ALTY-0501 led to significantly better scores in patient recorded diaries measuring the severity of dry eye symptoms over 56 days when compared to placebo. Statistically significant lower scores were seen for the symptoms of burning (p < 0.0001), stinging (p < 0.0001), and grittiness (p < 0.0001). Based on the results, phase IIb/III trials are planned for late 2007 to early 2008.
October 30, 2006
Thrombogenics issued positive results from a phase IIa trial of microplasmin for the treatment of vitreoretinal disorders during vitrectomy. The trial was designed to evaluate the effect of microplasmin as a surgical adjunct to vitrectomy for induction of PVD (posterior vitreous detachment). This open-label, dose-ranging trial enrolled 60 subjects undergoing vitrectomy who received an intraocular injection of microplasmin in one of six regimens: cohort 1-25 micrograms 1hr prior to vitrectomy, cohort 2 – 25 micrograms 24hrs prior to vitrectomy, cohort 3 – 25 micrograms 7 days prior to vitrectomy, cohort 4 – 50 micrograms 24 hrs prior to vitrectomy, cohort 5 – 75 micrograms 24 hrs prior to vitrectomy and cohort 6 – 125 micrograms 24 hrs prior to vitrectomy. Treatment was well tolerated at all dose levels. Efficacy results revealed that the subjects in cohorts 2-6 were able to have PVD induced with relatively low amounts of suction and without the need for mechanical intervention. The most effective treatment regimen was in cohort 3, in which 5 out of 10 subjects had a total PVD before vitrectomy without suction or mechanical intervention. Based on these results Thrombogenics plans to initiate a phase IIb trial before the end of 2006.
March 20, 2006
Neurotech reported positive results of a phase I trial of NT-501, for the treatment of retinitis pigmentosa (RP), in the Proceedings of the National Academy of Sciences. Trial data indicated that NT-501 intra-ocular implants were safe and generally well tolerated. Preliminary efficacy data were also positive, with 3 of the 7 subjects evaluable for visual acuity experiencing improvements in this measure (the trial was not powered to investigate clinical efficacy). This open-label study enrolled 10 subjects at the National Eye Institute, who received NT-501 implants at one of two dose levels for 6 months. Based on these results, the company announced plans to initiate a pair of phase II trials of the drug for the treatment of RP later in 2006.
February 27, 2006
ISTA Pharmaceuticals has reported positive results of a phase IIb trial of ecabet sodium, for the treatment of keratoconjunctivitis sicca (KCS, also know as dry eye syndrome). Preliminary study data yielded a positive trend in reducing corneal staining and rapid blinking (two primary symptoms of the condition), at the lower trial dose. Additional trends were noted in reducing symptom severity as measured by ocular surface disease index and most bothersome symptom reports. No efficacy trends were established for the higher trial dose; additional analyses of the data were ongoing. This randomized, placebo-controlled study enrolled 162 patients, who received one of two dose concentrations of the drug (3.0% or 3.9%) or placebo four-times daily for 90 days.
January 9, 2006
Nascent Pharmaceuticals reported positive results of a phase IIb trial of iDESTRIN (NP50301), for the treatment of dry-eye syndrome. Among subjects with moderate to severe disease, the highest dose of the drug produced a significant improvement in the study's primary endpoint, symptoms severity score on the Schirmer's Test, at 8 weeks (p=0.027) and 12 weeks (p=0.004) in both eyes, vs. vehicle control. Significant improvements were also noted in this group for secondary endpoints: superficial punctuate keratopathy (p=0.020) and corneal staining (p=0.045) improved at 12 weeks; and subjective foreign body sensation improved as early as 4 weeks (p<0.04) and was maintained through the end of the study. This randomized, vehicle-controlled, double-blind study enrolled 90 patients, who received one of 2 doses of the drug or placebo for 14 weeks.
December 5, 2005
InSite Vision has issued positive result of a phase III trial of AzaSite (DuraSite azithromycin), their investigational anti- infective eye drops for the treatment of bacterial conjunctivitis. Trial data met their primary efficacy endpoint, producing statistical non-inferiority in clinical resolution rate relative to approved treatment with tobramycin (80% vs. 78%, respectively) over fewer total doses. Adverse events occurred at similar rates between treatment groups. This randomized, double-blind, active-controlled study enrolled 316 conjunctivitis-confirmed patients across 47 sites in the US (n=41) and Latin America (n=6). Subjects were randomized to receive either a regimen of AzaSite (twice daily for 2 days, then once daily for 3 days), or an ophthalmic formulation of tobramycin (four times daily for 5 days).
May 9, 2005
Genaera issued interim results of a phase II trial, dubbed MSI-1256F-208, of Evizon (squalamine lactate) for the treatment of wet age-related macular degeneration (AMD). 9-week data from the ongoing study yielded evidence of efficacy, with Evizon producing a mean gain from baseline of 1.3 EDTRS letters (range +16 to -17; n=24) in visual acuity, vs. a loss of 0.9 EDTRS letters (range +15 to -19; n= 15) for placebo. This ongoing, randomized, double- blind, placebo-controlled, multi-center study has enrolled 46 subjects across 15 US sites, who continue to receive monthly infusions of Evizon or placebo, in combination with photodynamic therapy with vertepofin (PDT) at week 3, with optional additional PDT at weeks 15 and 27 based on need. The treatment period is scheduled to last through week 25, with a 1 year observational follow-up scheduled thereafter.
Neurotech SA issued positive results of a phase I trial, dubbed 03-EI-0234, of NT-501, their investigational ciliary neurotrophic factor (CNTF) delivery vector based on their Encapsulated Cell Technology platform, for the treatment of retinitis pigmentosa (RP). Primary safety endpoints were achieved, with no reported serious adverse events and a positive overall tolerability profile. Preliminary efficacy was also noted, with some patients experiencing a one-line-or-greater improvement in visual acuity. This open-label study enrolled 10 patients with late stage RP, who received intravitreal implantation of NT-501 ECT cells at one of two dose levels (5-fold difference between doses). The company announced plans to initiate a multi- center phase II trial of the drug in the near future, based on these results.
Regeneron reported positive results of a phase I trial of systemically-administered Vascular Endothelial Growth Factor (VEGF) Trap, for the treatment of wet age-related macular degeneration (AMD). Preliminary trial data indicated that the drug produced a significant decrease in excess retinal thickness, vs. placebo. This effect was seen to be dose dependent in both magnitude and duration. The drug also produced a dose-dependent increase in blood pressure, a commonly observed effect of systemically administered anti-VEGF agents. This randomized, double-blind, placebo-controlled, ascending dose study enrolled 25 subjects, who received one of three doses of systemic VEGF Trap (0.3 mg/kg, 1.0 mg/kg or 3.0 mg/kg) or placebo. Based on these results, the company announced plans to initiate a phase I trial in mid-2005 to investigate intravitreal injections of VEGF Trap, in hopes of limiting systemic hypertension.
Sirna Therapeutics reported positive results of a phase I trial of Sirna-027, their short interfering RNA (siRNA) treatment for the treatment of wet AMD. Interim results from the study met primary safety and tolerability endpoints, with no drug-related systemic or local adverse events noted. Dose-limiting toxicity/ maximum tolerated dose had not yet been reached. Preliminary evidence of efficacy, including stabilization of visual acuity in all patients for the duration of treatment, was observed. This open- label dose-escalation study had enrolled and treated 14 of 30 planned subjects across 4 US sites to date, with single intravitreal doses ranging from 100-800 mcg. The company announced plans to initiate phase II trials, pending final positive analysis of the data set.
February 14, 2005
Inspire Pharmaceuticals issued results of a phase III trial of diquafosol tetrasodium, their investigational treatment for dry eye. Study results indicated that the drug did not to meet its primary endpoint, failing to establish a statistically significant improvement in corneal clearing after 6 weeks of therapy, vs. placebo (p=0.369). The drug did achieve significance in a number of secondary endpoints (p<0.05), including mean corneal staining, mean conjunctival staining and conjunctival clearing, but failed to achieve significant improvement in symptom assessment scores from either the Ocular Surface Disease Index or analysis of patients' worst symptom score. The drug did demonstrate a higher incidence of the most common adverse event, burning/stinging on instillation, but prevalence was still <5%, vs. placebo. This randomized, double-blind, placebo-controlled study enrolled 640 patients across 34 sites in the US; patients received treatment with either a 2% diquafosol ophthalmic solution or placebo for 6 weeks. Based on these data, Inspire announced that they had submitted an amendment to their NDA currently under review.
August 18, 2003
Inspire Pharmaceuticals reported positive results from a phase IIIb trial investigating diquafosol (INS365 Ophthalmic), a P2Y2 receptor agonist for the treatment of dry eye. The study included a environmental component and an experimental Controlled Adverse Environment (CAE) chamber designed to exacerbate dry eye. Results showed statistically significant improvements in ocular staining compared with placebo among subjects in the environmental group. No treatment-related serious adverse events were reported with the incidence of adverse events similar to placebo. Statistical significance was not achieved with respect to the primary endpoints of ocular staining and discomfort after exposure in the CAE chamber. The four-week, placebo-controlled, double blind study enrolled 222 subjects with dry eye and compared the safety and efficacy of 2% diquafosol tetrasodium ophthalmic eye drops to placebo.
May 19, 2003
Genaera reported positive early results from a phase I/II trial investigating squalamine, an anti-angiogenic drug for the treatment of age-related macular degeneration (AMD). Early results demonstrated shrinkage in the size of choroidal neovascularization lesions and stabilization of the lesions in some subjects. In addition, early trends for visual acuity showed some improvement in more than three lines of vision. The primary endpoint measures are visual acuity, ocular angiography and fundus photography. No serious adverse events or withdrawals from therapy have occurred in the trial to date. Squalamine is administered intravenously at doses of 25 or 50 mg/m2, once weekly for 4 weeks. The study is enrolling 40 subjects with AMD and is being conducted in Mexico City.
September 30, 2002
The results of a multi-site, randomized, double-blind phase II trial indicated ISV-401 elicited both clinical resolution and bacterial resolution of acute bacterial conjunctivitis. One drop of 1% ISV-401 with a DuraSite vehicle or placebo vehicle was administered in the infected eye(s) of 30 subjects twice on the first day and once in the morning on each of the following four days. The results showed that six drops of ISV-401 received over five consecutive days produced clinical results in treating both gram-positive and gram-negative strains of acute bacterial conjunctivitis comparable to results produced by more than 35 drops of currently marketed drugs. ISV-401 is a product of InSite Vision.
June 24, 2002
Positive results were reported from the second phase III trial of Inspire Pharmaceuticals' INS365 Ophthalmic for the treatment of dry eye disease. The 527-subject, six-month, double-masked trial evaluated INS365 Ophthalmic 1.0% and 2.0% eye drops versus placebo. Results showed that INS365 2.0% eye drops produced a highly statistically significant improvement compared to placebo in the primary objective endpoint (corneal staining). Statistically significant results were also obtained in secondary objective endpoints, including conjunctival staining. While statistical significance was not met in the primary subjective endpoint of the trial - clearing of the ocular symptom of foreign body sensation at six weeks - positive results were obtained. The number of subjects who cleared foreign body sensation was consistently higher with INS365 compared to placebo throughout the study period.
January 21, 2002
Preliminary phase III trial results indicate that INS365 Ophthalmic did not meet the primary efficacy objectives of the study. Subject improvement on INS365 Ophthalmic was similar to that observed in the phase II trial; however, an improvement of similar magnitude was observed in the placebo group. The trial was designed to compare INS365 Ophthalmic eye drops at concentrations of 1% and 2% to placebo for the treatment of dry eye. This was first of two phase III trials for INS365 Ophthalmic - the second trial is ongoing, and efficacy results are expected in the second quarter of 2002. Inspire Pharmaceuticals will decide whether or not to continue the program after the results from the second trial are available.