November 7, 2016
Aerie Pharmaceuticals reported results of a phase III trial of Rhopressa tested for its ability to lower intraocular pressure (IOP) in patients with glaucoma or ocular hypertension. Rocket 4 enrolled approximately 700 patients and was a two-arm, six-month trial, which included a 90-day efficacy readout. The range for the primary endpoint includes patients with baseline IOPs from above 20mmHg (millimeters of mercury) to below 25mmHg. Rhopressa dosed once-daily achieved its primary efficacy endpoint demonstrating non-inferiority compared to twice-daily timolol for patients with baseline IOPs ranging from above 20 to below 25mmHg. Rhopressa also demonstrated non-inferiority compared to timolol at the pre-specified secondary endpoint range of above 20 mmHg to below 27 mmHg, and also at a range of above 20mmHg to below 28mmHg. The Rocket 4 efficacy results for Rhopressa demonstrated a consistent level of IOP lowering across all baseline IOPs in the trial, and throughout the 90-day efficacy period. There were no drug-related systemic or serious adverse events. Aerie has withdrawn the Rhopressa NDA that was submitted to the FDA in the third quarter of 2016. The filing was withdrawn as the result of a third party manufacturing facility in Tampa, Florida, not being ready for pre-approval inspection by the FDA. The drug product contract manufacturer has advised Aerie and the FDA that it expects to be prepared for FDA inspection in January 2017, and Aerie expects to resubmit the Rhopressa NDA filing at that time.
February 29, 2016
Aerie Pharmaceuticals reported results of a second phase III trial of Rhopressa (netarsudil ophthalmic solution) 0.02%, a once-daily eye drop being tested for its ability to lower intraocular pressure (IOP) in patients with glaucoma or ocular hypertension. For the first 118 patients who reached the 12-month mark in Rocket 2, Rhopressa QD demonstrated a consistent level of IOP lowering at 8 am from day 90 through month 12, with a nominal variance of only 0.1 mmHg between day 90 and month 12. The first 118 patients on Rhopressa QD for the 12-month period demonstrated safety results consistent with those observed for the 90 day efficacy period. There were no new adverse events that developed over the 12-month period, and there were no drug-related serious adverse events. The most common adverse event was conjunctival hyperemia. Others included conjunctival hemorrhages, corneal deposits and blurry vision in 5% to 23% of the 118 patients. Increased hyperemia over baseline was observed by biomicroscopy at a rate of 30%, of which 76% was considered mild. Hyperemia was sporadic; 70% of patients with prior conjunctival hyperemia had no hyperemia at month 12. Rocket 2 will be supported by Rocket 1 for the NDA filing, expected to be submitted to the FDA in the third quarter of 2016. Rocket 3 is a 12-month safety-only study in Canada currently in progress but not needed for NDA filing. A fourth phase III trial, Rocket 4, commenced in late September 2015, and is designed to provide adequate six-month safety data to meet regulatory filing requirements in Europe. It is also not required for the NDA filing in the U.S.
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.
January 20, 2014
Aerie Pharmaceuticals has reported results
of a phase I trial of a pharmacokinetics (PK)
study of AR-13324 glaucoma eye drops.
AR-13324 eye drops were administered
once-daily to 18 healthy individuals over an
eight-day period to assess systemic exposure
to the drug. The PK results demonstrated
very low systemic exposure to the drug,
with blood levels at or below the limit of
detection of 0.1ng/mL at all time points. In
addition, there were no drug-related effects
on systemic safety parameters such as blood
pressure and heart rate. All study subjects
had intraocular pressure (IOP) in the normotensive
range of 12mmHg to 21mmHg,
with an average diurnal IOPs for the group
of approximately 16mmHg prior to dosing.
After eight days of dosing, once-daily administration
of AR-13324 reduced the average
diurnal IOP to approximately 11mmHg,
representing a decrease of approximately
5mmHg, or over 30%. The completion of
the PK study is a step in preparing for two
planned phase III registration studies of AR-
13324, which are expected to commence by
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.
March 19, 2012
Bausch and Lomb and NixOx reported results from a phase IIb trial of BOL-303259-X for open-angle glaucoma or ocular hypertension. This trial enrolled 413 subjects who received various concentrations of BOL-303259-X or Xalatan 0.005% ophthalmic solution once daily for 28 days. The primary efficacy endpoint was the reduction in mean diurnal intraocular pressure (IOP) at day 28. BOL- 303259-X consistently lowered IOP in a dose-dependent manner. Two of the four doses tested showed greater IOP reduction compared with Xalatan 0.005%, with the differences reaching more than 1mmHg (p<0.01). The most efficacious dose of BOL-303259-X also showed positive results on a number of secondary endpoints, including consistently better control of IOP over 24 hours on day 28 as well as a statistically significant greater percentage of responders versus Xalatan 0.005%. The responder rate was 68.7% for the most efficacious dose of BOL- 303259-X, compared to 47.5% for Xalatan 0.005% (p≡0.006). The safety of BOL-303259-X was comparable to Xalatan.
May 12, 2008
Pfizer and NicOx reported mixed results from a phase II trial of PF-03187207 for the treatment of primary open-angle glaucoma or ocular hypertension. This US based, randomized, double masked study enrolled 215 subjects with one of these two conditions in one or both eyes. The subjects received twenty-eight days of treatment with either morning or evening doses of Xalatan 0.005% or five different doses of PF-03187207, some of which were tested with both morning or evening dosing arms. Intraocular pressure (IOP) was measured at 8am, 10am, 1pm and 4pm, at baseline and on days 7, 14, 21 and 28. The primary endpoint compared the two treatments in terms of the change in mean IOP from baseline at day 28. On this primary endpoint, evening administration of the highest dose of PF-03187207 showed a 12% (approximately 1 mmHg) greater reduction in diurnal IOP than evening administration of Xalatan, however this difference did not reach statistical significance. Secondary endpoints were reached with statistical significance. These included IOP lowering from baseline at 4 pm as an average across all study visits; evening administration of PF-03187207 was statistically significantly better than evening dosing of Xalatan by 22%, approximately 1.4 mmHg (p<0.05). Additional secondary endpoints were the reductions in diurnal IOP from baseline on days 7, 14 and 21, as well as the reductions from baseline at 8 am, 10 am, 1 pm and 4 pm, as an average across all study visits. Morning administration of the highest PF-03187207 dose demonstrated a statistically significant advantage compared to morning dosing of Xalatan on a number of these secondary endpoints, with the difference in IOP lowering ranging from 25% to 35%, approximately 1 mmHg to 2 mmHg (p<0.05). Based on the results Pfizer has decided not to launch a global phase III program. A phase II trial is currently underway in Japan; pending positive results Pfizer and NicOx may pursue potential registration in Asia.
March 17, 2008
Alcon issued positive results from a phase II trial of anecortave acetate for the treatment of intraocular pressure in open-angle glaucoma. This trial enrolled eighty nine subjects who were randomized to one of three arms: 7.5mg of anecortave acetate dosed with 0.25 mL of 30 mg/mL suspension, 15mg of anecortave acetate dosed with 0.5 mL of 30mg/mL suspension or 0.5 mL of placebo. Anecortave acetate was administered as an anterior juxtascleral depot in the sub-Tenon's space. One injection of drug or placebo was administered to each subject and intraocular pressure (IOP) was assessed at two weeks, six weeks and at month three; month three was predefined as the visit for primary efficacy. The primary efficacy endpoint was maintenance of IOP at or below the 21 mmHg. Both the 7.5 mg and 15 mg doses of anecortave acetate demonstrated statistically significant lower mean IOP than placebo at three months (p less than 0.05). Approximately 55% of subjects in both anecortave acetate arms reached the endpoint compared to 6.4% in the placebo arm. Treatment was determined to be safe and well tolerated. Based on the results, Alcon plans to commence phase II/III trials later in 2008.
February 20, 2006
Santen announced negative results of a phase II trial of olmesartan (DE-092), their angiotensin II receptor antagonist for the treatment of glaucoma. Trial data yielded no significant reduction in intra-ocular pressure, though a positive trend was noted at some doses. Further, no dose response was noted across the different concentrations of the drug. This dose ranging study enrolled patients in the US. Based on these results, the company announced plans to review the development program for olmesartan, pending the outcome of an ongoing phase II trial of the drug being conducted in Japan.
February 18, 2003
The University of Arizona reported positive results from a post-marketing study investigating Lumigan (bimatoprost ophthalmic solution), a synthetic prostamide analog for the treatment of glaucoma. Results showed that the average reduction in eye pressure was greater for subjects treated with Lumigan than with the alternative medication, Xalatan (latanoprost ophthalmic solution). Nearly three times as many subjects failed to respond to Xalatan than to Lumigan at certain measured time points. In addition, subjects treated with Lumigan reached a significantly lower mean intraocular pressure level than subjects in the Xalatan group. Itching was more common in subjects treated with Lumigan, and ocular burning was more common in subjects treated with Xalatan. Eyelash growth and red eye were reported with both medications. The randomized, blinded study enrolled 269 subjects with ocular hypertension and/or glaucoma.
May 13, 2002
Phase II trial results suggest that CAT-152 is safe and well tolerated in subjects undergoing surgery for glaucoma and cataract. In the trial, 56 subjects were randomized to receive either CAT-152 or placebo on the day of surgery, the day after surgery and a week after surgery. After 12 months, subjects treated with CAT-152 achieved lower IOP (14.4 mmHg mean value) than those receiving placebo (16.9 mmHg mean value). One hundred percent of CAT-152-treated subjects versus 85% of placebo-treated subjects achieved IOP below 22 mmHg. Additionally, four of 36 subjects receiving CAT-152 (11%) required topical medication to manage their IOP, compared to four of 20 subjects (20%) in the placebo group. CAT-152 is being developed by Cambridge Antibody Technology.