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Aerie Pharmaceuticals announced Tuesday positive topline results for the Japan-based, phase 3 trial evaluating netarsudil ophthalmic solution 0.02% (netarsudil 0.02%) versus ripasudil hydrochloride hydrate ophthalmic solution 0.4% (ripasudil 0.4%).

As Rho kinase (ROCK) inhibitors, netarsudil 0.02% — known as Rhopressa® in the U.S. — and ripasudil 0.4% — known as Rhokiinsa® in the EU — are intended to treat open-angle glaucoma (OAG) and elevated intraocular pressure (IOP), 

The clinical trial included a single-masked comparison of netarsudil 0.02% dosed once daily versus ripasudil 0.4% dosed twice daily in 245 participants for four weeks.

Of the 245 patients, 122 received netarsudil 0.02% while 123 received ripasudil 0.4%. In total, 238 participants completed the study.

Trial results revealed that netarsudil 0.02% once daily was superior to ripasudil 0.4% daily in lowering at week 4 (p<0.0001), the primary endpoint for the study, the company reported.

The baseline mean diurnal IOP was 20.5 and 20.8 mmHg in the netarsudil 0.02% and ripasudil 0.4% arm, respectively. 

Additionally, the mean diurnal IOP was significantly lower (16.0 mmHg) in the netarsudil 0.02% group compared to the ripasudil 0.4% group (17.7 mmHg, p<0.0001), the company stated.

At four weeks, netarsudil 0.02% reduced mean diurnal IOP by 4.7 mmHg (22.6%) from baseline compared to 3.0 mmHg (14.3%) with ripasudil 0.4% (p<0.0001), according to the company.

Aerie reported that both medications were well-tolerated, with the most common treatment emergent adverse event being conjunctival hyperemia (54.9% of subjects with netarsudil 0.02%; 62.6% of subjects with ripasudil 0.4%).

The trial was conducted in alignment with Japan’s Medical Devices Agency (PMDA) in anticipation of a potential regulatory submission of netarsudil 0.02% in Japan.

We believe that the statistically superior IOP-lowering of netarsudil versus the comparator in our study may suggest a very bright future for our product in Japan, a market where the comparator product is the only rho-kinase inhibitor commercially available,” said Benjamin F. McGraw, III, PharmD, Aerie’s interim executive chairman. “The IOP-lowering with netarsudil was consistent with that seen in the previous Phase 2 study conducted in Japan as well as in our ROCKET and MERCURY studies conducted in the United States for Rhopressa® and Rocklatan®, respectively.”

Articles

Aerie Pharmaceuticals announced Tuesday positive topline results for the phase 3 trial evaluating netarsudil 0.02% versus ripasudil 0.4% for the treatment of open-angle glaucoma and elevated IOP.









Aerie reports positive phase 3 results for netarsudil 0.02% vs ripasudil 0.4% in lowering IOP

A study by a team of University of Illinois Chicago investigators has uncovered a mechanism that stops the herpes simplex virus 1 from causing serious brain damage and death.

Investigators discovered a function of a protein complex, mammalian target of rapamycin complex 2, in an antiviral defense mechanism. 

This protein complex limits HSV-1 virus infection through rapid activation of antiviral immunity and protects the host by preventing encephalitis — brain inflammation — and possible death due to HSV-1 infection.

The paper was published recently in the journal 

 The research was performed by UIC researchers in the laboratory led by Deepak Shukla, PhD, the Marion H. Schenk Esq. Professor in Ophthalmology for Research of the Aging Eye, and vice chair for research at UIC. 

Ocular herpes infection is a leading cause of infectious blindness and can lead to lethal brain infections. 

After a primary infection, HSV-1 hides in neuronal tissues and reactivates under immune suppressive conditions that may cause encephalitis, leading to permanent brain damage, memory loss or even death. 

Herpes is a common infection, even in healthy individuals, and is rarely lethal. To understand how antiviral defense mechanisms could work, UIC researchers studied mTORC2, Shukla said.

Using genetically modified mice models, investigators uncovered the importance of mTORC2 in activation of innate- and virus-adaptive immunity during ocular HSV-1 infection.

According to Shukla, animals with a lack of functional mTORC2 were found to show significant loss of immune activation and more spread of virus to neuronal tissues.

“Functional mTORC2 limits the virus spread from ocular to neuronal tissues by supporting the production of antiviral cytokines and driving immune cells to quickly identify HSV-1 infected cells,” Shukla said. “MTORC2 also protects the ocular and neuronal cells from virus-induced cell death offering protection to neuronal tissue.”

In order to combat lifelong HSV-1 infection, it is essential to uncover the role of key cellular proteins and modulate their function to stop the virus from replicating and causing damage, according to Rahul Suryawanshi, the study’s lead author, a former postdoctoral trainee of Shukla, now at the Gladstone Institutes, San Francisco.

During herpes infection, mTORC2 activates cell survival machinery in ocular and neuronal tissues. 

This restricts a programmed cell death mechanism, which limits virus spread but, at the same time, is detrimental to neuronal cells, Suryawanshi said.

“The animal experiments highlight the importance of using neuronal cell death inhibitors during viral encephalitis that may mimic and/or improve mTORC2 functions and prevent brain injuries,” said Chandrashekhar Patil, a co-author of the study and a visiting scholar at UIC’s department of ophthalmology and visual sciences.

Shukla said the study explains that the pro-survival functions of mTORC2 may not be limited to viral infections. They are likely to be applicable to many other diseases.

“Our study will motivate other researchers to investigate mTORC2 in neurodegenerative disorders and diseases as well,” Shukla concluded.

Additional authors are Alexander Agelidis, Raghuram Koganti, Joshua M. Ames, Lulia Koujah, Tejabhiram Yadavalli, and Krishnaraju Madavaraju, all of UIC, and Lisa M. Shantz of the University of Connecticut.

This research was supported by the National Institutes of Health and National Eye Institute grants and Illinois Society for Prevention of Blindness.


1 Suryawanshi, R.K., Patil, C.D., Agelidis, A. 

 mTORC2 confers neuroprotection and potentiates immunity during virus infection. 

 12, 6020 (2021). https://doi.org/10.1038/s41467-021-26260-5

Ocular herpes infection is a leading cause of infectious blindness and can lead to lethal brain infections. Using genetically modified mice models, investigators uncovered the importance of mTORC2 in activation of innate- and virus-adaptive immunity during ocular HSV-1 infection. 

Investigators studying ocular herpes identify protein that reduces risk of fatal HSV-1 infection, prevents brain damage

In honor of World Sight Day, staff from our parent company, MJH Life Sciences, share their perspectives on the significance of vision in their lives.

Oct. 14 marks the 21st World Sight Day, an annual day of awareness, held on the second Thursday of October, to focus global attention on blindness and vision impairment. 

Coordinated by the International Agency for the Prevention of Blindness (IAPB), this year’s call is for everyone to “Love Your Eyes.”

As part of its efforts, the IAPB and its members are working together to increase public awareness on vision issues and blindness, calling for a focus on vision issues and eye health.

The IAPB launched its campaign over the summer in advance of World Sight Day to urge people to commit to vision screenings. 

As part of its campaign, it has been urging eye care professionals, including ophthalmologists and optometrists, to get involved.

“Almost everyone on the planet will experience an eye health issue in their lifetime, yet more than a billion people worldwide do not have access to eye care services,” Peter Holland, CEO of IAPB said in a statement. “This is a global issue, but one that starts with us.”

Today, IAPB is promoting a global challenge to unite the world, bringing people across the globe together to have their eyes tested.

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In honor of World Sight Day, staff from our parent company, MJH Life Sciences, share their perspectives on the significance of vision in their lives. 

What does World Sight Day mean to you?

Oxurion NV announced Wednesday the first patient to be dosed in the INTEGRAL phase 2 clinical study evaluating THR-687 as a treatment for patients with diabetic macular edema (DME).

The INTEGRAL study is a randomized, multicenter trial that is the first in which multiple intravitreal injections of THR-687 will be administered in humans, 

INTEGRAL intends to evaluate two parts: two dose levels of THR-687 injections (Part A), and if a success, then assess the efficacy and safety of THR-687 in comparison to aflibercept, for the treatment of DME (Part B).

The company reports that Part A of the study is being conducted in treatment naïve subjects to select the optimal THR-687 dose level to be assessed in Part B.

Part B will be conducted in both treatment naïve and treatment experienced subjects to evaluate the efficacy and safety of THR-687 compared to aflibercept, according to the news release.

The company reports that Part B’s primary efficacy endpoint is the changing in best-corrected visual acuity (BCVA) from baseline to Month 3.

Dose selection decision after Part A is estimated for the first half of 2022, while topline data from Part B to follow in the second half of 2023.

The latest development comes following the positive data from a phase 1, open-label, multi-center, single-dose escalation study assessing safety of THR-687 for DME in the form of a single intravitreal injection of 3 dose levels: 0.4 mg, 1.0 mg, and 2.5 mg.

Results from this study showed THR-687 was safe and well-tolerated.

In addition to DME, THR-687 shows potential as a treatment for wet age-related macular degeneration (AMD) and retinal vein occlusion (RVO).

Oxurion NV announced Wednesday the first patient to be dosed in the INTEGRAL phase 2 clinical study evaluating THR-687 as a treatment for patients with DME.

OT Staff Reports

Articles

Investigators studying ocular herpes identify protein that reduces risk of fatal HSV-1 infection, prevents brain damage

What does World Sight Day mean to you?

Oxurion NV doses first patient in study of THR-687 as DME treatment

Aerie reports positive phase 3 results for netarsudil 0.02% vs ripasudil 0.4% in lowering IOP