As we expected in our previous articles, Today, Aerie Pharmaceuticals (AERI) came up with great news about its glaucoma treatment. The stock surged ….
On February 18, 2016, Under News & Comments, we wrote an article titled “Aerie Pharmaceuticals: Novel Glaucoma Eye Drops Confirm their Superiority”. The article also referred to a Prohost previous article written on February 4, 2015 and tittled “Aerie Pharmaceuticals is speeding towards improving the treatment of glaucoma” we wrote:
“Aerie Pharmaceuticals has eye drops that could become a game changer in the management of glaucoma. The firm’s lead drug, Rhopressa™, is a one drop once-daily having triple action that might bring life to over two decades of paralysis in Glaucoma treatments.”
Rhopressa™ inhibits Rho Kinase (ROCK) and the norepinephrine transporter (NET). Both are novel biochemical targets for drugs that aim at lowering intraocular pressure (IOP).
To refresh our readers’ memory, we reiterated then as we reiterate now describing Aerie Pharmaceuticals (AERI) as follows:
Aerie is a development-stage pharmaceutical Company focused on eye diseases, mainly glaucoma. The firm’s lead product candidate, Rhopressa™, is a once-daily triple-action eye drops that’s demonstrating ability to lower intraocular pressure (IOP) in patients with open-angle glaucoma. Aerie second glaucoma product, Roclatan, is a single quadruple-action eye drops. It is a combination of Rhopressa plus the marketed eye drops latanoprost. Roclatan is to be administered once-daily.
The article described two Phase 3 registration trials being conducted at the time in the U.S. to demonstrate non-inferiority of lowering IOP with Rhopressa compared to the conventional drug timolol.
Why We Are Enthusiastic
The enthusiasm towards Aerie’s drugs emanates from several facts starting with a successful Phase 2b trials confirming Rhopressa’s obvious advantages over theconventional non-surgical treatments for glaucoma. These advantages comprise the following:
1. Patients’ compliance: The fact that the product is a once a day eye drops helps the patients comply, which is a strict necessity for a successful control of intraocular pressure (IOP).
2. Reduction of IOP via multiple mechanisms of actions: Inhibiting Rho Kinase (ROCK) and norepiephrine transporter (NET), Rhopressa reduces IOP through several separate mechanisms of actions. ROCK inhibition increases fluid outflow through the trabecular meshwork (TM), which accounts for 80% of fluid drainage from the eye. It also reduces episcleral venous pressure (EVP), which represents the pressure of the blood in the episcleral veins of the eye where eye fluid drains into the bloodstream. NET inhibition, on the other hand reduces the production of eye fluid. The multiple mechanisms of Rhopressa’s action lead to a strong intraocular pressure (IOP)-lowering effect.
3. Phase 2 trial promising results: Results from Phase 2b clinical trial, with Rhopressa demonstrated mean IOP reductions of 5.7 and 6.2 mmHg (millimeters of mercury) on days 28 and 14, respectively. Important to note that studies have shown that a sustained 5 mmHg reduction in IOP reduces by around 50% the risk of disease progression.
3. Favorable Tolerability Profile: Currently marketed glaucoma drugs have several adverse effects, including ocular allergic reaction, itching of the eye, iris color change, orbital tissue discoloration, unusual taste and hyperemia. Currently marketed non-PGA drugs have also systemic side effects, including among others, lethargy, reduced heart rate, Stevens Johnson syndrome and blood dyscrasias. The most widely prescribed non-PGA drug, timolol, has warnings that include bronchospasm, arrhythmia and heart failure.
In Phase 2a and 2b clinical trials where 209 patients were exposed to Rhopressa™. The main adverse effect for Aerie drugs was mild hyperemia, which is a cosmetic asymptomatic redness of the eye. Hyperemia is a common tolerability finding also associated with PGAs.
4. Rhopressa™ targets the trabecular meshwork, the diseased tissue responsible for elevated intra ocular pressure in glaucoma and the eye’s primary drain, whereas commonly prescribed PGAs and non-PGAs target the secondary drain and the fluid production in the eye, respectively.
Prohost Decision at the Time
Based on the above, we believe the odds of successful outcome of phase 3 trials exceed those of possible failure, especially that Aeri’s drugs have demonstrated clear safety compared to the conventional treatments.
Regarding efficacy, the level of IOP reduction expected to be achieved by Rhopressa would be equal to or exceed that of all currently marketed non-PGA products, both results are sufficient tor the drug to be approved knowing in fact that the primary endpoint of the trials is non-inferiority.
Safety of Aerie’s drugs offers a great advantage against the conventional treatments
For the 80% of glaucoma patients with low to moderately elevated IOPs, we expect the phase 3 results to superiority over the currently marketed PGA products in lowering the IOP.
Published studies have indicated that the currently marketed PGA and non-PGA products for Glaucoma do not lower IOP as effectively in patients with low to moderately elevated baseline IOPs relative to patients with higher baseline IOPs.
Phase 2b clinical trial with Rhopressa demonstrate a reduction in IOP across all baseline IOPs tested in the trial. The results of a preclinical in vivo study reported one year ago, suggest that this differentiated effect may be attributable to the ability of Rhopressa™ to lower EVP.
Quadruple-action Roclatan™, a single-drop fixed-dose combination of Rhopressa™ and latanoprost, lowers IOP through the same three MOAs as Rhopressa™ and, as a fourth MOA, through the ability of latanoprost to increase fluid outflow through the uveoscleral pathway, the eye’s secondary drain.
Prohost Statement: If approved, Roclatan™ would be the only glaucoma product that covers all currently known intraocular pressure-lowering mechanisms of actions. This also means that Roclatan has the potential to provide a greater IOP-lowering effect than any currently marketed glaucoma product. Therefore, we believe Roclatan™ could compete in both the PGA and non-PGA markets, becoming the product of choice for patients requiring maximal IOP lowering.
1. Efficacy Superior to Latanoprost – Phase 2b clinical trial results with Roclatan™ demonstrate the drug has achieved its primary efficacy endpoint of statistically significant superiority over each of its components on day 29. The trial included 297 patients with non-medicated entry IOPs that ranged from 22 to 36 mmHg. Roclatan™ lowered mean diurnal IOP from 25.1 mmHg at baseline to 16.5 mmHg on day 29, a 34 percent decrease in IOP.
2. Roclatan’s mean diurnal IOP reduction was approximately 2 mm Hg greater than with latanoprost.
We wrote: We are optimistic about Aeries’s drugs for glaucoma and we believe that the firm has done a great job developing the two products Rhopressa™ and Roclatan, which if approved (we believe they will be approved) the firm’s equally important task, i.e., to market these drugs by itself in the U.S. will begin. Indeed that’s what the firm intends to do in the United States, while bringing other marketers for other countries, including Japan and the European Union.
We were expecting efficacy results for Rocket 2 clinical results in mid 2015 and of Rocket 1 in the middle of second-quarter 2015 and the filing for approval in 2016. This is a good scientific study, regarding a successful development of far-reaching treatments for glaucoma.
We are optimistic, yet, we will be more comfortable learning more about the firm’s plans for the drugs’ marketing in the U.S. by itself.
We decided to buy the minimum amount of stock at the current price prior to the clinical trial results. We will accumulate on weaknesses going forward towards the results, then the filing for approval and then the approval.
Aerie, we believe, is a candidate for acquisition by one of the big firms specialized in eye diseases, especially glaucoma.
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On September 17, 2015, under the title, “Aerie Pharmaceuticals: Another Step Forward Towards the Approval of a Promising Glaucoma Drug”, we again wrote:
Aerie Pharmaceuticals (AERI) reported successful results of its second Phase 3 trial for Rhopressa™ — a novel once-daily, triple-action eye drops for glaucoma. The trial achieved its primary efficacy endpoint demonstrating non-inferiority of Rhopressa™ compared to the most widely used comparator drug timolol.
Rhopressa™ Phase 3 Highlights for Rocket 2: Dosed once-daily and twice-daily, Rhopressa™, achieved its primary efficacy endpoint demonstrating non-inferiority compared to twice-daily timolol. The primary efficacy endpoint evaluated subjects with pre-study baseline IOPs of above 20 to below 25 mmHg (millimeters of mercury).
You can read the rest of that article posted on September 17, 2015 under News & Comments at the Prohost Website.
IN TODAY’S NEWS
Reclatan Is a Winner. Aerie Pharmaceuticals Reports Positive Roclatan™Results
RoclatanTM Successfully Achieves Primary Efficacy Endpoint in Mercury 1 Study
Conference Call and Webcast Today, September 14, at 5:00 p.m. ET
Aerie Pharmaceuticals reported the successful 90-day primary efficacy results of its 12-month Phase 3 “Mercury 1” clinical trial for its fixed-dose combination product candidate, RoclatanTM.
The study achieved its primary efficacy endpoint — statistically superior over each of its ingredient including Aerie product candidate RhopressaTM and latanoprost, all of which were dosed once daily in the evening.
The study evaluated patients having maximum baseline intraocular pressures (IOPs) ranging from above 20 to below 36 mmHg (millimeters of mercury). The IOP-lowering effect of RoclatanTM was 1 to 3 mmHg greater than monotherapy with either latanoprost or RhopressaTM throughout the duration of the study.
The Stock surged
Aerie will hold an “Investor Day” in New York City on October 5, 2016 to cover further details from the Mercury 1 trial and to provide a general business update.
From among what Dr.. Vicente Anido, Jr., Ph.D., Chairman and Chief Executive Officer at Aerie said,
“We are very pleased by these RoclatanTM 90-day efficacy results from the Mercury 1 clinical trial.”
“Topline efficacy demonstrated in this trial clearly reconfirms the potential for RoclatanTM to become the most efficacious IOP-lowering therapy to enter the market, if approved.
“If Mercury 1 and 2 are successful, we expect to file the NDA for RoclatanTM near year-end 2017.”
“RhopressaTM arm demonstrated high levels of efficacy across the full range of baseline IOPs studied, and the efficacy was maintained for the 90-day period.”
“Importantly, RhopressaTM demonstrated comparable levels of IOP lowering to latanoprost at baseline IOPs ranging from 20 to 25 mmHg in Mercury 1. This performance for RhopressaTM is consistent with levels observed in the previous Phase 2b trials for RhopressaTM and RoclatanTM.”
Richard A. Lewis, M.D., Aerie’s Chief Medical Officer added, “Once-daily RoclatanTMhas shown a degree of IOP lowering in Mercury 1 that is quite impressive, especially when considering its ability to bring patient pressures down to levels as low as 8 to 14 mmHg. The safety profile of RoclatanTM observed thus far in Mercury 1 points to a safe and tolerable product.”
AERI Pharmaceutical’s stock is trading now at $33 Up around $12. Like always, negative investors will have something to say to let investors take profit and run. Although we know that a lot can happen from now until the filing for approval in a late quarter of 2017, we will continue what e decided upon in early 2016, which is to accumulate on weaknesses.
Do we have a target?
Yes, we always had one in mind. It is $50. This number is based on the market’s volume for Glaucoma and the advantages of AERI drugs compared to the currently marketed drugs.
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