London-based biotech TopiVert, although invisible, intends to shake up Allergan, Shire in the huge dry-eye space.

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The News:

TopiVert Pharma Ltd., a clinical-stage biotechnology company developing narrow spectrum kinase inhibitors (NSKIs) for chronic inflammatory gastrointestinal (GI) and ocular diseases, has announced results from a Phase 1/2a proof of concept study of its TOP1630 ophthalmic solution.

TopiVert’s TOP1630 is a treatment for the dry-eye syndrome (DES) which improved multiple symptom and sign endpoints in both an environmental setting and in the Controlled Adverse Environment challenge, according to Pharmaceutical Daily. Furthermore, the company said that TOP1630 showed excellent safety and placebo-like tolerability and comfort profiles.

TopiVert said that in the study, TOP1630 delivered statistically significant results across multiple signs and symptoms endpoints in DES starting at day 15, the first study assessment point. All analyses reported were pre-specified.

Symptoms showing significant improvements for TOP1630 versus placebo included improvement in the worst DES symptoms: ocular discomfort, grittiness/foreign body sensation and ocular pain. All regions of ocular surface, corneal sum and conjunctival sum staining improved with TOP1630 compared to placebo.

There were no safety findings, with TOP1630 shown to be safe and well tolerated with a placebo-like profile. Importantly, this included no noticeable application-site pain and discomfort.

Professor John Sheppard, Professor of Ophthalmology, Eastern Virginia Medical School said that the study showed consistent effects across both signs and symptoms, with placebo-like tolerability.

He said that those characteristics define “a very promising benefit-risk profile, and therefore highly likely to prove beneficial to patients and desirable for prescribing eye care providers.”

Ajay Duggal, TopiVert’s chief medical officer, said:

“We believe that the consistency of effect demonstrated across a range of sign and symptom endpoints, from multiple assessment scales and all from pre-specified analyses, coupled with the placebo-like tolerability profile sets a new benchmark for DES treatments. This exciting program is now ready for late stage development in an area of high unmet medical need.”

DES is a common inflammatory disorder of the front of the eye associated with considerable morbidity. A major unmet medical need remains for a more effective and better tolerated therapy for this debilitating disorder which affects over 300 million worldwide.

According to TopiVert, TOP1630 “has the potential to provide rapid symptomatic relief together with long-term efficacy in the treatment of the signs and symptoms of DES.”

Steve’s Take:

If it’s one thing I admire in senior management of a startup–especially in a crowded, lucrative disease space–it’s the unshakeable attitude, widely attributed to Michelangelo, that, “It’s better to aim high and fall short, than aim low and reach your mark.”

Steve's Take: @Topivert has an admirable go-getter attitude in the #dryeye market, but they face stiff competition from @Allergan and others Click To Tweet

TopiVert epitomizes that philosophy. This DES upstart released the results of a clinical trial it believes yielded “the best proof of concept data in dry-eye syndrome.”

Based in London, the biotech is trying to enter the $3 billion market for DES with a drug possessing the potential to surpass other treatment options currently available for patients with this condition.

“Most people are just not aware of the huge unmet medical need there is,” said Ajay Duggal, CMO of TopiVert. “There are 40 million people with the disease in the US alone, and research has revealed dry-eye syndrome impacts quality of life as much as angina.”

As he explains, many patients use over-the-counter eye drops to address the symptoms. But they do not target the cause of the disease, which is an inflammatory process, notes. The leading prescription medicines are Allergan PLC’s (Dublin IRL) Restasis and Shire PLC’s (Dublin) Xiidra, but both have limited efficacy and come with several side effects, including irritation of the eyes, of all things!

To address this situation, TopiVert is using a technology called narrow spectrum kinase inhibitors (NSKIs).

“They work by targeting a range of kinases, which are molecules involved in the inflammatory response,” explains Nick Staples, the company’s chief business officer.

Kinase inhibitors are commonly used in cancer therapy, but they often cause side effects because kinases are involved in many other physiological processes. To avoid that, TopiVert targets a narrow selection of kinases and delivers the drug locally to the eye.

In a first Phase 1/2a clinical trial where 60 patients were treated with either placebo or TopiVert’s therapy for dry-eye syndrome, TOP1630, the company’s strategy seems to have proved successful, says Labiotech.

The therapy was as safe and well tolerated as the placebo. But most importantly, the efficacy data indicate the drug might be superior to what is currently on the market. These effects were further improved after 29 days on many of the measurements.

CMO Duggal is confident that TopiVert will be able to reproduce these results in the next clinical trial. If the results are confirmed there, it would allow the company to seek regulatory approval to market the med.

Bottom Line:

Let’s return to today, and to reality.

Back in September, I wrote about how Allergan announced that it made a deal with a New York state American Indian tribe to help protect blockbuster Restasis from competition, using the tribe’s sovereign immunity as a shield against patent challenges. The deal–the first such move by Allergan and, in the pharmaceutical industry, an unusual one at best–has unleashed a firestorm of criticism, including from lawmakers.

Restasis, a dry-eye medication used for eye inflammation, is a powerhouse for Allergan. Last year, the medication brought in a whopping $1.4 billion in revenue, second only to Allergan’s top product, Botox.

Dry-eye disease, characterized by chronic pain, dry-eyes, eye discomfort and variable vision, is “maybe one of the most common reasons people seek eye care,” said Dr. Penny Asbell, director of the cornea and refractive surgery service at The Mount Sinai Hospital.

Restasis is expensive, with an average retail price of $574 for a 60-vial package, according to price comparison website GoodRx.

TopiVert has been patiently plugging away with its hoped-for breakthrough for dry-eye. But there’s plenty of current competition to top med Restasis. Recent entrants into the race include Shire’s Xiidra, Novartis AG’s Lubris and Sun Pharmaceutical Industries Ltd.’s Seciera.

TopiVert’s Duggal says he expects the company to be seeking approval, “Something that could happen as soon as 2021.”

That’s an optimistic timeframe for additional clinical success. But investors are impatient, given how packed the field of contenders is for a piece of the dry-eye pie. The clock is ticking.

Still, Duggal’s confidence embodies that philosophy about aiming high. I admire it. Stay tuned.

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