On June 30, 2023, Bausch+Lomb (hereinafter: B+L) announced the acquisition of Xiidra rituxan and other ophthalmic assets of Novartis for $1.75 billion.B+L’s acquisition of Xiidra, shortly after receiving FDA approval for Miebo, demonstrates that the market for branded prescription dry eye treatments remains active.
In effect, B+L is building a complete portfolio of dry eye products. In addition to Meibo and Xiidra, they have acquired Blink Artificial Tears from Johnson & Johnson; Meibo for patients with evaporative/lid margin dysfunction, Xiidra for more inflammatory and fluid-deficient patients, and Blink Artificial Tears, which is by far the most ubiquitous means of dry eye relief. This series of layouts also reaffirms that dry eye is not just a disease, but rather a disease comprised of one or more comorbidities, each of which must be managed individually to achieve an acceptable clinical outcome.
Dry eye disease (DED), also known as dry eye syndrome (DES), dry keratoconjunctivitis (KCS), and dry keratitis, is a multifactorial, progressive disorder caused by abnormalities of the ocular surface tear film and inflammation of the ocular surface.
It is estimated that dry eye disease affects approximately 385 million people worldwide, more than 5% of the global population. (Gayton, 2009). In general, the prevalence of dry eye disease increases with age (Bron et al., 2017). In the United States, it is estimated that more than 3.2 million women over 50 years of age and 1.7 million men over 50 years of age have dry eye disease, and the prevalence is projected to increase by 40% by 2030 (Schaumberg et al., 2009; Schaumberg et al., 2013).
However, recent studies have found that the age of onset of dry eye disease is decreasing. The widespread use of cell phones, handheld computers, and reading devices has led to an increasing prevalence in younger age groups. And, glaucoma eye drops containing benzalkonium chloride preservative may also cause side effects that aggravate the symptoms of dry eye disease. This effect should not be underestimated, as the population ages, the number of glaucoma patients worldwide will approach 80 million (Quigley and Broman, 2006).
Growth Plus Reports estimates that the dry eye disease market is projected to grow at a CAGR of more than 5% to reach a global market of $8.92 billion by 2030 due to technological advancements in innovative drugs for dry eye disease, development of novel diagnostic tools, and increasing burden of dry eye disease.
The treatment of dry eye disease requires matching of regimens based on different subtypes as well as different stages of the disease. Current pharmacological therapies include supplementation of artificial tears, topical glucocorticoid eye drops and ointments, topical immunosuppressants, medications to stimulate lacrimal secretion, or surgical procedures, with the most commonly paired therapeutic agent being artificial tears. Since most artificial tears are OTC medications that can be purchased at the pharmacy, people are often unaware of the seriousness of dry eye disease.
In fact, there is still a lack of prescription medications that address this multifactorial disease and that work quickly for most patients.
According to VCBeat, more than 45 companies are currently developing dry eye medications and 50+ treatments have been explored. However, because dry eye is a multifactorial ocular surface disease, only some patients have shown efficacy with the products currently on the market.
Worldwide, pharmaceutical companies’ interest in the dry eye field originated in the 1990’s. In 1995, Ally Eye Drops developed by Japan’s Santen Pharmaceutical were approved for marketing, and its high sales volume quickly led to the development of the dry eye market, which led to the division of dry eye as an independent segment from the ophthalmology field.
In the following 10 years, ophthalmic giant companies such as Alcon/Novartis and Phonak have joined the competition to optimize the composition and dosage form of artificial tears to launch the next generation of products. Among them, Alcon’s early development of tetrahydrozoline hydrochloride eye drops Systane is still strong, in 2017 almost monopolized the European dry eye market, while the U.S. market because of the new mechanism of action of the drugs continue to market the existing “three-legged” pattern.
In 2002, Allergan (now AbbVie) developed a 0.05% cyclosporine preparation Restasis, which was approved in the United States by a narrow margin in clinical trials, breaking the blank situation of no effective drugs for moderate-to-severe dry eye. As the first-line drug for this indication and the only therapeutic variety at that time, cyclosporine became the mainstream product in the U.S. dry eye market with its unique immunosuppressive mechanism. At peak sales, it was generating more than $1.4 billion in annual revenues for Allergan. Subsequently, another anti-inflammatory small molecule, Xiidra, developed by Shire, entered the market in 2016. Xiidra quickly captured Restasis’ market share due to its faster onset of action.
Recently, a new therapeutic target, TRPM8 receptor agonists, has emerged for dry eye treatment. Evidence from clinical studies suggests that topical TRPM8 activation stimulates lacrimal function, reducing ocular discomfort and increasing tear production in patients with DED.
Currently, only two companies, Alcon and IVIEW, are each conducting research and development on this new target. the active ingredient in Alcon’s AR-15512 eye drops is a small molecule selective agonist of the proprietary transient receptor potential melastatin 8 (TRPM8) thermoreceptor, which is currently in Phase III development for the treatment of dry eye disease.
IVIEW’s IVW-1001 is a highly effective and selective TRPM8 agonist, which increases neural activity after topical application, and transmits to the central nervous system through the ophthalmic nerve (V1) of the trigeminal nerve to produce a cool and refreshing sensation, signaling and further brainstem output to the lacrimal glands to promote the secretion of basal tears (in order to increase the moistness of the ocular surface), and on the other hand, the cooling sensation itself can reduce ocular discomfort and eye pain and relieve the symptoms of dry eye disease.
Unlike traditional eye drops, IVW-1001 is administered by wiping the drug over the eyelid area, which allows the drug to effectively penetrate through the dermal surface to the eyelid and ultimately to the channel sites in the ocular surface tissue (cornea). This new method of drug delivery gives the innovative drug relationship a more diverse set of differentiating advantages.
The first is that it circumvents the inherent problem that only a small portion of the drug from an eye drop makes it to the tissues, while most of it is expelled through the nasolacrimal duct in less than a minute. In contrast, eyelid dosing creates conditions for slow release of the drug, allowing it to remain in the eye for a longer period of time, which in turn reduces the frequency of dosing (only two dosing sessions are expected to be required in a single day) and improves ease of use. It is also superior to traditional eye drops for elderly patients, patients with poor manual dexterity, patients wearing corneal contact lenses, and patients who wear false eyelashes or makeup during the day. What’s more, according to IVIEW’s study, the drug corresponds to a higher number of targets below the human eyelid, making slow penetration of the eyelid a more direct and precise route of administration.
Data from a proof-of-concept clinical trial (POC) conducted in South Korea showed that IVW-1001 works within one week of dosing and rapidly promotes tear secretion by the lacrimal gland, leading to direct symptomatic treatment and significant improvement in patient symptoms. The company aims to initiate a Phase I/II clinical trial for dry eye patients in early 2024.
Inclusion in health insurance is an effective means of raising awareness of the disease. IVIEWIVIEW Therapeutics Inc. was founded in late 2015 in Pennsylvania, U.S.A., by pharmaceutical industry veterans Dr. Bo Liang and Dr. John J. Baldwin, with the goal of improving patient vision through the development of innovative ophthalmic therapies.
Dr. Bo Liang, a former senior scientist at Pharmacopeia, founded CLS Pharmaceuticals with two ophthalmologists in New York, USA in 2006. The innovative eye drug they invented was acquired by Shire Shire Pharmaceuticals for $300 million in cash in 2015.Dr. John J. Baldwin’s 30 years at Merck & Co. resulted in the development of numerous innovative medicines, including Trusopt for the management of glaucoma, as well as Cosopt, Pepcid AC, and others. He is also the founder of Shanghai WuXi AppTec and Shanghai Hualing Pharmaceuticals, and is an innovative drug discovery expert inducted into the American Chemical Society’s Medicinal Chemistry Hall of Fame.
IVIEW has now assembled full-time innovative drug development teams in both the US and China, with a 10,000-foot research center in New Jersey, US, and a nearly 1,000-square-foot research center in Hengqin, Zhuhai, China. The company’s ophthalmic drug development consultant team has more than 25 years of ophthalmic drug development experience from major pharmaceutical companies such as Novartis, Pfizer, GSK, Alcon, etc., and is also equipped with a SAB advisory board consisting of renowned pharmaceutical experts, scientists, and ophthalmologists from research institutes and pharmaceutical companies such as the NIH, Stanford, Duke, Berkeley, Columbia, and Merck Sharp & Dohme.
For the Avec team, which has rich overseas clinical experience and FDA communication experience, entering the Chinese market has certain basic advantages, but there are also many special challenges to overcome. On the one hand, the start-up period for clinical trials in China is longer and there are more reviewing organizations. On the other hand, unlike the European and American markets, the treatment of dry eye in China is still stuck in the use of artificial tears, and the domestic market is at a blank stage for drugs for the treatment of moderate to severe dry eye. What’s more, patients and doctors are still relatively unaware of dry eye, and have a relatively weak awareness of the need to receive prescription medication to prevent the disease from developing and worsening.
Dr. Liang Bo, Co-Founder, Chairman and CEO of IVIEW, believes that the inclusion of medical insurance will be the most effective way to reverse this situation. Therefore, increasing communication with relevant authorities and regulators and promoting market education by facilitating the success of health insurance negotiations will be one of IVIEW’s future endeavors.
Diversified commercial cooperation overseas and accelerated commercialization at home. Although ophthalmology is a specialized field in the pharmaceutical industry, ophthalmic diseases cover a wide range of areas and have a high patient base, coupled with the growing trend of ophthalmic diseases as a result of the increasing utilization of electronic products and the social phenomenon of an aging population.
China over the past six years there are only seven new ophthalmic drugs on the market and are imported products, clinical ophthalmic drugs are far from meeting clinical needs, therefore, the ophthalmic drug industry is in urgent need of innovative, with better efficacy, can fill the market demand for ophthalmic drugs. Over the past two to three years, domestic and foreign institutions have increased investment in ophthalmic innovative drug research and development, but also broaden the idea of ophthalmic therapeutics, small molecule drugs, different therapeutic mechanisms, gene therapy, antibody drugs; a variety of innovative ophthalmic drug delivery system research and development, breakthroughs in the traditional limitations of ophthalmic drug delivery, but also show a good market outlook.
In the future, while accelerating the development of innovative products, IVIEW will be committed to accelerating the clinical development of its existing product pipeline, and intends to enter the stage of cooperation and commercialization with large companies. The Company’s IVIEW-1201 clinical phase II trials for the treatment of both viral conjunctivitis and bacterial conjunctivitis will be completed by the end of 2023, and with the support of clinical data, the Company will advance to clinical phase III in 2024, while the related business development will be launched at the same time. IVW-1001, an innovative compound for the treatment of dry eye disease, will start clinical phase IIa trial in 2024 to verify its safety and efficacy. In addition, the Company will concurrently develop innovative compounds for the treatment of myopia (PIND application to the FDA is planned to be submitted in 2024) and innovative gene therapies for the treatment of glaucoma (IIT clinical launch in the first half of 2024).