ProHeal Pharmaceuticals' PHP0101 Eye Drops Offer a Novel Therapeutic Option for Presbyopia
Pro-heal
Innovative Drug Developer
On October 23, 2023, the Center for Drug Evaluation accepted the presbyopia drug independently developed by Pro-heal Pharmaceuticals (Suzhou).PHP0101 Eye DropsThe new drug clinical application (acceptance numbers: CXHL2301153; CXHL2301154; CXHL2301155;). This is the second IND submission project by Pro-heal Pharmaceuticals after its establishment, and alsoChina's First Self-Developed Non-Pilocarpine Presbyopia Drug。
Presbyopia is a physiological phenomenon, an inevitable visual problem that occurs as people enter middle and old age, and one of the signals that the body is beginning to age. Presbyopia usually appears around the age of 38, with the peak incidence often occurring between 42 and 44 years old. In November 2020, China News Service reported that the population of presbyopia in China exceeded...390 million, accounting for nearlyThree-tenthsWith the improvement of modern people's quality of life, most patients with presbyopia are willing to seek diverse corrective methods to improve this situation, rather than solely relying on optical lenses and other similar mechanical devices for treatment and adjustment. Drug therapy, as a non-invasive treatment method, is of great significance for the treatment of presbyopia.
Overview of Drug Development
Currently, the presbyopia products that have been marketed and are under development in China and abroad are mainly based onSmall Aperture Effect, and develop products for the treatment of presbyopia. The small-aperture optical principle is the main research direction:By guiding light through a small aperture (whether artificial, induced, or natural), it is possible to block incident stray light and unfocused peripheral light, thereby extending the depth of field and minimizing the impact of corneal aberrations on vision.。
Figure1 Optometric Imaging
On October 28, 2021, Vuity (pilocarpine hydrochloride ophthalmic solution, 1.25%), developed by Allergan, a subsidiary of Abbvie, was approved for marketing by the U.S. FDA.®, is currently the world's first drug for treating presbyopia. Two years later, on October 19, 2023, Orasis Pharmaceuticals announced that its developed Qlosi (0.4% Pilocarpine Hydrochloride Ophthalmic Solution) received FDA approval for marketing in the United States. This medication needs to be used twice daily.
Currently, the main research in China is focused on引进 and仿制, primarily involving pilocarpine-class drugs, with no products yet on the market. Pilocarpine, carbachol, and aceclidine areM-Cholinergic Receptor Agonist, these eye drop products are allImproves near vision by contracting the pupil, thereby enhancing depth of field.
The figure below compares the effects of pilocarpine, carbachol, and aceclidine on lens accommodation and distant vision. By comparing the effects of these three cholinergic receptor agonists on lens accommodation,The results show that the greater the increase in lens thickness, the greater the impact on refractive adjustment, which can exacerbate myopia and reduce distant vision.Pilocarpine and carbachol, as widely-acting M-cholinergic receptor agonists, have a significant impact on lens thickness, greatly affecting distant vision. Aceclidine, another type of M-cholinergic receptor agonist, has a relatively smaller effect on lens thickness.
Figure2 The Effect of Cholinergic Receptor Agonists on Lens Accommodation and Distant Vision[1]
This shows that pilocarpine-like M-cholinergic receptor agonists have a strong effect on the ciliary muscle, which may cause spasms (potentially leading to headaches, impaired distance vision, retinal detachment, and uveitis), as well as result in the loss of distance vision. The pilocarpine molecule is only stable under low pH conditions and is also considered a controlled toxic substance. Aceclidine is unstable in aqueous solutions, making formulation development more challenging and relatively costly. Therefore,Finding a drug with good formulation stability, long-lasting effectiveness, fewer adverse reactions, rapid onset, and low cost is an ideal goal for developing presbyopia medications.
Advantages of PHP0101 Eye Drops
PHP0101 Eye DropsSpecifically acts on the iris, reducing the pupil size to create a pinhole effect and increasing depth of field; has almost no effect on the accommodation of the lens, and does not cause side effects such as headaches or pseudomyopia.After the application of PHP0101 eye drops at different concentrations in the experiment, the pupil diameter significantly decreased, while there was no noticeable change in lens thickness. In contrast, after the application of pilocarpine eye drops...Persistent and Significant Increase in Lens Thickness。
Figure 3: Change rate of lens thickness in each dose group and pilocarpine
PHP0101 Eye DropsFast-acting, long-lasting efficacyIn vivo pharmacodynamic experiments showed that the pupil constricted by 60% at 15 minutes after ocular administration, and the pupil still constricted by 50% at 8 hours, with an effective duration of over 8 hours.
PHP0101 Eye DropsEasy to penetrate the tear film and cornea, with higher drug distribution in the intraocular target tissues.After a single bilateral ocular administration in animals, PHP0101 was rapidly distributed in the tissues, reaching its peak around 30 minutes post-administration. During the experiment, all animals showed good tolerance to the PHP0101 eye drops, with no significant abnormal manifestations observed.
References:
[1]Ultrasonographic Study of the Effect of Different Myotics on the Eye Components, J. François and F. Goes, Ophthalmological Clinic of the University of Ghent (Director: Prof. J. François), Ghent.
Pro-heal Pharmaceuticals(Pro-heal Pharmaceuticals) was registered in 2019 and is located in the BioBAY Biomedical Industrial Park in Suzhou Industrial Park.The company is committed to developing ophthalmic and autoimmune disease drugs with innovative mechanisms of action to address unmet clinical needs., while also focusing on drug development in the field of rare diseases.
Its core founding team consists of returned overseas pharmaceutical professionals with over twenty years of experience in globally renowned pharmaceutical companies such as Allergan, Pfizer, and Johnson & Johnson. The team's expertise covers the entire process of drug development, having successfully developed multiple biologic macromolecule drugs and small-molecule chemical drugs.Pro-heal PharmaceuticalsHas advanced several pipeline projects from drug discovery and screening to the CMC stage in a relatively short period since its establishment.And the preclinical and clinical trial research stages.
The first Class I new drug independently developed in China for the treatment of thyroid-associated ophthalmopathy ——PHP1003Injection, Phase I clinical trial completed; TreatmentPresbyopia Drugs——PHP0101The new drug clinical application for the eye drops has been accepted by the Center for Drug Evaluation; a drug with an innovative mechanism of action for the treatment of wet age-related macular degeneration ——PHP0003The eye drops are currently in the CMC development stage; moreover, the company's product pipeline can be further expanded toThe treatment of autoimmune diseases such as uveitis, neuromyelitis optica spectrum disorders, Sjögren's syndrome, myasthenia gravis, systemic lupus erythematosus, and multiple sclerosis has broad application prospects.