New Delhi: Last week, the Central Drugs Standard Control Organisation (CDSCO), India’s apex drug regulator, revoked the authorisation issued to Mumbai-based Entod Pharmaceuticals to manufacture and market an eye drop, which was projected to replace the need for reading glasses in middle-aged people.
The decision came weeks after the firm received regulatory approval to launch and sell PresVu, marking the first such instance, wherein the permission to launch a new drug was revoked based on its marketing campaign and possible risk to public health.
ThePrint explains the development, the controversy and safety concerns around pilocarpine, the active ingredient used in the eye drop.
Similar drug in use in the US
PresVu, which was slated to become available in pharmacies across India from October this year, contains pilocarpine hydrochloride 1.25 percent. A similar drug, sold under the brand name Vuity by Dublin-based biotech company Allergan—part of pharmaceutical major AbbVie—has been in use in the United States since late 2021.
In a press release issued 3 September, Entod Pharmaceuticals had said that PresVu is the first eye drop in India specifically developed to reduce dependency on reading glasses for individuals affected by presbyopia, a common age-related blurry vision condition that typically impacts those over 40.
“The proprietary formula not only gets rid of reading glasses, but also helps the patient lubricate their eyes as a side benefit. These eye drops utilise advanced dynamic buffer technology to swiftly adapt to tear pH, ensuring consistent efficacy and safety for extended use, keeping in mind that such drops will be used for years at a stretch,” it said.
Entod Pharmaceuticals CEO Nikkhil K. Masurkar had stressed that the eye drop should be used only when prescribed by an ophthalmologist.
But in an order issued last week, the CDSCO revoked the marketing and sale authorisation to the eye drop, saying that Entod was violating conditions of marketing permission by falsely projecting it as a replacement for reading glasses.
The order, undersigned by Drugs Controller General of India (DCGI) Rajeev Singh Raghuvanshi, also said that the drugmaker failed to respond satisfactorily to the queries raised, and instead tried to “justify the claims” made by it to the press and on social media.
On its part, Entod strongly objected to the decision, saying that all facts disclosed to the media were strictly on the basis of the recent DCGI approval for treatment of presbyopia in adults and the results of the phase 3 clinical trial conducted by it in India.
In a statement last Wednesday, Masurkar said that the firm will challenge the decision in the court of law.
Announcing a new product launch to the media is a routine industry practice followed by all pharmaceutical companies in India and in the recent past, many such announcements have been made, he added.
He underlined that the suspension order made no reference to any specific violation of the Drugs and Cosmetics Act, 1940 for the action taken against the pharmaceutical firm.
“The logic applied here is the contents of our press release, which has described the application of this new drug for the benefit of the lay press in more verbose terms than the exact wording of the approved indication which is—treatment of Presbyopia,” Masurkar’s statement read.
It added that in many such press announcements made by pharmaceutical giants, which are present on their websites, there are additional descriptions about the products and conditions beyond the exact approved indications.
Safety concerns around pilocarpine
Pilocarpine, extracted from plants, has been used for decades to reduce eye pressure and treat dry mouth. As an eye drop, it is used to manage angle-closure glaucoma (sudden increase in eye pressure when the iris bulges and blocks the drain of fluids from the eye), ocular hypertension, and to constrict the pupil after dilation.
However, due to its side effects, it is no longer typically used for long-term management.
In a scientific commentary published in The Indian Journal of Ophthalmology last year, Dr Tarannum Mansoori, a senior eye specialist with Anand Eye Institute in Hyderabad, had written that continuous and regular use of pilocarpine 1.25 percent for the treatment of presbyopia needs to address some of the questions on adverse effects, which may not become evident within 30 days—the duration of the clinical trial.
Pilocarpine‑induced miosis (constriction of pupil) begins 15-30 minutes after application and lasts for 4 to 8 hours.
Hence, a single dose every morning will not be sufficient to sustain effects on near vision till the evening, the paper had said. It added that patients with lenticular opacities (irregularity in ordered arrangement of lens fibres necessary to maintain lens transparency) will have decreased vision in dim illumination, and should be warned of the dangers of night driving, if they use the eye drop in the evening.
Also, there can be changes in distance vision due to fluctuating myopic shifts in refraction (increase in myopia or near-sightedness) and hence, one needs to see whether an improvement in near vision is at the cost of compromised distance vision.
The direct‑acting cholinergic drug (pharmaceutical agents that act on neurotransmitter acetylcholine, which stimulates pupil muscles) can alter lens permeability, leading to a shift in lens cations and water accumulation, and changes in the intraocular metabolism, the paper said, adding that the chemical’s use may accelerate lens opacity formation.
The long‑term adverse effects of the drug should be kept in mind, Mansoori had stressed in the paper.
Pilocarpine binds to melanin in the iris and ciliary body, and hence, iris colour may influence the drug’s desired response, the paper had said, adding that patients with darkly pigmented irides may require a higher concentration of pilocarpine to avail its maximum effect.
The All India Ophthalmological Society (AIOS) also raised concerns on the regulatory approval for PresVu in India.
Speaking to ThePrint, Dr Sreeni Edakhlon, a member of the AIOS management committee, said that pilocarpine is mostly not prescribed for treating glaucoma.
“Far safer drugs are now available to treat glaucoma,” he said. “There have been safety concerns around Vuity in the US, too and it is not widely prescribed for presbyopia by ophthalmologists.”
(Edited by Radifah Kabir)
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