Biosimilars Reported Safe, Effective for Retinal Disease

Laird Harrison

October 29, 2018

CHICAGO — Biosimilars made in India are as safe and effective for retinal vascular diseases as the American-made originator drugs, but cost about 40% less, according to a comparative analysis.

"Biosimilars could become the future for biotherapy in retinal diseases," said Alay Banker, MD, from Bankers Retina Clinic and Laser Centre in Ahmedabad, India.

He presented a chemical, clinical, and economic comparison of ranibizumab (Lucentis, Genentech) and its biosimilar Razumab (Intas) and bevacizumab (Avastin, Genentech) and its biosimilar ZyBev (Cadila Healthcare) here at the American Academy of Ophthalmology 2018 Annual Meeting.

Banker's patients have benefited from thousands of injections with the biosimilars for choroidal neovascularization, retinal vein occlusion, and diabetic macular edema, he reported, with few adverse events.

Like generic drugs, biosimilars are designed to replicate the original drugs after patents expire. But because biosimilars are chemically synthesized to mimic biologics, which are manufactured in a living system, molecular structures of the two products can be slightly different.

A previous mass spectrometry analysis, supported by Novartis, showed that although the molecules of ranibizumab and Razumab are not identical, key properties are very close (MAbs. 2017;9:1337-1348), Banker explained.

The cell-based functional potency for binding to VEGF of Razumab is 99% to 100% of that for ranibizumab. And there is no difference in the inhibition of VEGF-induced proliferation between the two molecules.

"Even the analysis of the size and charge variance by the separation techniques is very similar between the two molecules," Banker said.

The patents for ranibizumab and bevacizumab expire in 2020 in the United States, opening up potentially lucrative markets for biosimilars.

Razumab, approved for sale in India in 2015, sells there for US$190 per vial; ZyBev, approved in 2017, sells there for US$190 per vial.

So far, 52,000 vials of Razumab have been used. With the first three batches, about 10% of patients experienced inflammation, but that was successfully controlled with steroids, Banker explained during a presentation at the American Society of Retina Specialists 2016 Annual Meeting, as reported by Medscape Medical News.

"The main problem with biosimilars is the stability and the batch-to-batch maintenance of the standard of the drug," he said at the time.

To address the problem, Intas introduced a filtration step to its manufacturing process and now adds fresh ultra-pure polysorbate 20.

Banker's follow-up of 1545 injections of Razumab and 2237 injections of ZyBev showed that visual acuity improved, on average, for choroidal neovascularization, retinal vein occlusion, and diabetic macular edema.

Intraocular inflammation occurred in 14 of the eyes treated with Razumab and eight of the eyes treated with ZyBev, but none of the patients experienced any systemic issues.

Table 1. Razumab Outcomes
Outcomes Baseline 2 Years P Value
Visual acuity, LogMAR 0.72 0.54 <.5
Central macular thickness, µm 406.15 314.10 <.01

 

Table 2. ZyBev Outcomes
  Baseline 6 Months P Value
Visual acuity, LogMAR 0.68 0.54 <.5

A Question of Cost

Banker presented a comparison of the cost of Razumab and ranibizumab in India done by Lalit Verma, MD, an ophthalmologist in New Delhi.

Verma determined that the total annual cost of treatment — cost to the doctor, cost to the patient, consultation costs, and imaging costs — was $2700 to $3700 for ranibizumab and $1600 to $1900 for Razumab, a savings of 40%, Banker reported.

"In the Western world, I don't think the price of biosimilars is expected to be anything like what you propose," said session panelist Baruch Kuppermann, MD, PhD, from the University of California, Irvine. "The 40% reduction may be achievable, but the hope that biosimilars will dramatically drop the price is probably not founded."

The market is different in India; insurance companies in India do not reimburse for VEGF inhibitors, Banker explained. And there are no compounding pharmacies. As a result, "we have had a lot of issues with Avastin. We had spurious drugs on the market causing a large epidemic of endophthalmitis."

Because of these safety concerns, many retina specialists are likely to switch to Razumab for their patients who can't afford the brand-name drugs, he said. "It's going to be a huge shift in how we treat our patients."

Multiple companies have formulated VEGF inhibitor biosimilars and are poised to sell them in the United States once patents expire, Banker added.

Banker has disclosed no relevant financial relationships.

American Academy of Ophthalmology (AAO) 2018 Annual Meeting. Presented October 26, 2018.

Follow Medscape on Twitter @Medscape and Laird Harrison @LairdH

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