SAN FRANCISCO — After some tweaks to the manufacturing process, Razumab (Intas Pharmaceuticals), a biosimilar designed to mimic ranibizumab (Lucentis, Genentech), appears to be safe and effective, new research shows.
Although the high incidence of inflammation associated with the first three batches seems to have been resolved, "there are issues with the manufacturing process of biosimilar drugs, particularly the stability of the drug from batch to batch and the immunogenicity analysis," said Alay Banker, MD, from the Bankers Retina Clinic and Laser Centre in Ahmedabad, India.
Dr Banker presented data on a case series of patients undergoing treatment with Razumab here at the American Society of Retina Specialists 2016 Annual Meeting.
Biosimilars are biologic products designed to replicate the molecular structure of existing biologic therapies. Like generic drugs, they generally cost much less than the biologics on which they are based.
Razumab is one of several biosimilars being developed around the world to compete with the antivascular endothelial growth-factor treatments of ranibizumab, bevacizumab (Avastin, Genentech), and aflibercept (Eylea, Regeneron Pharmaceuticals).
To date, the US Food and Drug Administration has not approved any biosimilars for use in ophthalmic medicine.
In a randomized head-to-head comparison of ranibizumab and its biosimilar, effects on best corrected visual acuity and central retinal thickness were statistically equivalent, and the biosimilar was approved by the Drugs Controller General of India in June 2015.
In India, a 10 mg/mL dose of the biosimilar sells for the equivalent of US$240; the same dose of ranibizumab sells for the equivalent of US$340.
A brief ban on the use of bevacizumab in India stimulated widespread use of Razumab, and 4668 injections were administered from July 2015 to July 2016.
However, about 10% of patients who received product from the first three batches of the biosimilar experienced inflammation, Dr Banker reported, although all were successfully treated with steroids. "The main problem with biosimilars is the stability and batch-to-batch maintenance of the standard of the drug," he explained.
In response to the problem, Intas introduced an additional filtration step to its manufacturing process and added fresh "ultrapure Polysorbate 20." From batch 4 onward, no such adverse events have been reported, said Dr Banker.
In Dr Banker's clinic, 174 injections have been administered to 94 eyes — 26 with choroidal neovascularization, 43 with diabetic macular edema, 13 with retinal vein occlusion, and 12 with retinopathy of prematurity.
At a mean follow-up of 15.3 weeks, there was a significant improvement in average logMAR visual acuity, from 0.53 to 0.37 (P < 0.05), and a significant decrease in mean central retinal thickness, from 359.65 to 298.68 µm (P < .01).
Resolution of threshold disease was achieved in eyes with retinopathy of prematurity.
No abnormalities were found on electroretinography, and there were no significant adverse events.
"In our short-term study of a very small size — 94 eyes — we suggest that this new biosimilar, Razumab, is safe and effective for retinal vascular diseases, although long-term data and immunogenicity studies are still required," he concluded.
He pointed out that a phase 4 study of the treatment is underway.
A second study of Razumab was presented at the meeting by Shrinivas Joshi, from the Joshi Eye Institute in Hubli, India.
He reported data on 123 eyes — 44 with diabetic macular edema, 46 with choroidal neovascular membranes, and 33 with retinal vein occlusion. All the eyes had gained visual acuity at 1 month, but the change was significant only in eyes with retinal vein occlusion and in the entire series.
Table. Change in Best Corrected Visual Acuity (LogMAR)
|Eyes||Baseline||1 Month||P Value|
|Diabetic macular edema||0.6||0.5||0.198|
|Choroidal neovascular membrane||0.8||0.6||0.118|
|Retinal vein occlusion||0.9||0.6||0.005|
Dr Joshi said he agrees with Dr Banker that the treatment could become a "safe, low-cost therapy for macular diseases in developing countries."
Dr Banker noted that Intas has applied to conduct phase 3 trials with an aim to gain approval for the biosimilar when the patent for ranibizumab expires in the United States in 2020 and in Europe in 2022.
In the meantime, Indian companies have launched two bevacizumab biosimilars: Cizumab by Hetero; and Bevacirel by Reliance Life Sciences.
But the treatment might not find a ready market in the United States, said Timothy Murray, MD, from Murray Ocular Oncology and Retina in Miami, who served as session moderator for Dr Joshi's presentation.
First, Genentech would probably lower the price of ranibizumab to compete, he told Medscape Medical News. And second, physicians in the United States might be willing to pay more for ranibizumab than for the biosimilar because of worries about problems such as the adverse events reported in India.
"I think there is a lot of potential risk in the way these drugs are manufactured," he said. "We would pay a premium for the peace of mind."
But some payers might only be willing to reimburse for the cost of the biosimilar, in the same way they sometimes only pay for the cost of generic drugs, forcing patients who want brand-name drugs to pay the difference.
He said he is struck by the much lower cost of ranibizumab in India. In the United States, it sells for about $2000 per dose, he pointed out.
Dr Banker reports that he has received honoraria from Novartis and Santen. Dr Joshi has disclosed no relevant financial relationships. Dr Murray reports that he is a consultant for Alcon and has received research support from Regeneron.
American Society of Retina Specialists (ASRS) 2016 Annual Meeting. Presented August 13, 2016.
Medscape Medical News © 2016 WebMD, LLC
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Cite this: New Batches of Ranibizumab Biosimilar Safe, Effective - Medscape - Aug 15, 2016.