Posted 06 September 2017
By Zachary Brennan
The US Food and Drug Administration (FDA) on Wednesday released a Form 483 sent to Korea’s Celltrion with 12 observations, which an industry analyst believes could be the reason why the commercialization of Celltrion and Pfizer’s Inflectra (infliximab-dyyb), a biosimilar to Remicade, has not gone as well as planned in the US, though Pfizer says the limited uptake has more to do with Johnson and Johnson's exclusionary contracts.
The Form 483 for the Incheon, Korea-based manufacturing site, following an inspection last May and June, includes several repeat observations, including the site’s failure "to demonstrate that your manufacturing process can reproducibly manufacture drug substance meeting its predetermined quality attributes."
FDA inspectors also found that the source of particles detected in a visual inspection "has not been identified," and there was mold on some of the facility’s walls.
In a note to investors on Monday, Bernstein biotech analyst Ronny Gal said one of the critical observations "refers to problems with the vial stopper and states FDA received 140 complaints (presumably from physicians) about the stopper. The letter is redacted, so exact problem is unclear."
Gal also contends that the stopper problem is an additional explanation for why Celltrion’s partner Pfizer "did not push Inflectra more broadly. Now with competitor Bioepis/Merck launching [the second Remicade biosimilar was approved in April], the latter has an advantage (Merck presumably would not be shy about sharing the 483 with potential clients)."
Other problems, he said, "should be solvable" though the observations suggest Celltrion "ran into a solid inspector who picks on stuff like how they label equipment and validating the cleaning supply for washing the walls (as well as more material stuff like computer record)… However, the inspector did not suggest that (i) Celltrion has intentionally hid stuff from FDA, although there some 'unofficial' documentation and testing which FDA hates; (ii) bad product is released or could be released, (iii) there are ‘structural’ problems with the facility or culture (e.g. poor airflow/ fundamental misunderstanding of requirements)."
For the first quarter of 2017, Pfizer reported Inflectra and Remsima, which is the name of the Remicade biosimilar in the EU, sales as $78 million, which is more than double what the company reported in the same quarter in 2016, but also shows the company has not yet nabbed a large share of the market from the brand name product.
Gal noted recently that the Inflectra's "very modest market inroads" may also be due to an effective strategy from Johnson & Johnson.
A Pfizer spokesman told Focus: "Inflectra uptake in the US is
being limited due to exclusionary contracting of originator companies with
insurers and providers. In the commercial insurance space our lower-priced
Inflectra has not received access at parity to Remicade and remains in a
disadvantaged position despite recent price increases taken by J&J. This is
in contrast to Medicare, where biosimilar coverage has been strong."
Although as prices come down with more Remicade biosimilar competition, the share of biosimilars may continue to increase.
Pfizer noted Inflectra’s list price (Wholesale Acquisition Cost (WAC)) is $946.28 per 100mg vial which is 19% lower than the current wholesale acquisition cost (WAC) for Remicade. The list price is not inclusive of price discounts, rebates and other factors. And beginning 1 October, Inflectra’s Average Selling Price (ASP) will be $737.91 per 100mg vial vs. Remicade’s ASP of $822.96.
Updated with comment from Pfizer and updated prices for Inflectra.