A second complete response letter for a Rituxan biosimilar in as many months illustrates how the US remains tough for those hoping to launch cheap versions of biological drugs. Sandoz’s rejection yesterday came after Celltrion was knocked back in April.
Make no mistake – these sorts of events are becoming much more relevant to the traditional pharma groups that have moved into this space. Pfizer’s Rituxan biosimilar is ranked as its most valuable R&D asset, while Amgen’s rival project is considered its second most important, and both companies have much riding on their biosimilar pipelines (see analyses below).
That Pfizer counts four biosimilars among its five most valuable R&D projects is astonishing, and arguably reflects a failure of the company’s novel research efforts as much any fundamental strategic shift.
As a biotech company Amgen’s move into this space is more understandable. Amgen has already won approval for its Humira biosimilar, and its Herceptin biosimilar Kanjinti is due an FDA decision by May 28.
|How biosimilars dominate: the five most valuable R&D projects among Rituxan biosimilar players|
|Today's NPV ($bn)|
|ABP 798 (Rituxan biosimilar)||2.73|
|Kanjinti (Herceptin biosimilar)||1.90|
|ABP 710 (Remicade biosimilar)||1.07|
|Total NPV of R&D pipeline||12.39|
|Biosimilar NPV's as proportion of total||48%|
|PF-05280586 (Rituxan biosimilar)||3.09|
|PF-05280014 (Herceptin biosimilar)||2.82|
|PF-06439535 (Avastin biosimilar)||2.82|
|PF-06410293 (Humira biosimilar)||1.78|
|Total NPV of R&D pipeline||18.86|
|Biosimilar NPV's as proportion of total||56%|
|Herzuma (Herceptin biosimilar)||0.73|
|Truxima (Rituxan biosimilar)||0.59|
|Teriparatide Recombinant Human (Forteo biosimilar)||0.23|
|Total NPV of R&D pipeline||4.69|
|Biosimilar NPV's as proportion of total||33%|
Rituxan is a huge target for biosimilar developers, having generated $4.2bn in US sales for Roche last year. The Swiss company was no doubt delighted with the news from Sandoz, Novartis’s generics arm, yesterday; analysts believe that the cancer antibody could remain uncontested in the US until next year.
Pfizer and Amgen are further behind with their rituximab projects. Pfizer reported positive phase III data from the Reflections B3281006 study in January, but has to yet to file for approval in any region. Last month its Herceptin biosimilar received a complete response letter, highlighting how these programmes seem prone to hitches.
Celltrion’s manufacturing problems are well known, so the complete response letter from the FDA for both its rituximab and trastuzumab (Herceptin) biosimilars did not come as a huge surprise. The company, which is partnered with Teva on these assets in the US, insists it can still win approvals this year; the South Korean firm is no doubt under considerable pressure from the beleaguered Israeli generics giant to solve these issues.
The story is different in Europe, where Celltrion has been able to dominate the market largely thanks to Sandoz's supply problems. Uptake of rituximab biosimilars has been very fast in the region – research by Bernstein analysts estimates that Celltrion and Sandoz grabbled 28% of the market with their products within the first 12 months. Roche could have lost half the European Rituxan market by the end of 2018, Bernstein estimates – with Celltrion being the clear winner.
The slow uptake of biosimilars that have been launched in the US – best illustrated by Pfizer’s struggles to grab a share of Remicade’s market – suggests that Rituxan knock-offs are unlikely to replicate their strong start in Europe across the pond.
The path to commercial success in the US has already proved to be far tougher to navigate than in Europe. But, as this analysis shows, companies like Pfizer and Amgen have a huge vested interested in changing this, even as they defend parts of their own portfolio against similar incursions.
|Rituxan biosimilars – the main players|
|Global sales ($m)|
|Company||Product||US status (projected launch date)||EU status (projected launch date)||2020e||2024e|
|Celltrion/Teva||Truxima||CRL April 2018||Launched April 2017||458||561|
|Pfizer||PF-05280586||Phase III (end 2019)||Phase III (end 2019)||163||458|
|Amgen||ABP 798||Phase III (end 2019)||Phase III (end 2018)||178||478|
|Novartis (Sandoz)||Rixathon||CRL May 2018||Launched June 2017 (had supply issues)||not available||not available|