Lupin’s Karkaria On Biosimilars Pushback And Interchangeability
Questions Need For Separate Studies
Executive Summary
Lupin's biotech president notes push-back by innovator firms against biosimilars in the US parallels that witnessed when small molecule generic competition first emerged, but remains confident that biosimilars will gain traction. The executive also sees little need for separate interchangeability studies.
Innovator firms have deployed several tactics to derail uptake of biosimilars in the US, including whisper campaigns that allege such drugs are inferior to interchangeable products and their original reference drugs, and contracting that threatens the loss of rebates on other products if a biosimilar is placed on a formulary.
Cyrus Karkaria, president of Lupin Ltd.’s biotechnology division, notes however that such push-back is playing out along similar lines as those seen when small molecule generics first arrived several years ago and that firms need to adapt. He is confident that biosimilars will eventually "prevail", just as in the case of generics.
In an interview with Scrip, Karkaria recalled that he was in the US when the Hatch-Waxman Act was passed (in 1984) and how some innovator firms then spread “horror stories” on what was going to happen and questioned how “something [generics] which is so inferior” could be permitted.
“These things have been there since day one. The biosimilar story is a repeat of exactly what it used to be for generics. And the uptake [of generics] was bare minimum till the 90s, so it took a significant amount of time for the uptake to happen, where now it is almost 90%,” observed Karkaria, who has previously worked for Biogen.
Over four billion generic prescriptions were filled across the US in 2018, representing 90% of dispensed prescriptions, up from 75% in 2009, according to the Association for Accessible Medicines’ 2019 Generic Drug and Biosimilars Access & Savings data for the US.
Karkaria, who was also vice president of operations and biopharmaceutical process sciences at Celldex Therapeutics Inc. and CuraGen Corp. in the US prior to joining Lupin, expects similar tactics against biosimilars to persist, since innovator firms have a lot to lose. Revenues run into billions for some original biologics and face the risk of “running dry.”
“We will just have to adapt to different business scenarios. So far, we have prevailed in the generics market so I don’t see why we won’t prevail here [in biosimilars]. But there is lot of work to be done and the US Congress will have to do some legal maneuvering for it to actually be an even playing field,” Karkaria said.
Catching Up With Korean Firms
Lupin’s biotechnology chief emphasized the importance of high-quality manufacturing in the overall scheme of things for biosimilars and believes that India has a “big advantage” for cost-effectiveness. (Also see "Lupin's Gupta On Getting Biosimilar Manufacturing Right, Albuterol Outlook" - Generics Bulletin, 21 Jun, 2019.)
“Right now for developed markets the actual percent of discount is not that high, but come more competitors and that’s going to change,” Karkaria predicted.
While South Korean companies currently have a head start in the biosimilars sector, having invested much earlier in the space, Karkaria said that Indian firms are now playing catch up and believed that within a few years they could be at the same level “with the same or better quality and also cheaper.”
Interchangeability Studies
The executive appears unconvinced about the requirement for interchangeability studies for biosimilars in the US, adding to the growing list of industry executives who believe these studies essentially only pile up cost and bring few real benefits to manufacturers.
He explained that most of the time in the past, interchangeability was done for small molecules because “you just had BA/BE [bioavailability/bioequivalence] studies and you’ve never really seen efficacy” but in the case of biosimilar efficacy, this is already shown in trials.
“In short, your interchangeability is clearly verified [during clinical development]. You are comparing it [the biosimilar] with the RLD [reference listed drug],” Karakaria said.
But he didn’t want to go as far as saying that interchangeability studies are “absolutely not needed” because the US Food and Drug Administration still has "the impression that it’s needed. And the innovator companies will make damn sure that we go through the whole thing. So there is ambiguity,” Karkaria said.
Lupin’s own filing for biosimilar etanercept in the US, he added, was on track and the firm is progressing with bridging studies but not interchangeability because it wasn’t clear “exactly what is needed as yet.”
“Even our competitors haven’t done it [interchangeability] so it doesn’t seem like it’s really necessary so far.”
The Lupin executive's views are generally in sync with recent comments by some other executives of Sandoz Inc., Mylan NV and Samsung Bioepis Co. Ltd., who believe that US interchangeability studies may not be worthwhile; the trials are also expensive and patients difficult to recruit.
The concept of interchangeability has led to confusion and uncertainty and also fuels the mis-perception that non-interchangeable biosimilars are inferior, experts said at an Association for Accessible Medicines' generics and biosimilars conference (see sidebar).
‘No Need For Separate Studies’
Karkaria, however, appeared enthused about the general scenario around interchangeability of biosimilars in Europe, where some countries have taken encouraging steps.
"There are quite a few caveats in different countries…but France, Scandinavia, Germany have openly said there is no reason why not. Some other countries are a little bit more nuanced."
France is said to have developed legislation to introduce financial incentives for hospitals to favor biosimilars and Germany is reported to be looking at pharmacy-level automatic substitution of biologics from 2022. (Also see "German Doctors Fear ‘Nocebo’ Impact From Substitution" - Generics Bulletin, 16 Sep, 2019.) (Also see "France trials range of biosimilar incentives" - Generics Bulletin, 14 Sep, 2018.)
Karkaria underscored that “all in all” there is no need for separate studies. “It’s just basically delaying things and costing much more…that’s basically coming up from the payers because when the company has to spend so much, there’s only so much discount you can give before it makes any business sense,” he explained.
He also sought to dismiss innovator firm tactics suggesting that biosimilars are inferior to interchangeable products and their reference products, referring both to the NOR-SWITCH study that demonstrated no adverse impact from switching to biosimilar infliximab and those for Lupin’s own biosimilar etanercept.
“For our etanercept product, our trials clearly state that our safety parameters are much better than the safety parameters of the innovator. That doesn’t mean that the innovator [product] is not safe - it’s just that from what they [innovators] are stating that biosimilars are inferior, that’s not the case at all,” he emphasized. (Also see "Pfizer Wants FDA To Stop Sponsor Promos From Implying Biosimilars Are Inferior" - Pink Sheet, 28 Aug, 2018.)
Lupin had earlier inked a deal with Mylan under which the US firm will commercialize Lupin’s biosimilar etanercept in Europe, Australia, New Zealand, Latin America, Africa and most markets throughout Asia. A launch in Europe is expected in the next financial year. (Also see "Mylan Pursues ‘Market First’ Playbook, Partners Lupin For Enbrel Biosimilar" - Scrip, 29 Jun, 2018.)
US studies for Lupin’s biosimilar pegfilgrastim are also ongoing and Karkaria said the firm isn’t deterred by the head start competitors Coherus BioSciences Inc. and Mylan have.
“We are pretty resolute on promoting it and launching it ourselves currently. Our projections are pretty modest at this stage so for what we have, we should be fine still,” he predicted, underscoring the huge US market opportunity for the product, which means there is “plenty of room for a lot of players.”