Do all roads eventually lead to interchangeability?

So…it happened…Donald J Trump has been inaugurated as the 45th President of the United States of America. Those who know me will confirm that I predicted it. When the British people voted for Brexit, I sensed a change in the air. The unexpected and impossible suddenly became the expected and possible. In the UK and US, people have voted for change. Congratulations, Mr Trump…sorry, Mr President! Let’s see where this takes us.

In other news, the FDA published its much-vaunted interchangeable biosimilar guideline. First, congratulations to the FDA for publishing it!

I’ve gone on record and said that there’s nothing in the guideline that leaps out as me as being unreasonable or unexpected. I’m sticking to that, and industry experts have agreed with me.

Some might think that asking for studies against US-sourced reference product makes no scientific sense (and I’d agree to a point). I see this as a practically focused decision. US patients are only ever going to be switched from a US approved reference product, so why allow non-US approved reference product to be used in switching studies? It might make no scientific sense, but I’d appreciate your comments on this.

In terms of the studies that the FDA has asked for, no surprises here either. We need to remember that companies, like Coherus and Momenta, are already doing studies with their respective adalimumab biosimilars per the proposed “integrated study design.” Companies don’t do things in the vein hope that the regulators will agree. The FDA has given scientific advice on these studies. Or did Coherus and Momenta just get lucky?

The guideline also got me thinking on the longer-term relevance of interchangeability. Sure, for some products in the early stages of their commercial life, being interchangeable could be beneficial to some products (e.g. self-injected products, like the anti-TNFs) for some companies (i.e. smaller companies with limited sales and marketing muscle). It could help the product gain traction, drive real world experience.

Longer-term, all biosimilars will be deemed interchangeable with the reference product by payers, even if the FDA doesn’t approve them as such. In some classes the issue of product interchangeability doesn’t even factor into thinking, such is the rapid churn of patients (e.g. filgrastim use in preventing CINV). It’s relevance in the infused product setting is also questionable.

Outside of the US we’re already seeing non-medical switching (or therapeutic substitution, whatever you want to call it). How do you think infliximab biosimilars have done so well in the Nordics? I see this happening in the US as well. Excluding brands in favour of biosimilars, like what Express Scripts and CVS have done with Neupogen and Lantus, will become the norm when the price is right. What was once considered impossible now seems more likely.

On the regulatory front, we’ve seen some more submissions at the EMA and FDA. There have been two bevacizumab biosimilars submitted to the EMA (both are from Amgen/Allergan, per my sources), and another adalimumab biosimilar submission accepted by the FDA and EMA this week.

Congratulations to the team at Boehringer Ingelheim on BI 695501, its proposed adalimumab biosimilar, being accepted for review in Europe and the US; a great achievement. There are currently four adalimumab biosimilars on the CHMP’s January 2017 list of products under review, so have we uncovered who’s behind the “ghost” adalimumab submission I’ve talked about on Twitter?

With Amgen’s ABP 501 (which is behind two, per my source) and Samsung’s SB5 confirmed, and FKB’s FKB327 believed to be behind another (if it’s not, please get in touch, but this is the feedback I’ve been getting), is Boehringer’s BI 695501 the 5th adalimumab biosimilar. I guess we find out in February when the CHMP updates is list of medicines under review.

Finally, a hugely significant court case started in the UK this week. Following a ruling by Justice Henry Carr in December 2016, and a subsequent ruling in early January 2017, FKB and Samsung Bioepis have been given the opportunity to obtain an Arrow declaration which will prevent AbbVie from suing FKB and Samsung in relation to their adalimumab biosimilars. I’m not a lawyer, so I won’t embarrass myself and try and explain the details of the case. Suffice to say, this case has huge implications for adalimumab biosimilars, not just in the UK but across Europe.

Take care peeps, enjoy your weekends!

Duncan (aka @biosimilarz).

Baby steps back to blogging…please be gentle!

As many of you know I took the decision early last year to stop blogging. My reasons for doing this were manifold, and I’m not about to bore you with the details (although some of you know some of the reasons). The messages I received from people asking me to start blogging again, how much people enjoyed my posts and the support some of you gave me last year during some difficult times were amazing. All I can say is thank you.

So today I’ve decided to get back into blogging. About biosimilars, but about a lot of other things as well. Don’t be surprised if you see me comment on a wide range of things this year, like movies, music, sport, politics, the latest Star Wars Lego toy that I’ve purchased (I’m working my way through this list of key rings at the moment; R2D2 is next up on my list), general pharma issues. And of course, biosimilars.

All of this being said, it’s important to lay down some rules of the road, so I can manage people’s expectations. I’ll only be blogging at the weekends, days off and public holidays. I have a job and my employers deserve nothing else than my full attention during the working week. Some of the bells and whistles I used to provide before have gone and won’t return. Things like lists, the Wall of Shame, that kind of thing. This blog will now be 100% my personal opinion on things. Quickfire blogging will become the norm. Perhaps most importantly, my blog is meant to be fun. I want to look forward to blogging, not see it as a chore. It’s not to be take too seriously. And it must never be used against me!

On the subject of biosimilars, 2017 is looking like it could be another bumper year for the biosimilars market. Lots of other people have said as much, and for the most part I agree. Plenty of news flow is expected in terms of clinical data, regulatory approvals, launches, more colour on how the commercialisation of biosimilars is going to look, and how lawyers will continue to get rich on both sides of the Atlantic.

I’ll be dipping into some of the key events from the last 12 months, and giving you a view on what to look out for over the next 12 months, very soon. After all, 2017 is only two weeks old. That being said, I can’t wait for the next Star Wars movie, and the Bladerunner sequel (Bladerunner 2049) looks frickin’ awesome.

Take care peeps, enjoy your weekends!

Duncan (aka @biosimilarz).


Biosimilars; why words matter…

I’ve never been a huge fan of dumbing things down. Letting things slide when the right thing to do is to correct something. Take my approach to parenting. Sometimes the easiest thing to do, while talking to my kids at the dinner table, is to not correct their verbal mistakes. In ones so young, mistakes in the correct use of language are inevitable. But to let things slide, to not correct them, is bad parenting.

We’ve reached a point in the biosimilars market where we’re all sitting at the proverbial “dinner table.” Talking about how the market could play out. Where it’s headed. And what challenges still remain (of which there are many). It’s a busy table. Everyone wants to have their say. To take center stage. It’s an exciting place to be. But sometimes people use language that, in my opinion, needs to be corrected.

Take the words “knock off” and “copycat”. These two words, phrases, clichés, whatever, you want to call them, have become media bywords for biosimilars. Both words are associated with counterfeit, sub-standard products. Like handbags, sunglasses and watches. It’s a huge shame that this has happened. And I’d like to give my two cents worth on why.

Biosimilars have been used in Europe since 2006, when Omnitrope (a somatropin biosimilar) from Sandoz was approved and launched. Since then we’ve had over 20+ other biosimilars approved and launched in Europe, the US, Japan and other highly regulated markets. According to Medicines for Europe, EU-approved biosimilar medicines have generated more than 400 million patient days of clinical experience worldwide. And the number of safety issues? None. The number of product recalls? None.

Biosimilars are high quality, safe and effective products. They meet stringent regulatory requirements in many countries around the world. And even in markets which have been associated with lower regulatory standards for biosimilars in the past, there are signs that standards are improving. To call them “knockoffs” or “copycats” is disingenuous.

But I can understand why these words are used. It’s easier than trying to explain the science behind biosimilars. I get that. But I’m still not a fan. It just doesn’t sit well with me. It gives the wrong impression to people who don’t understand the space. Like parenting, we have a responsibility to teach those that don’t understand something. As for what synonym is best to describe a biosimilar without resorting to “knockoff” or “copycat”? I’m still pondering on that, and I welcome your suggestions…

| 07.12.2014 | An interview with Don Stewart; President, CEO, and founder of PlantForm Corporation…

An early defense strategy used against biosimilar developers by the originator biologics industry was a firm focus on the “process is the product” paradigm. Early presentations from the European Medicines Agency (EMA) put forward the concept of “one process – one product”, suggesting biotechnological medicinal products are “individuals”. Moreover, companies such as Roche still maintain on their websites that “how” a product is made significantly impacts “what” product is made, and governs product quality and similarity compared to the reference product.

Flying in the face of this perceived wisdom, companies were set up to exploit advances in plant cell biotechnology (e.g. PlantForm, SemBioSys), humanised yeast (e.g. GlycoFi), and transgenic animals (e.g. Pharming, GTC Biotherapeutics) in a move to develop cheap and facile platform technologies that could provide an alternative to expensive mammalian cell production processes. While many of the companies mentioned previously have either folded or have been acquired by large pharma players, Canadian biotech, PlantForm Corporation, remains independent and is moving forward with its strategy of developing low-cost biologics manufactured using plant cells.

Advances in plant cell biology have provided PlantForm with an opportunity to make high quality biologics at a fraction of the price compared to traditional, mammalian cell processes. In an exclusive interview, Don Stewart, President & Chief Executive Officer, and founder of PlantForm, talks to The Biosimilarz Blog about the company’s history, its pipeline, strategy, how it intends to differentiate itself from other biosimilar players, its aspirations for the future and how he sees the wider biosimilars market evolving over the next few years.

PlantForm was established in 2008, having licensed its plant cell technology from the University of Guelph, where it was developed by Dr J Christopher Hall, the Canada Research Chair in Recombinant Antibody Technology. Key to the technology was its ability to make the plant cells more “mammalian-like.” As Stewart points out; “We have tobacco plants that have been engineered to produce proteins similar to those produced by mammalian cell culture. All of the correct glycosylation machinery has been engineered into the plant cells, and anything that’s not needed has been removed. By doing this we can ensure that all of the therapeutic proteins produced using our technology are as ‘mammalian-like’ as possible.”

PlantForm’s technology platform is capable of producing a wide range of biopharmaceutical products, including monoclonal antibodies (mAbs), therapeutic proteins and vaccines. The company’s lead product is a proposed biosimilar version of Roche’s Herceptin (trastuzumab), which generated global sales of $6.8 billion in 2013. Data published in 2010 showed that the company’s proposed biosimilar version of trastuzumab inhibited the growth of HER2 positive cancer cells. Then in 2012 more data was generated, this time an in vivo study in mice, showing that the company’s proposed biosimilar version of trastuzumab was as effective as Herceptin in reducing the size of breast cancer tumours.

Based on this data, Stewart is excited about the future; “We’ve generated some exciting data so far, and plan on completing all pre-clinical work on the [potential] biosimilar trastuzumab candidate by the end of 2015. Phase I clinical trials are scheduled to start in Q1 2015 and should be completed 12-18 months after that.” And while biosimilars are a key focus for the company, Stewart was keen to emphasise that PlantForm is more than just a biosimilar developer; “PlantForm has a definite focus on biosimilars, but we’re more than just a biosimilars company. We’re also developing novel mAbs for the treatment of HIV, and we’ve worked with DARPA [Defense Advanced Research Projects Agency] in the US to develop an anti-biological warfare agent. There are also several other, longer-term opportunities that we’re looking into.”

In many ways, PlantForm is a little late to the game when it comes to developing biosimilar versions of trastuzumab. Companies such as Celltrion, Amgen, Pfizer and Samsung Bioepsis are all in Phase III clinical testing for their respective candidates. But Stewart remains unfazed by this due to a clear company strategy that seeks to play to the company’s strengths; “We acknowledge that we’re behind other companies when it comes to the development of biosimilar trastuzumab. Critical to our strategy are the emerging markets. These markets form the foundation of everything we want to achieve at PlantForm, and getting it right in these markets will allow us to move into the developed markets of Europe and the US.” Stewart continued by emphasising the key benefits of the manufacturing technology; “Our technology platform provides several advantages over mammalian cell culture, which is being used by all other biosimilar developers. It’s fast, efficient, highly versatile and easily scalable. Best of all, it’s capable of reducing manufacturing costs by up to 90 per cent.”

The attraction of PlantForm’s manufacturing technology was key to a recently announced joint venture (JV) that it has established with Brazil’s PharmaPraxis. The JV will target 6 different drug candidates, with the initial focus on a biosimilar/biobetter version of Roche’s bevacizumab (Avastin), which generated global sales of $7 billion in 2013. As Stewart explained; “We’re very excited by the deal with PharmaPraxis as it validates our technology and allows us to move forward with our strategy.”

The sustainability of the biosimilars market remains a key area of debate, with limited consensus existing as to the market’s evolution. Due to the ever-increasing costs of healthcare, Stewart remains bullish about the future of the biosimilars market, saying that in order to be able to deliver high quality care in the future, the biosimilars market has to succeed; “The costs of healthcare are not coming down, so governments and payers are all looking at ways of saving money. High quality biosimilar products can provide part of the solution, and this is one of the reasons I remain optimistic about the future of the biosimilars market.”

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