Celgene is one of only two major drug companies to make a big commitment to CAR-T, and its executives speak bullishly of the space. Then again they would do, since they have a huge investment to justify: a 10-year collaboration with Juno that cost $1bn up front.
In the next couple of years the US biotech will look to put more money where its mouth is, as decisions on manufacturing investments approach. “At the very start… we said we wanted to see at least two truly breakthrough therapies come out of this collaboration,” George Golumbeski, head of business development and alliance management, told EP Vantage, adding that these would likely come from solid tumour targets beyond the low-hanging fruit of the CD19 antigen.
It is the anti-CD19 CAR-T assets that are the most advanced in Juno's pipeline; the group expects data later this year from the Rocket trial of JCAR015 in adults with acute lymphocytic leukaemia that could form the basis of US approval. Celgene bought ex-US and China rights to this and Juno's other CD19 targeting programmes last week.
Mr Golumbeski said the CD19 option would likely be the first of many steps forward with the collaboration, which was only forged last June (Celgene goes for broke, June 30, 2015).
“As excited as we are about the option, this is a CD19 construct; there are competing constructs, and it’s going into B-cell disease where we have a lot of good medical treatments," he said. "Our aspiration is to see this collaboration produce drugs that can be dramatically effective and possibly curative in certain tumour states where there are no good treatments, including solid tumours."
And he made no secret of just how ambitious Celgene is: "If one of these therapies starts to work in glioblastoma or pancreatic cancer, for example, I think the authorities and industry will band together to make them available. If you get enough specificity built into your targeting moiety you could have great efficacy in solid tumours."
Still, actual results supporting strong CAR-T activity in solid cancers have been conspicuous by their absence. Many believe that this technology is a long way from generating the robust clinical data even to begin to know whether these sorts of achievements are possible.
And, even then, figuring out how and where to manufacture these complex autologous therapies is still going to present a major problem (Adopt Summit – Manufacturing is still the biggest hurdle for CAR-T, March 7, 2016).
“Juno is making significant steps and has invested heavily in turning this into a truly robust and scalable process, and that ultimately will be a big advantage for us and for them,” said Rupert Vessey, Celgene's president of research and early development. “If you look at the competing organisations they are really just in proof of concept mode, in terms of delivery, maybe just good enough for a small trial.”
Mr Vessey and Mr Golumbeski were speaking to EP Vantage at an event at Celgene’s European headquarters in Boudry, Switzerland, to mark 10 years on the continent for the company. The two topics chosen for discussion – the promise and reality of curing disease and the economics of health – could not be more pertinent for the CAR-T space.
For while the technology promises huge steps forward clinically, if this comes to pass the cost will likely be equally ground-breaking.
Companies like Celgene, which are prepared to invest in these huge steps forward in medical treatments, have to believe that the money will be found to pay for such therapies should their aspirations become reality. And great emphasis was placed at the event by many of the company’s executives on the need for greater collaboration between payers, patients and industry, to improve access to innovative treatments.
“We need a framework for assessing value that we can all agree on,” Jackie Fouse, Celgene’s chief operating officer, said during a panel discussion.
Pulling the trigger
Celgene will soon have to make decisions about building its own manufacturing capacity, though what this will look like is far from determined.
“We will be manufacturing in Europe,” Mr Golumbeski said. “But it’s not clear at the moment how many patients will need to be treated, or depending on international laws whether we will need one or many facilities.” Since CAR-T therapies might make it to market next year, as their developers hope, the fact that such fundamental decisions are still up in the air will come as a surprise.
Speaking to EP Vantage Celgene’s newly appointed chief executive, Mark Alles, made similar comments. In Europe, where there are a number of regional regulators, it seems that it has yet to be determined whether a central manufacturing site will suffice.
CAR-T manufacturing “would need geographical flexibility. We are looking globally for logical places,” Mr Alles said, adding that “the question is ‘will we have to?’ rather than ‘do we want to?’.”
The size and scope of the Juno deal reveals a belief in a field in its infancy that could develop in many directions; the company also has a CAR-T collaboration with Bluebird Bio, but this was scaled back before the Juno deal to focus on just one asset targeting BCMA.
Evidence to trigger Celgene's investment in manufacturing, and to begin to justify its monster investment, is within a “single-digit year type of time frame. It’s not a decade away,” said Mr Vessey. Success will not come cheap, but at least Celgene is well positioned to benefit as and when breakthroughs in this space emerge.