In 2014, Bristol-Myers Squibb (BMS) and The University of Texas MD Anderson Cancer Center announced a pioneering research collaboration. They would evaluate multiple immunotherapy drugs as potential leukaemia treatments, running a number of studies in tandem.
This collaboration was notable for several reasons. Firstly, it dispensed with the usual one-drug, one-cancer approach to clinical trials by testing several drugs (in mono and combination regimens) at the same time. Secondly, it didn’t involve a contract research organisation (CRO), but brought academia and industry directly together.
“Collaborations between industry and academia can offer a faster and broader spectrum of clinical trials to benefit patients,” said Dr Hagop Kantarjian, professor and chair of MD Anderson’s Department of leukaemia, as the partnership got under way. “We hope innovative collaborations such as this can help lead to a higher likelihood for success across the board and will speed up the clinical development of new compounds for delivery to the patients who need them.”
Evolving research
Since then, the partnership has reaped impressive results. It has already led to a new standard of care for chronic myeloid leukaemia (CML) by optimising the dosage of dasatinib to make the therapy more effective and less toxic. As patients typically take this treatment on a long-term basis, any reduction in side effects will have a major impact on their quality of life.
On top of this, the research model has proved to be highly effective. BMS and MD Anderson are now applying it elsewhere; the former is working with other academic institutions and the centre with different pharma companies. According to Ferran Prat, senior vicepresident of research administration and industry ventures at MD Anderson, strategic alliances of this kind have clear benefits for all involved.
“We are not smart enough alone and nor are the pharmaceutical companies – we have complementary skills,” he explains. “Everybody knows and accepts that, yet the business framework we were using till now didn’t reflect that.”
Together with Kantarjian, the primary author, and several others, Prat recently produced a paper assessing their alternative research model. In May, the document was published in the American Cancer Society’s journal, Cancer, running through the ways research into the group of diseases has evolved over time and explaining why today’s standard methodologies are not necessarily the best option.
Removing the middleman
For background, recent decades have seen a strong shift towards pharmaceutical outsourcing, with pharma companies contracting more of their workload to CROs. This enables them to tighten their focus on late-phase drug development and marketing, while giving them access to resources and skills they may not have in-house.
However, according to the MD Anderson team, this methodology can often backfire: it limits patient access to studies, slows down drug development and inflates costs.
“When a CRO is involved in the trial, academic researchers are almost completely cut off from the pharma company; you have an organisation in the middle whose goal, almost by design, is for you not to ask questions,” says Prat. “We don’t think that’s efficient or serves patients well. Cancer is already very complex and we need all the help we can get.”
Believing that this model is inefficient, and the separation between investigator and sponsor artificial, MD Anderson’s Strategic Industry Ventures group has been working for some time to cut out the middleman. It now has more than 50 research partnerships and alliances with pharma companies.
“The BMS collaboration was the first one where we had an equal say on the trials that get done, and how they’re designed and executed,” Prat adds. “If it’s not strategic for the pharma company, they won’t want to do it, and if we think it’s going to compromise the patient safety, we’re not going to do it, so it needs to be agreed by the two.”
As he explains, BMS made a financial commitment to cutting bureaucracy, allocating a set level of funding to the programme at the outset. This meant there was no need to waste time negotiating on a trialby- trial basis. What BMS got in return was scientific expertise from the researchers who were actually conducting the studies.
“Under the old framework, companies would have scientific advisory boards that meet maybe once a quarter – that doesn’t cut it,” Prat states. “Here, the people who are doing the work are the ones who advise on the protocol design, the challenges and toxicities that are anticipated, and how we handle those. A close interaction can bring all these aspects together in a more efficient fashion.”
Is collaboration the key?
The clearest advantage of this research model is, perhaps, the fact that it allows researchers to arrive at findings more quickly, speeding up the notoriously protracted drug development process.
“Our idea was to explore the power of checkpoint inhibitors in certain leukaemias,” says Prat. “If we had done this one by one, the way it’d have been done traditionally, it would have taken forever. But since we ran several trials at the same time, we’ve already seen several positive signs of efficacy.”
On top of this, the researchers were able to widen access to their trials to include certain high-risk patients who would have been ineligible under CRO restrictions. This is particularly advantageous in the case of rare diseases like leukaemia, where patient recruitment can be tricky.
Because this cancer research model is flexible and modifiable, the MD Anderson team believes it is well suited to more widespread use. Prat believes we may see a movement towards deeper collaborations in future.
“It’s not for everybody; for example, the BMS collaboration would not have been possible in many places because you need a certain number of patients,” he explains. “If you’re a centre that sees relatively few patients, then a different model is needed that pools your resources with other institutions – and then things get more complicated. But for elite centres with the volume and expertise, I do think this is the way to go.”
He feels that, while using a CRO might be justifiable for a 50- site phase III trial, it’s not the most efficient approach in the earlier stages of research; in fact, he describes their use in proof-of-concept studies as completely counterproductive.
He also thinks that historical tensions between industry and academia are starting to be put to rest.
“Decades ago, there was a slightly antagonistic relationship between research institutions and the pharmaceutical industry, where the industry was seen as a little bit of a necessary evil,” he states. “I think that’s changed, and it’s changed completely at centres like ours, where we see the industry as a partner. If we want to defeat cancer, we need all the smart people we can use.”
A partnership that sets the standard for future cancer research
At the offset, BMS and MD Anderson’s novel clinical research collaboration aimed to evaluate multiple immunotherapies, including Opdivo (nivolumab), Yervoy (ipilimumab) and three early-stage clinical immuno-oncology assets from BMS, as potential treatment options for acute and chronic leukaemia, as well as other haematologic malignancies.
The agreement represented a new approach to research by concentrating on various clinical trials using multiple agents (in mono and combination regimens) on a specific disease target – in this case, select haematologic malignancies. With this strategy, BMS and MD Anderson have strived to benefit patients by speeding up the delivery of new therapies.
The collaboration initially sought to launch up to ten phase I and II clinical trials, conducted by MD Anderson, focused on evaluating investigational immune-based approaches for acute myeloid leukaemia, chronic lymphocytic leukaemia, CML, myelodysplastic syndrome and myelofibrosis.
“BMS is committed to advancing the field of immuno-oncology, and complementing our broad research and discovery programmes through innovative collaborations with partners who share our commitment to patients,” said Francis Cuss, executive vice-president and chief scientific officer at BMS, in a statement. “Cooperation between industry and academia offers a tremendous opportunity to strengthen our scientific and clinical understanding of the role of the immune system in treating cancer.”
Source: BMS
