One of the more intriguing aspects about the new wave of cell and gene therapies (CGT) coming onstream is that they are not just technologically innovative in terms of the sheer novelty of the medical science, but they are also serving to upend the traditional operating model of the pharma industry and break down longstanding silos, barriers and partitions.
“If there’s one thing that has become increasingly apparent, it is that the successful roll out of CGT necessitates entirely new modes of collaboration and stakeholder engagement,” confides Lev Gerlovin, Vice President at the life sciences division of Charles River Associates. “Drug developers aspiring to enter this space all of a sudden find themselves having to forge novel styles of partnerships and risk sharing arrangements that would previously have been considered unthinkable, even only a few years back.”
Indeed, practically overnight, the rules of engagement with manufacturers, academic research centres, payers and healthcare providers, not to mention patient advocacy groups, appear to have been re-drawn and redefined as regenerative medicine becomes more commonplace. There is a certain amount of role-reversal and blurring of responsibilities underway as well: many drug makers are finding that they have to, for the first time, start concerning themselves with aspects of healthcare provision, while clinics and hospitals are contemplating the prospect of incorporating on-site manufacturing capabilities. Part of this is clearly down to the propensity of CGTs to be truly patient-centric.
Hitherto merely a buzzword deployed to signify the social conscience of drug makers, the concept of patient centricity has suddenly taken on a fresh level of meaning with the advent of precision medicine technologies such as CAR-T, which require pharmaceutical firms to extend well beyond their traditional role of just being purveyors of product.
“Within the pharma industry, companies often like to claim to be patient-oriented, but with cell and gene therapies, it becomes absolutely fundamental,” explains Stefan Hendriks, Global Head for Cell and Gene at Novartis Oncology. “Patient centricity is unavoidably part of our DNA because we are working with the patient’s own living cells, so the patient is necessarily central to the majority of the processes being undertaken.”
“In the commercialization of CAR-T, over 25 different roles need to interact to deliver a single treatment to a patient, elaborates Emanuele Ostuni, Novartis Oncology’s head of cell and gene therapy for Europe, who has been assigned the task of overseeing the rollout of the company’s flagship CAR-T therapy across the continent.
“These roles include external collaborators such as nurses and physicians in the treatment centres, logistic partners for the cell’s transport as well as highly specialized internal experts including cell laboratory staff, quality control technicians. Together these teams constitute a ‘dynamic organism’ that cannot be steered in a simple, top-down, command and control manner that the pharma industry tends to be familiar with from the era of chemically synthesised molecules,” he explains.
In the commercialization of CAR-T, over 25 different roles need to interact to deliver a single treatment to a patient
Emanuele Ostuni, Novartis Oncology
Manufacturing Touches Commercial
Yet another of the peculiarities around the development of CGTs is, of course, the unprecedented level of integration between the clinical sphere and commercial manufacturing, which again lends itself to an enhanced level of synergy between those different elements of the value chain.
“In CGT it is absolutely critical that each portion of product development cycle is integrated and that there is a seamless interaction between R&D and manufacturing because you don’t enjoy the luxury of a product going to phase three trials before needing to be ready on the CMC side,” explains Diane Blumenthal, former Head of Technical Operations at Spark Therapeutics. “As soon as you register any kind of clinical efficacy you, proceed straight on to phase 3, so time frames are significantly condensed which can only be accommodated by robust, harmonious teamwork,” she adds.
Christi Shaw, CEO of Kite Pharma very much concurs. “Pretty much straight from the outset through quality inspections, audits and the tracking of the patient, the commercial, quality assurance and manufacturing teams have work together in tandem. This represents a thoroughly different interaction to what we would usually witness” agrees Kite pharma
Securing clinician buy-in
Nor does enhanced collaboration end with the extraction and manufacturing, but instead carries forward to the distribution and partnerships with the hospitals administering the treatment. “One of our biggest initial learnings was that clinics, which hitherto constituted just your client, suddenly take on the additional mantel of being suppliers for cell and gene companies because it is they that collect and provide the cells that comprise the starting material for the final product. This fundamentally reformats the relationship and requires a different sort of collaborative mind-set,” recalls Hendriks.
“It is especially important to secure the buy-in of clinicians,” agrees Thomas Szucs, Director of the European Center of Pharmaceutical Medicine at the University of Basel and Chairman at the Swiss insurer, Helsana Group. “This, of course, entails understanding the technology and the patient need, but equally an adaptation to more interdisciplinary discussions,” he ventures. “Increasingly, I think we will be discussing the question of whether the patient should receive a specific therapy from within dedicated multidisciplinary tumour boards that will be much more molecularly driven,” he predicts.
Fresh types of entities are also proliferating that seek to bring stakeholders even closer together and enable ever smarter interactions between then. The GoCART Coalition, for example, has been establishing a registry across the continent and developing a common educational program for the medical centers and hospitals administering cell and gene therapies. “Currently, each drug maker developing CGT has their own process. Imagine if you have ten approved products from ten manufacturers, the hospitals have to undergo ten different training programs, which is a little impractical. The coalition is therefore working towards establishing a qualification or accreditation system to certify hospitals in a standard way of administering such therapies,” reveals Professor Nicolaus Kröger, President, European Society for Blood and Marrow Transplantation (EMBT)
Equally interesting, is the newfound collaborative spirit that initiatives like the GoCART coalition embody. “For us, it was critical to build a coalition that is win-win for everyone. It is challenging because there is so much competition in the field, within the industry but also within the academic community, since we compete on publications, impact factors and so on. Therefore, we wanted to be careful about how we approached this. The first thing we did was to reach out to the European Hematology Association (EHA), which had always been a competitor of sorts. The idea was to show that, if two major scientific societies for hematology and stem cell transplantation in Europe could work together, other competing groups across academia, industry and elsewhere would also work together,” recalls Kröger.
“We understand that different stakeholders have different interests. The idea is to generate some consensus that can benefit everybody – and especially patients, who are the most important stakeholders at the end of the day,” he stresses.
Long considered by industry to be difficult actors to satisfy, even top regulators such as the FDA and EMA seem to be doing all they can to get these breakthrough therapies of the ground and to forge the levels of multi-stakeholder partnership and consensus needed to support them. “I resolutely encourage sponsors and companies to continue knocking on our doors and to suggest improvements and changes we can make. The need to think of us as partners not opponents,” affirms Ana Hidalgo-Simon, Head of Advanced Therapies at the European Medicines Agency.
“We are operating in a global environment, where these new developments and therapies represent the future, and we must not be fragmented, whether at the top level across international regulators, the second level within Europe and EU member states, or the third level across entities such as research centres, academies, hospitals and clinics,” she insists. “We need to think and work together in a truly joined-up and inclusive manner with everyone sitting at the same table contributing to a common endeavour.”
Her message is therefore one of steadfast and unwavering support. “One important aspect of advanced therapies is that we realize that we need to engage and work with academics a lot more because many of the ideas and initial research actually come from that community, who have not traditionally been commercial drug developers. Therefore, they are less familiar with the regulatory and clinical development processes, the post-authorization requirements, large-scale clinical trials. The onus is therefore upon the rest of us to help them out,” she declares.
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