Two years on from the introduction of Novartis Oncology’s CAR-T therapy to Europe, Emnuele Ostuni, the firm’s European head of cell and gene therapy, spoke to PharmaBoardroom about the pioneering product’s journey to market, what has been learnt along the way, and how his team has worked to assuage concerns around safety, efficacy, and pricing.
Collaboration and Learning
Ostuni highlights “collaboration” and “learning” as the two words that sum up the journey to market of Novartis Oncology’s chimeric antigen receptor T cell (CAR-T) therapy for use in paediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia.
As with all pioneering journeys, we have to constantly be alert to learn from our steps and course-correct where necessary
“We pioneered the therapy and the approval but had to do this by collaborating with many stakeholders,” he notes. “This journey started in 2012 with the University of Pennsylvania where the scientific and medical foundations for Novartis were laid when Emily Whitehead, a 6-year-old child, terminally ill with treatment-resistant leukaemia, was successfully treated with the CD19-CAR-T therapy that later on Novartis licensed in. Today, she is a healthy and happy teenager!”
“When we started the clinical trial program, we had to collaborate very closely with physicians and patients as well as manufacturing partners. As the therapy became more broadly used were learned together how to treat patients in a real-world setting, sharing information, and updating guidelines.”
“Throughout the journey we needed to collaborate with manufacturing partners, supply chain partners, patient organisations, regulators, policymakers and payers –jointly we were building an understanding how to manage the complexity of the therapy on the one side and a sustainable access scheme on the other side. As with all pioneering journeys, we have to constantly be alert to learn from our steps and course-correct where necessary.”
A New Paradigm
As with any ground-breaking new innovation, systems and attitudes have had to become accustomed to CAR-T therapies, especially given that the list price of Novartis’ product can be as high as USD 475,000. As Ostuni states, “Novartis’ CAR-T is a one-time therapy with a multi-year impact. In the beginning, many were not familiar with this new paradigm. We had to innovate collaboratively, learning what was and what was not working from other parties in order to deliver the therapy to patients in dire need of therapeutic options. Transparent collaboration with our partners in a learning mode is key to address these challenging questions without obvious answers.”
In terms of safety concerns, he points out that these relate “to the uniqueness of the therapy. As a patient’s own cells are the basis of the medicine, a so-called “chain of identity” is of paramount relevance. If ever two batches are incidentally interchanged, and patient A would receive patient B’s cells, both are likely to die. So even something seemingly simple like the look of a product label becomes a significant question. For traditional therapies, the name of the product would suffice. But for Novartis’ CAR-T, a patient’s full name and date of birth become part of the batch ID – in Europe, this raised hitherto unknown data privacy challenges which we had to manage collaboratively with regulators.”
Pricing conversations have been, in Ostuni’s words, “not surprisingly…complex.” He continues, “While payers consistently recognised the value of the product, they were not used to the concept of a one-time therapy with multi-year effect. Most of today’s innovative therapies are for chronic disease management and payers are used to reimbursing over a period of time. Since every healthcare system has its own, unique aspects and we realized that cell and gene therapies are often a magnifying lens to existing problems and that we could not take the same approach in every system. Therefore, we collaborated with each payer to find solutions that matched their needs, as long as they could recognize the value of the therapy.”
Other challenges that have arisen include the fact that “Given their complexity, today’s commercial CAR-T therapies are only licensed for administration in specialized treatment centres. These hospitals are trained and qualified by Novartis. One of our biggest learnings was that clinics – which are usually clients “only”- become “suppliers” for pharma companies. They collect and provide the cells that are starting material for the final product. This fundamentally new relation requires specific regulations and a new, collaborative mindset.”
Ostuni adds that, “Internally, we had to create new roles to appreciate all these different challenges, for example the experts who train and qualify the treatment centres or those who accompany the product ordering process throughout the whole manufacturing journey. We also had to develop an IT platform that allows physicians to place orders. Over the course of time, we have worked closely with physicians to continuously improve that platform. We are still working on that to make sure it meets our needs.”