With the genomics revolution now entering full swing, expectations for the future of cell and gene therapy have never been higher. “Gene therapy, somatic-cell therapy and tissue engineering are actually all technologies that have been the subject of research for decades, but look finally mature enough to be ready for prime time,” enthusiastically observes Pierre Meulien, executive director of the Innovative Medicines Initiative (IMI).
Certainly the number of treatments under development is advancing at a frenetic pace. The US FDA has been witnessing a surge in Investigational New Drug (IND) applications relating to this space, with the American regulator now projecting that, by 2025, new approvals for cell and gene therapy products will be coming on stream at a rate of in between 10 and 20 per annum. Meanwhile, Samarth Kulkarni, CEO of CRISPR Therapeutics, has bet that, “by 2030, a full one-third of therapies will be cell and gene-based!” Little wonder the value of the global cell and gene market has been skyrocketing. Coherent Market Insights (CMI) is now projecting a compound annual growth rate of roughly 22 percent, which would see the sector exceeding a total value of USD 35 billion by 2026.
Most fascinating of all is the disruptive aura this new class of medicines is expected to wield. “We are undergoing a transformative moment whereby the development of personalized therapies will start to unleash new modalities. Cell and gene therapies will sing to a different tune to what we have hitherto become accustomed to. Fee-for-service will be replaced by fee-for-outcome, and the old-style pharma model of developing a drug and sitting on a patent for 20 years will become obsolete. Just like the technology industry, new generations of products will be coming out every two or three years, and continuous innovation will separate the winners from the losers,” envisions Kulkarni.
Others, however, ponder whether the international healthcare community really is ready to embrace such an overhaul. While the technical hurdles to manufacturing at scale, and the exorbitant price tag commanded by many of these new medicines are often cited as two major impediments to the ability of cell and gene therapies to go mainstream, the lack of a clear enabling ecosystem may prove equally obstructive.
Novartis’ experience as the first-ever drug maker to secure reimbursement for a cell and gene therapy across many European markets is perhaps illustrative of the sheer enormity of the challenges ahead for this fledgeling industry. “In Europe, we had to assemble from scratch an entirely new commercial organization and with it a network of qualified hospitals, operational and legal structures for the transport of the native cells to the manufacturing site and the transport of the genetically modified CAR-T cells back to the treatment centres. In short, the entire supporting infrastructure,” recalls Emanuele Ostuni, Novartis Oncology’s Head of Cell & Gene Therapy for Europe.
Regulatory and societal complications were also endemic. “Although the therapy had been explored during clinical trials within Europe, a complete new regimen needed to be established to protect the cell’s chain of identity throughout the process, because if ever two bags of cells were to be wrongfully exchanged, both lives would be endangered,” he continues. “It was as if the entire cosmos had to be reshaped… The vast amount of operational, legal and societal issues we faced was frankly astonishing and we realized, that in many respects, traditional approaches of healthcare systems and policies were simply not yet prepared for the onset of cell and gene therapies,” acknowledges Ostuni.
Describing the entire process as an “intensely collaborative journey,” Ostuni recalls how radically new styles of relationships had to be forged with healthcare providers, manufacturers, suppliers, patient organisations and payers. “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 redrawn relationship requires a completely fresh, collaborative mind-set,” he argues.
Though future cell and gene firms will no doubt enjoy a certain amount of second-mover advantage, developers will nonetheless still need to solve the many logistical headaches that come with commercializing these very special products. “Where do you source your cells? How do you keep them safe? And how do you deliver your product intact to the patients as speedily as possible after manufacturing? These are the sorts of weighty questions that companies have to confront and identify fixes for. In the absence of clear guidance, protocols and a supporting apparatus, firms are basically finding they have to improvise each and every tiny detail along the supply chain all by themselves,” says Setsuko Hashimoto, president and CEO of Tokyo-based stem cell company CellSeed Inc.
“Many big pharma multinationals have been struggling to position new cell and gene therapy offerings within traditional monolithic operational models, which favour supply chains built around products, are push-based, and are heavily reliant on inventory. This is because individualized cell and gene therapies require a clinically connected value chain that is built around patients, highly agile, and usually pull-based,” observes Omkar Kawalekar, NextGen Therapy Practice Manufacturing Lead at Deloitte. He is therefore urging his clients to instead design their value chain from an outside-in, patient-oriented perspective, so that the enabling digital core and its components – systems, databases, and tools – provide end-to-end value chain visibility and an opportunity for broad interconnectivity.
Even sourcing the requisite talent to support one’s operations can prove tricky. “In a young industry experiencing rapid growth like this, talent demand far outweighs supply. One witnesses products failing in many markets, yet this is often not down to the science itself, but because the businesses lack the appropriate personnel who are sufficiently qualified, experienced and intellectually equipped for the task at hand. It will take time for all of this to normalise” warns Steve Smith, Head of Rare Diseases and Cell & Gene Therapy at Next Phase Recruitment. Indeed, companies like Novartis have been busy creating an entirely new cadre of professional roles from scratch: from the experts who train and qualify the treatment centres to those who accompany the product ordering process throughout the manufacturing journey.
Quite how long it will take for cell-based healthcare to become commonplace remains anyone’s guess. That it is coming, however, is a certainty. “Ultimately patients demand cures, and with cell and gene therapies looking all set to deliver on that front, there can be absolutely no going back!” concludes Reh.