In building out its cell therapy manufacturing network, Novartis has established four in-house facilities across the US and Europe.
However, the Swiss drugmaker has also used service providers, for example, by partnering with Germany’s Fraunhofer IZI to access chimeric antigen receptor (CAR)-T therapies for use in its first European clinical trials and the early years of commercial sales in the region.
Novartis has taken the outsourcing route in Japan, too, completing the technology transfer for CAR-T therapy Kymriah (tisagenlecleucel) to Kobe-based the Foundation for Biomedical Research and Innovation (FBRI) early this year. FBRI subsequently supported clinical supply in Japan.
However, while the Japanese regulator approved Kymriah in March, it is taking longer to get the cell therapy contract manufacturer ready for commercial supply. At a recent R&D day, Novartis said the contract manufacturer will be commercially ready in the second half of next year.
Work to get FBRI commercially ready is part of a broader effort by Novartis to establish the capacity to support its global cell therapy ambitions. Currently, Novartis lacks that capacity.
Novartis CEO Vas Narasimhan said, “We are supply constrained on Kymriah. It’s not a demand constraint. Our goal is to work hard to relieve that ... constraint. We continue to be optimistic that Kymriah will reach blockbuster potential within the next five years.”
The comment follows a period in which Kymriah, Novartis’ approved CAR-T, has fallen short of sales expectations. Sales over the first nine months of 2019 totalled around $180m (€163m).
Novartis’ struggles to meet demand for Kymriah reflect the novel challenge of making autologous cell therapies, which are produced by taking a patient’s own cells, processing them and administering them back into the same patient.
Cell therapies are one of a clutch of emerging modalities and therapeutic concepts that are central to Novartis’ pipeline plans. Novartis recognises that it needs to match its infrastructure to the changing mix of modalities in its pipeline, as Jay Bradner, president of the Novartis Institutes for BioMedical Research, explained.
Bradner said, “It’s not enough just to do this in drug discovery, as we have learned. This needs to be a coordinated strategy across the entire enterprise.”
That coordinated strategy has led Novartis to add in-house and contract capacity to support plans to introduce more CAR-Ts and CRISPR-edited stem cells in the coming years. Bradner said Novartis is “building up scale to accelerate all of these programs [going] forward.”
The exact demands Novartis places on that capacity are likely to change in the coming years, with Bradner predicting the future of the field will feature “a new way of manufacturing CAR-T cells”. One big expected change is the arrival of allogeneic CAR-Ts made from donor cells.