Novartis is confident the manufacturing costs of gene therapies will fall as it improves processes and brings on board next generation technologies such as CRISPR and gene editing.

Swiss Pharma giant Novartis has “always been a company that is multi-modality in really trying to address an unmet need in a number of diseases,” Shephard Mpofu,  chief medical officer at Novartis Gene Therapies said yesterday.

Highlighting the firm’s success in small and large molecules, he reminded delegates at Phacilitate’s Advanced Therapies Week in Miami, Florida Novartis is also one of the pioneers in the cell and gene therapy space. The firm achieved US success for the first CAR-T therapy — Kymriah (tisagenlecleucel) — in 2017 and, through its $8.7 billion acquisition of AveXis, won approval for its spinal muscular atrophy (SMA) gene therapy Zolgensma (onasemnogene abeparvovec) in 2019.

Shephard Mpofu was part of a fireside chat hosted by Dark Horse Consulting’s Robert Allen at Advanced Therapies Week in Miami

During a packed but socially-distanced plenary session, Mpofu referred to Zolgensma as being a “gene therapy 1.0,” and Novartis’ pipeline has now shifted to adeno-associated virus-based (AAV9-based) therapies, representing “the emergence of 2.0.”

By focusing on “really targeted AAVs that have better affinity for the cell types in the respective indication,” the firm can fully understand the benefit risk and deliver “the right amount of dose to the right target with less off-target effect.”

But beyond this, Novartis is looking at the next-generation of gene therapies, 3.0.

“3.0 is really factoring in all the new technologies that are currently being discussed at this conference in terms of CRISPR and gene editing. And we have all this in our arsenal. We think when we look at everything we are focusing on, eg neurodevelopment disorders, neurodegenerative disease, neuromuscular, and also optogenetics.”

He cited recent collaborations and acquisitions as evidence of Novartis’ leadership in the sector, specifically the acquisition of Vedere Bio in 2020, adding ocular gene therapy candidates and an AAV-based delivery technology, and the more recent $800 million addition of Gyroscope Therapeutics.

Reducing COGS

For Novartis, bringing a single-dose gene therapy to market was a major breakthrough, but much focus was on Zolgensma’s $2.1 million price tag, driven by the high cost of goods sold (COGS).

“In terms of manufacturing, everyone understands this has been one of the bottlenecks of advanced therapies because it is very complex, very individual focused, and there is so much that is required in terms of ensuring robust quality, scaling, and sustainability,” he said.

By continuing to invest and innovate in the field of gene therapy, Mpofu added Novartis continually improves its processes, and these improved efficiencies will lead to a reduction in COGS and increase patient access.

However, he reminded the room that it remains critical to “untangle the manufacturing cost from the value of the therapy,” before calling for a paradigm shift in the healthcare funding model.

“From the get-go, we started very early in building and understanding the holistic value of the therapy to the patient, to the caregiver, to the family, to the society, to the healthcare system,” he said.

“We have a team of experts that build models and really understand the value of the therapy. Remember this is a one-time therapy that gives a lifetime of benefit. This is almost a 21st century medicine founded in a 20th century healthcare system for chronic diseases, and what we’ve been doing is really getting into collaborations and discussions with multiple stakeholders to really understand the value of the therapy and get the best value.”