Novartis is teaming up with the contract manufacturing firm Catalent Biologics to boost production of its recently commercialized gene therapy Zolgensma. The announcement is a surprise because three months ago Novartis’ gene therapy subsidiary, AveXis, said it is buying a facility in Longmont, Colorado, for the same purpose. The Longmont site will be the company’s fourth gene therapy manufacturing plant.
Viruses, the essential DNA-delivery vehicles of gene therapy, are in short supply. Gene therapy firms bemoan long waitlists for contract manufacturers, leading many to break ground on their own manufacturing facilities years before a commercialized drug is in sight. For Novartis, which sells one of the few approved gene therapies, even having its own facilities isn’t enough.
The demand has more to do with the complexity of making the therapies than long lines of customers waiting for them. Andy Stober, chief technology officer at AveXis, says the company decided to work with the gene therapy manufacturer Paragon Bioservices at the beginning of the year, before Zolgensma was approved. In April, Catalent bought Paragon for $1.2 billion.
Zolgensma is a one-time injection of viruses containing a corrective piece of DNA to treat young children with a rare neurodegenerative disease called spinal muscular atrophy. It’s dosed at 110 trillion viruses per kg of body weight, meaning that “you are giving someone a quadrillion viral vectors,” Stober says. “It’s no small feat.”
It’s expensive too, costing $2.1 million, partly because of the massive quantities of DNA-stuffed viruses required for the treatment to work. And it’s the creation of those viruses that AveXis needs help with. The firm’s original Libertyville, Illinois, plant has room for purifying and filling the final gene therapy product, but it’s Catalent that will produce the bulk of the viruses.
AveXis is looking to make more of those viruses on its own soon. Its $115 million plant in Durham, North Carolina, is scheduled to open next year. In all, AveXis anticipates that its four plants will create more than 1,000 manufacturing jobs by the end of this year—all to make a commercial gene therapy for a single rare disease, plus experimental gene therapies for a few clinical trials that may begin within a year.
The demand for viruses has been a boon to contract manufacturers. A gene therapy start-up called Passage Bio—which launched earlier this year and won’t have a therapy in clinical testing until next year—recently announced that Paragon will build it a dedicated production suite.
And while new gene therapy companies are racing to beat the manufacturing bottleneck, older companies, including cell therapy firms that also need viruses, are playing catchup.
So far, Novartis and Gilead Sciences are the only drugmakers selling engineered cell therapies, for which every treatment is custom-made from a patient’s own immune cells—a manufacturing headache of its own. The same kinds of viruses used for gene therapy are used to insert new DNA into those immune cells, adding another bottleneck to an already costly and time-consuming process.
Those drugmakers are trying to take matters into their own hands. Earlier this year, Novartis acquired a French cell and gene therapy manufacturer called CellforCure, which was already producing the Novartis cell therapy Kymriah. This week, Gilead announced it will build a 6,000 m2 facility dedicated to making viruses used in its cell therapy, Yescarta.
Bluebird Bio, a company developing cell and gene therapies, opened an 11,000 m2 manufacturing facility in Durham, North Carolina, in March. Bluebird just won approval from the European Medicines Agency in June to begin selling its first treatment, Zynteglo, in which an individual’s own hematopoietic stem cells are engineered with a virus to treat a genetic blood disease called β-thalassemia. The treatment will cost about $1.8 million.
Soon after Zynteglo was approved, Bluebird announced that sales of the treatment will be delayed until 2020 while the firm irons out its manufacturing process.