In December, Novartis posted a letter to the spinal muscular atrophy community, announcing a plan for a global managed access program to provide its gene therapy Zolgensma at no cost to patients in areas of the world where it was not yet approved.

Because of supply constraints, the company said it would provide 100 doses through the program in 2020 to eligible patients with SMA who are under the age of two and are a citizen or legal resident of a country where the therapy is not yet approved. To ensure fairness, the company said it would use a lottery to select which patients received the medicine. At the time, Novartis’ subsidiary AveXis had a single facility to produce the gene therapy even though it was working to expand those capabilities.

“AveXis designed a program anchored in principles of fairness, clinical need, and global accessibility to best determine the equitable global distribution of a finite number of doses that doesn’t favor one child or country over another,” the company wrote.

Though the approach was meant to be a fair means of doling out the potentially life saving treatment, it has been a source of consternation within the patient community. Though Novartis is not in the business of giving away a $2.1 million therapy to all comers, it does represent one of the bizarre consequences of a shortage of manufacturing capability for gene therapies that exists today.

That, however, should be changing as a multibillion building boom is underway to create new capacity for both experimental and marketed gene therapies. It comes as an estimated 800 gene and gene-modified cell therapies were in clinical development as of the end of September 2019, according to the trade group the Alliance for Regenerative Medicine.

“What keeps me up at night is will we be able to manufacture these on a scale that will allow us to bring the benefit of these therapies to patients?” said Peter Marks, director of the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research.

Marks made the comment last week in response to news that Discovery Labs and Deerfield Management launched the Center for Breakthrough Medicines to address the lack of capacity for cell and gene therapies. The $1.1 billion center, hailed as the largest cell and gene therapy contract development and manufacturing organization, will be housed in 680,000 square-feet of space, part of a 1.6 million life sciences campus in King of Prussia, Pennsylvania.

The Center will provide preclinical through commercial manufacturing of cell and gene therapies and component raw materials.  It offers process development, plasmid DNA, viral vectors, cell banking, cell processing, and support testing capabilities all under one roof. The company expects to hire more than 2,000 team members within the next 30 months.

Days later, Krystal Biotech, which is developing gene therapies for rare diseases, broke ground on a second commercial gene therapy facility in Findlay Township, Pennsylvania, a project expected to cost up to $90 million. It expects to have the 100,000 square foot facility finished and validated in time for the expected launch of B-VEC, its lead experimental gene therapy for the treatment of dystrophic epidermolysis bullosa, a rare and often fatal skin blistering condition.

And just a week before the announcement of the Center for Breakthrough Medicines, Nationwide Children’s Hospital unveiled Andelyn Biosciences, a for-profit company that will manufacture gene therapy products for industry.

“The goal of Andelyn Biosciences is to support the advancement of novel gene therapies for rare genetic diseases by building commercial manufacturing capacity which is needed as more of these treatments are developed over the coming years,” said Dennis Durbin, chief scientific officer of The Abigail Wexner Research Institute at Nationwide Children’s.

The activity this month accelerate efforts over the past year. That includes Pfizer’s decision in August to invest $500 million into a gene therapy manufacturing facility in Sanford, North Carolina, an expansion of its initial plans to invest $100 million into the site. A month later, it acquired land and a facility in Durham, North Carolina for $19 million. The building will be retrofitted to double the company’s gene therapy production capabilities.

Novartis, which markets Zolgensma through its subsidiary AveXis, is expanding its manufacturing capabilities with a $500 million investment in new gene and cell therapy facilities. The U.K.-based Orchard Therapeutics is building out a 150,000-square-foot gene therapy manufacturing facility in Fremont, California at a cost of up to $90 million.

And Harvard and MIT late last year announced that they were leading a $50 million public-private effort to establish the non-profit Center for Advanced Biological Innovation and Manufacturing, which is intended to help overcome bottlenecks to getting new treatments into the clinic. It notes scientists may need to wait as long as 18 months to get viral vectors that comply with regulatory standards from contract manufacturers because of existing backlogs.

“Improving manufacturing methods and capacity will be immensely important as the gene therapy sector continues to grow,” said Michael Lehmicke, director of science and industry affairs for the Alliance for Regenerative Medicine. “With the number of regenerative medicine clinical trials and approved products expected to grow exponentially over the next few years, it’s imperative that the sector continue to invest in scalable manufacturing opportunities.”

The expanding capacity is good news. It not only means, but also represents, a critical step toward accelerating the development of new curative and life-saving therapies. Soon drugmakers may not have to rely on the luck of the draw to determine who gets a gene therapy. Perhaps then we can work to figure out a way that patients don’t need to win a lottery to pay for them.

Image: The Center for Breakthrough Medicines, part of a 1.6 million-square-foot life sciences campus in King of Prussia, Pennsylvania

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