A blockbuster advanced therapy could lead to a pharma-economic crisis unless the industry works to improve manufacturing efficiency. That’s according to Anthony Davies, PhD, founder and CEO of Dark Horse Consulting.

According to Davies, who specializes in gene and cell therapies, they are following a path previously trodden by monoclonal antibodies (mAbs). Monoclonal manufacturing is a million times more productive than when Herceptin (Trastuzumab) was first approved for U.S. medical use in 1998.  Limited supply meant Herceptin was allocated on a lottery system. Davies believes similar rationing may occur again, due to the cost of advanced therapies.

“Gene therapy products like Zolgensma® treat a relatively small patient population, so if they cost multiple millions, it won’t have a noticeable impact on a nation’s pharmaceutical spending,” he explains. “But there’s a massive pharma-economic problem once a blockbuster cell or gene therapy gets approved, such as for a solid tumor indication or one of the more common genetic diseases.”

Davies believes the industry is close to having advanced therapy drug approved for a blockbuster indication. Roctavian, the first gene therapy to gain conditional marketing approval in Europe for severe hemophilia, is an example of an advanced therapy targeting a more common condition.

Enormously more complex

The high cost of gene and cell therapies is due to their complexity compared to monoclonal antibodies, points out Davies, who adds that “They’re enormously more complex. They’re more expensive to manufacture and more complex to characterize.”

Davies says that mAbs were in a similar position in the 1990s, as they were a huge leap in complexity up from the small molecule drugs of that era, such as aspirin or Viagra. It’s taken thirty years of hard work by companies, such as Herceptin manufacturer Genentech, to increase productivity and decrease manufacturing costs, he continues.

“Hundreds of thousands of scientists at Genentech were working to increase yields, so demand could be met,” says Davies. When he was in graduate school, he explains, mAbs had a manufacturing yield of micrograms per liter, and by the time Herceptin was released, they’d just broken the gram per liter barrier.

“Now, if a mAb doesn’t have a yield of greater than 10 g/L, no one wants to talk to you,” he says. He believes the industry needs to focus on rapid development of new manufacturing processes to drive down costs—to prevent future rationing of drugs.

“We’re sleepwalking into a COGS [Cost of Goods Sold] crisis and I fear history repeating itself,” he says. “I wish we had been far ahead of this problem as an industry, but—sadly—we haven’t.”