- The hottest new area of medicine today is a cutting-edge technology that leverages the body’s own cells to treat disease.
- Companies have been pouring in and investing billions. But they’re encountering one big challenge: actually making the treatments.
- New gene and cell therapies are encountering years-long backlogs, and delays keep potentially lifesaving medicines away from patients.
For the biotech company Meira Gtx, a 29,000-square-foot factory in central London is the solution to a problem that has bedeviled its entire industry.
The $660 million startup develops cutting-edge gene therapies, which tinker with the body’s DNA in hopes of treating serious illnesses. Meira focuses on a number of diseases of the eye, salivary gland and brain.
The company had only just started in 2015 when a huge opportunity opened up, to lease a drug manufacturing facility from a leading UK eye hospital. Meira jumped at it, quickly hiring pharma veterans to build out its capabilities and take over manufacturing, snapping up its new head of quality from the Swiss drug giant Novartis.
Gene therapy is the hottest area in medicine, offering up the potential to treat or even cure devastating rare and not-so-rare diseases. Gene therapy and a sister field, cell therapy, attracted more than $13 billion in global financing last year, by an industry group’s count. Some products have already been approved in the US, and many more are in the works, with more than 1,000 research trials ongoing.
But first, companies have to make the medicines. In a field so new, trendy, and intensely complicated, manufacturing has become a crucial, costly and time-consuming challenge, with a surge of new interest forcing biopharmaceutical companies to either build their own multimillion-dollar facilities or else wait on lines for years for others to manufacture them.
Meira’s enviable capability has sparked requests from other companies to make their products. And it could well explain an up to $440 million partnership the biotech inked with Johnson & Johnson’s Janssen earlier this year, focused on both research and improving manufacturing.
"Manufacturing is critical to us," Alexandria Forbes, Meira Gtx’s president and CEO, said in an interview with Business Insider. "It’s an industry-wide issue."
The biotech deliberately focused on disease areas where it wouldn’t need to make huge amounts of the product, Forbes said. But other companies are facing the challenge on a much bigger scale.
“If you don’t control your manufacturing, you don’t control your fate,” said Katherine High, Spark Therapeutics’ co-founder, president and chief scientific officer, speaking at the Gene Therapy for Rare Disorders conference in Boston, Massachusetts last month. Spark is currently being acquired by Swiss drug giant Roche for nearly $5 billion.
The challenge has also prompted deals among third-party companies that manufacture gene therapies, including one this week. On Sunday, The Wall Street Journal reported that the manufacturer Catalent is buying privately-held Paragon Bioservices in an all-cash deal for $1.2 billion.
Bottlenecks, backlogs, and millions of dollars in the balance
Imagine you’re a successful home baker, turning out dozens of warm cookies each weekend for friends and family to enjoy.
To put out 12,000 cookies instead, your homegrown operation, with its little mixing bowl and standard apartment oven, would need to change dramatically.
Except in gene therapy, you can’t just multiply the recipe.
Companies are working with viruses or living cells, so "it’s not an exact science" in the same way, he said.
Whether companies are vying for slots at the contract manufacturing organizations (CMOs) that make the very specialized medicines, or trying to build their own factories, manufacturing has become a bottleneck for companies.
Both routes are expensive. Hiring an outside organization can run in the neighborhood of $7.4 million just to get to the point where a company is able to test its products in humans, while doing the work in-house can come to about twice that, or $14.7 million, Mustang Bio Chief Technology Officer Knut Niss estimates.
It’s better to choose the in-house route if a company is doing a lot of manufacturing and research, Niss said last month at the Boston gene therapy conference.
Companies are also encountering long wait times to get their products made or to buy the requisite, ultra-specialized equipment.
"When everyone decides to order 600 hyperstacks, you can suddenly have some challenges. And some of us have experienced that," said Christopher Murphy, chief operations officer at Brammer Bio, which is being acquired by Thermo Fisher for about $1.7 billion in cash.
Murphy was referring to an essential piece of equipment employed in gene and cell therapy manufacturing.
With any delay, lifesaving medicine is on the line. On one collaboration Project Farma did with Novartis’s AveXis, delays of even a day mean that "hundreds of babies are potentially not going to have the ability to get this treatment," Khoury said.
"The queue in contract manufacturing is actually slowing down investigating these therapies and getting these therapies to patients," said the US Food and Drug Administration’s top official overseeing gene therapy, Dr. Peter Marks.
A field pioneered by academics ‘then had to work backwards’
It wasn’t always obvious that treating disease at the genetic level would even be possible.
Two decades ago, at least one high-profile patient death in a research trial of a gene therapy prompted skittishness from companies and investors.
Pioneering work by university researchers ultimately powered the field’s success today. But that background has contributed to its struggles, too.
Once the data was promising, researchers "then had to work backwards, figuring out the manufacturing and controls," said Brian Kaspar, chief scientific officer of Novartis’s AveXis, who was one of those researchers before he joined industry.
AveXis has invested heavily in its manufacturing capacity, which it has long seen as crucial for its future, Kaspar said.
Manufacturing is such a broad problem that industry group Alliance for Regenerative Medicine (ARM) is working on a how-to guide spelling out the process, which it’s calling "A-Gene."
The group was also motivated by recent history. A group of drugs known as monoclobal antibodies, which fight cancer and treat conditions like rheumatoid arthritis, are now among the world’s top-selling treatments. But when the drugs first hit the market, pharma companies encountered complex manufacturing challenges, limiting how many could be made and making those that could be manufactured more costly.
Using a model from that time as a guide, ARM started "A-Gene" in May of last year. Many companies have been involved in the effort, and the group expects to hammer out a draft by the end of the year.
‘For 10,000 patients, that means 10,000 batches’
Around the world, 300,000 to 400,000 people are born with sickle cell disease, an inherited blood disorder that causes serious pain episodes and can lead to an early death.
The biotech Bluebird Bio believes its new experimental treatment LentiGlobin could make a big difference for those who have sickle cell disease.
But developing LentiGlobin hasn’t been easy. Bluebird Chief Technology and Manufacturing Officer Derek Adams calls it "the most complicated process I’ve ever seen."
LentiGlobin entails taking a patient’s blood plasma, modifying those cells outside of the body, and then re-introducing them into the patient by way of an infusion.
Manufacturing gene or cell therapies can thus be a highly individualized, bespoke process, more like a one-of-a-kind boutique than a mass-market chain of stores.
"The patient starts the manufacturing process. That whole manufacturing process centers around the patient," Adams said at the Boston gene therapy conference.
"That doesn’t seem so bad until you realize that if you want to do this for 10,000 patients, that means 10,000 batches."
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