On the surface at least, new Food and Drug Administration chief Norman Sharpless is joining the agency at an ideal time. Analysis from consultancy firm Cowen and Company said that the FDA is “operating at peak efficiency during a period of unprecedented innovation” under Sharpless’s predecessor, Scott Gottlieb, who is resigning for personal reasons.
Yet, the picture is altogether murkier. Gottlieb has weakened the FDA and furthered Donald Trump’s deregulation agenda. The agency, it seems, is deep in the pocket of Big Pharma, reflected in the sheer number of unproven drugs and risky therapies being fast-tracked through the approval process.
Industry interference
Concerns about Gottlieb’s relationship with industry dogged him since he was first nominated by Trump back in spring 2017. During a Senate hearing to consider his appointment, Democrat Patty Murray said the physician was mired in “unprecedented financial entanglements,” alluding to his previous role on several pharma industry boards. It was always feared that Gottlieb, who had written various articles decrying pharmaceutical regulations, would be just another of the industry lackeys Trump has appointed to defang America’s key public bodies.
Gottlieb certainly talked tough throughout his two-year tenure, reserving his greatest ire for teenage smoking, or ‘vaping’, which has been hit with a series of restrictions, including a ban on flavored e-cigarettes nationwide. Even as he prepares to leave office, he is threatening to ban the Juul brand that has proved so popular among teenagers. Conservatives have accused him of inciting a “regulatory panic” and lawmakers have even tried to water down some of his anti-vaping measures.
But Gottlieb’s bullish rhetoric hasn’t always been matched by his actions. While threatening to blitz the vaping companies, he’s been rebuked in some quarters for delaying new measures to take e-cigarettes off the shelves. His agency has also stalled new regulations requiring growers to test their water for pathogens, citing Trump’s demand that regulators slash their red tape. Six months after the FDA announced its policy, an outbreak of E. coli linked to infected water canals left five people dead.
Most notable of all was the agency’s treatment of Big Pharma, whos einfluence over the FDA has long been a source of concern. Analysis of transactions made during Barack Obama’s administration showed that a majority of the agency’s drug approval advisors received payments from industry. This represented a clear conflict of interest – one that could encourage the regulator to fast-track drugs that aren’t ready for commercial roll-out.
Frenzied roll-out
Gottlieb, as ever, talked a good game. He even named and shamed those drug companies that blocked cheaper, generic medications. Yet he has also actively encouraged manufacturers to commercialize their products at a furious rate. New drug approvals reached an all-time high last year, and the five-year approval average is now twice as high as it was a decade ago. To critics, many of these drugs are risky, approved too early in a bid to satisfy the companies making them.
The most controversial of all the new drugs is Dsuvia, an opioid 10 times more powerful than fentanyl. Given Gottlieb’s stated intention of curbing the opioid industry and getting to grips with what he described as the “biggest crisis facing [America’s] public health officials”, the approval was particularly jarring: it simply reflects the influence of Big Pharma, which now provides 75% of the funding to the FDA’s opioid division. The agency’s own opioids advisor has condemned the FDA, saying it is “causing people [to] drop dead on the streets” by waving through new high-strength painkillers without sufficient scrutiny.
Also alarming is the unchecked rise of gene therapy, of which Gottlieb was a committed advocate. He has tried to speed up the review process for this form of treatment, which strives to replace faulty genes and is still at a very early stage of development. In January, the FDA announced that it hopes to be approving up to 20 new therapies a year by 2025.
However, many of the risks around gene therapy have yet to be addressed. As scientists continue to point out, the method of transporting new genes to their target cells, via viralvectors, remains a work in progress and prone to error; the delivery method has been found to cause leukemia in certain patients. Then there are the concerns around therapies such as Zolgensma, which has been developed to treat a rare form of spinal muscular atrophy (SMA)in infants.
The FDA awarded primary Zolgensma with primary review status in December, leaving it just six months to make the approval decision. Yet serious questions remain about Zolgensma’s long-term effectiveness, with only 15 people being treated in Phase 1 trials of the therapy, compared to 6,000 patients already being treated by other tested drugs for SMA that are on the market. Then there is the Zolgensma price: early forecasts suggest the therapy could cost up to $5 million. It’s hard to see how these doubts can be assuaged between now and May.
Profit over people
Cynics will say there’s a simple reason for the FDA’s haste: gene therapy promises to be an untold cash cow. Novartis, the company that manufactures Zolgensma, predicts sales of $1.3 billion in 2020; analysts believe gene therapies could regularly cross $1 billion in annual revenues, even when patient populations are small. With each genetic mutation thought to cause 5,000 rare diseases, the market could dwarf that of conventional drugs – and, given the relationship between the FDA and the industries it purports to regulate, this is great news for both parties.
When Gottlieb steps down in April, will Sharpless attempt to disrupt this cozy relationship? Or will he conclude that, with so much money at stake, it pays to be in Big Pharma’s pocket?
Doubtless, Sharpless will come out with plenty of tough talk, just as Gottliebdid. But, like Gottlieb, he is an industry veteran, having helmed two biotech startups. And he joins at a time when Trump is racing ahead with his deregulatory crusade, with no sign of turning back. The new appointee, an oncologist, surely carries plenty of good intentions. But he’s walking into an agency where profit has long since established priority over people.