The controversial ketamine-like drug that Trump is pushing on veterans

Spravato, developed by Johnson & Johnson subsidiary Janssen Pharmaceuticals, has been billed as a “novel” treatment for depression.

 Spravato, developed by Johnson & Johnson subsidiary Janssen Pharmaceuticals, has been billed as a “novel” treatment for depression. Photograph: Associate Press

Personal interest from Donald Trump appears to have put a controversial anti-depressant on a fast track at the Department of Veterans Affairs (VA) that shoved aside usual protocols, even though experts inside and outside the government have serious concerns the drug is effective and say it may be dangerous.

Sources inside the Department of Veterans Affairs say staffers were essentially told by a senior official to drop everything in March and accelerate the drug’s availability because the president had expressed enthusiasm for the drug, Spravato, as a possible treatment for depressed veterans.

Questions have also been raised about a trio of Trump friends who have been working on veterans issues and interacting with Johnson & Johnson regarding programs for troubled vets.

In the midst of a rapidly convened series of VA meetings early that month, another official said the president wanted the VA to buy “truckloads” of the drug, according to sources. Trump also touted the drug’s benefits to Veterans Affairs secretary Robert Wilkie in a White House meeting just last week, offering to help negotiate the VA’s purchase of the drug, according to Bloomberg.

A key VA panel, the so-called formulary committee, is meeting this week to decide if Spravato, whose formal name is esketamine, will be added to the list of drugs that must be available to VA pharmacies. A vote is expected Wednesday, though a final decision may take longer. Esketamine is a derivative of ketamine, which has been used to treat depression, and has been abused as a party drug.

The stakes are high for the drug’s owner, pharmaceutical giant Johnson & Johnson, because the drug could be a blockbuster. One analysis estimates Spravato could earn $600m for the company by 2022. The drug was developed by J&J subsidiary Janssen Pharmaceuticals. While it was under development, J&J’s and Janssen’s relationships at the VA deepened. As trials for the drug went forward in late 2017, Johnson & Johnson joined the VA’s suicide prevention campaign, #BeThere. A public service announcement on the campaign said J&J and the VA will “undertake new clinical trial processes in hopes of providing access to the latest and most innovative treatments to help veterans in need”.

Janssen said in a statement that throughout its partnership it had a memorandum of understanding in place “that we’ve followed”, adding that the company had “strictly complied with the laws in place that govern partnerships across industry and government related to ethics and conflicts of interest”.

In the course of the drug’s trials, J&J was also involved with a trio of men Trump knew through his Florida social club Mar-a-Lago who became advisers on VA issues.

The three, Marvel Entertainment CEO Ike Perlmutter, Palm Beach physician Bruce Moskowitz and attorney Marc Sherman, were labeled the “Mar-a-Lago Crowd” in a 2018 lawsuit by a veterans group against the VA, alleging that the trio constituted an illegal advisory committee that had outsized influence over Trump’s decisions involving the agency. Much of the lawsuit is based on an article by ProPublica. The suit claims the trio convened a series of conference calls with J&J executives to discuss and promote the public awareness campaign; as part of that effort, then-VA secretary David Shulkin was joined by J&J officials in ringing the closing bell at the New York Stock Exchange on Veterans Day in late 2017.

The VA has moved to dismiss the suit, saying the Mar-A-Lago trio were just individuals giving advice. The three men did not respond to messages from the Center. But in responding to ProPublica, the trio cited Perlmutter’s “personal relationship with the president” and said they “offered our counsel, and the advice of these healthcare experts, to assist the president, secretary and VA leadership in their making essential decisions”. They said this was done voluntarily, “seeking nothing at all in return”.

Records from the Center for Responsive Politics show that J&J was among the firms lobbying most heavily at the VA in 2018. CRP records show that J&J spent a total of $6.6m that year lobbying the federal government about pharmaceuticals and health products; in 2018 and 2019 it lobbied the VA on matters including “partnership with the VA on suicide prevention”. The company gave $14,165 to Trump’s 2016 campaign.

The stakes at this week’s VA committee meeting are high for veterans too, whose ranks have been plagued by depression and suicide. A drug that offers a fast and lasting answer for treatment-resistant depression would be a godsend. But is Spravato that drug? Some say yes. FDA officials writing in the New England Journal of Medicine called it “a novel treatment for a severe and life-threatening condition,” touting its “rapid onset of effect [as] a key benefit.” Janssen called it “the first new mechanism of action” for major depression and said it “can offer significant and sustained improvement of depression symptoms for adults with TRD [treatment-resistant depression].”

A joint FDA advisory committee previously voted 14-2 to approve the drug for release.

But Spravato’s heightened profile has unleashed a storm of questions from academics, psychiatrists, and health researchers with concerns about the drug: how it was approved, how well it works, whether it is safe, how much it costs, and whether it’s right for veterans. The discussion has revealed some unsettling issues:

  • The FDA abandoned a longstanding procedure of requiring two successful short-term trials before approving anti-depression drugs. Instead, when this drug showed itself to be no better than placebo in two of three short-term trials, the FDA accepted the third trial alone, adding on another and different type of trial that some say was deeply flawed. The FDA admitted it had not previously done this, but said it was not “unreasonable”. FDA committee member Erick Turner of the Oregon Health and Science University, who did not make the advisory committee meeting, called the FDA’s position “bull”. “It’s not a reason,” he said. “That’s like a parent saying, “Because I said so.’”
  • Even though the drug is being hurried into use by the VA, some psychiatrists and researchers say the evidence from trials does not demonstrate that the drug works on people over 65 – or, some say, even on males. The VA’s patient population is 90% male and 52% over 65.
  • During several years of trials, six people who had been treated with the drug died, as opposed to none on placebos. Three of the deaths were suicides. Janssen said none were considered by investigators to be related to Spravato. The FDA concurred. Still, noted one professor and psychiatrist, “It’s not heading in the direction supporting protection from suicides.”
  • Data from the drug’s trials shows it to be only marginally better than placebos in its performance, several researchers and psychiatrists said after looking at the data.
  • The dangers of treatment – mainly dissociation, sleepiness, and blood-pressure hikes – are so significant that patients must stay in the doctor’s office for 2 hours after receiving their Spravato infusion. The office must be equipped with equipment to deal with hallucinatory, cardiac, and respiratory problems. The patient cannot drive for 24 hours after taking the drug. “A wonder drug? I think it’s a wonder that’s anybody thinks it’s a wonder drug,” said Diana Zuckerman, president of the National Center for Health Research in Washington DC.

The White House did not respond to questions about Trump’s involvement. Officials at the VA declined to answer a long series of questions, but noted in a statement that the FDA had approved the drug for adults with treatment-resistant depression.

“VA has not yet administered esketamine to any patients, and is in the process of designing a clinical implementation plan optimized for safety and efficacy,” it said.

Janssen defended its trials as proper and said they demonstrated the drug’s efficacy. It said Spravato “represents hope for many patients who have been suffering for some time and have cycled through multiple medicines without relief.” The FDA referred a reporter to a journal article authored by its officials that explained the trials and touted the drug as a “novel treatment” with “rapid onset of effect”.

But a variety of experts have found the sequence of events involving Spravato unsettling. Some VA staffers were uncomfortable with pressure from higher-ups that seemed directly attributable to their perception of Trump’s interest.

If Trump had actually urged the VA to buy the drug, said Michael Carome, director of the watchdog group Public Citizen’s Health Research Group, it would be “completely inappropriate”. In February, Public Citizen sent the FDA a 14-page letter urging that the drug not be approved without more research, citing unproven efficacy and proven dangers.

Carome noted that the VA has perfectly good mechanisms of its own for examining new drugs and choosing appropriate ones for its patients. Presidential intervention, he said, is “just absurd on its face”.

Nevertheless, the VA was in a hurry. In March, staffers scoured their regions to find out what clinics, if any, were outfitted to handle esketamine treatment, and what could be done to add more clinics. A contract with Janssen Pharmaceuticals was signed in 48 hours – far more rapidly than normal – so that pricing could be nailed down. Normally such a contract takes a month or more. Patient consent paperwork was prepared. Staffers created Powerpoints, and a lengthy and detailed paper on the drug, its applications and uses and dangers was rushed into print. Efforts were initiated to equip new clinics to handle esketamine treatments. The press office began work on a statement.

On March 19 – two weeks after the FDA approved the drug – the VA announced that Spravato would be available for its patients. Its press release quoted secretary Wilkie: “We’re pleased to be able to expand options for veterans with depression who have not responded to other treatments.” Staffers were told the goal was to treat the first VA patient with Spravato within 90 days.

But the debate over Spravato has not abated. On May 17, three psychiatrists, Michael D. Alpert and J. Wesley Boyd of Harvard Medical School, and Marco A. Ramos at Yale, published a strongly-worded opinion piece at Vice.com, headlined The New Ketamine-Based Antidepressant Is a Rip-Off. The authors noted the cost of the drug, “nearly $900 per dose, or roughly $7000 for the first months of treatment,” and that the drug proved to be no better than a placebo in two of its three short-term trials.

But “the biggest problem at hand is not the drug itself,” they added. “It’s the fact that instead of representing a revolution in mental health treatment, as it has been touted to do, esketamine is not a breakthrough at all.”

By week’s end, it will be clear whether the VA’s formulary committee agrees.

[“source=theguardian”]