Congress wants only one ALS patient to have a therapy ever tested in humans

WASHINGTON – A family in Iowa thinks the Food and Drug Administration will decide if its only surviving daughter lives or dies, and they are in a crusade that has been going on for months to break up its bureaucracy. And they succeed.

Just last week, the FDA announced to Jaci Hermstad, Iowan, 25, dying of a rare form of ALS, the early sign that she would receive the first dose of Alzheimer's disease. An experimental drug never tested before in humans. The FDA's move, confirmed at STAT by Jaci's family and doctor, is a breakthrough for the Hermstads.

For months, the family circulated petitions, tweeted President Trump, and called some of Washington's most controversial and powerful politicians – including the House Speaker and a Republican under racist rhetoric – to convince the FDA to give up even most of the basic studies before the drug is injected into Jaci's already fragile immune system.

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The progress of the Hermstads is fueling a heated debate in Washington on the role of the FDA in determining when sick or dying patients can access experimental treatments – and on the role that career politicians should play in the decisions of the United States. country on how and when to let patients have access to untested treatments. This also raises a fundamental question about the role of lawmakers: is it fair that a member of Congress intervenes on behalf of a single constituent?

"Do you really want the FDA to respond to the individual demands of the congressist families?" Asked Arthur Caplan, founding director of the medical ethics division of the New York University of Medicine.

The FDA is no stranger to this debate: the issue worsened at the same time last year, when Washington deliberated and finally passed a federal law on "the right to judge" that largely sidesteps the FDA's Determination process upon death, patients can access experimental treatments studied in clinical trials.

The Hermstad case is much more complicated. The drug that Jaci has tried has not been clinically tested, making it ineligible for the pathway described in the Right to Test Act, supported by President Trump. And although Jaci's family felt compelled to pressure Trump and lawmakers to help them, they might not have needed: The FDA had never refused Jaci's request for access to the drug; Regulatory agencies simply requested that toxicology tests be conducted. In fact, Jaci's doctor spoke only good words to the FDA throughout the process.

The chaotic story underscores how difficult it has become to have access to experimental therapies in the United States. It raises many questions about the role of the FDA as a guardian, the merits of Congress acting on behalf of a single patient, the role of crowdfunding pay for basic research, and the most basic and most fundamental issue. heavy of all: who is to blame when a 25-year-old is about to die, and that he can not have access to a drug that, in his opinion, could save his life?

"You have a huge ethical and political quagmire here," said Caplan.

WWhen Jaci's family heard about this medicine in February, it looked like divine intervention. The call took place just one day after Jaci's first diagnosis: Dr. Neil Shneider, head of the SLA clinic at Columbia University, described a new treatment called an antisense oligonucleotide that, at least in theory , could prevent the production of proteins suspected of killing motor neurons in ALS patients.

"It's as if God had paved the way for this event, and there's a reason for that," said Jaci's mother Lori Hermstad.

Soon, however, the Hermstads learned that the therapy was too early in development for them to access it. Its elemental safety and toxicity had not even been examined yet – which meant that the battle would be long and arduous to obtain the drug through the existing FDA pathway for potentially life-saving experimental treatments, known as "Expanded Access Program". The Hermstads also could not rely on the federal law on the right to try Trump had signed in May 2018 because the drug had not been the subject of phase 1 clinical trials.

But the Hermstads were determined not to give up. They contacted local lawmakers, launched a Facebook group called "Cowgirl Up for Jaci" and launched an online petition to the FDA.

The aggressive Hermstad campaign eventually attracted an improbable group of legislators: Democratic House Speaker Nancy Pelosi (California), Senator Chuck Grassley, a powerful chair of the Senate Finance Committee, and her colleague Republican Republican Iowa, Steve King. had been deprived of almost all his power after adopting racist ideas in an interview with the New York Times in January.

King took the most brazen step.

On May 20, the Congressman introduced a bill almost unheard of: a one-sentence bill requiring an entire federal agency to make an exception to its rules for a single individual named: Jaci Hermstad. It has only 40 words.

The bill has never been formally considered by Congress, but it has attracted the attention of some of Washington's greatest lawmakers. King had "multiple productive discussions" on the issue with Pelosi, who ultimately contacted the FDA directly to discuss the Hermstad case, according to a press release from King. (Neither King nor Pelosi responded to requests for comment.)

Republican Senator Chuck Grassley, Senator of Jaci, one of Washington's most influential legislators on health policy, also "urged the FDA and the White House to give full attention to Jaci's request," said Michael Zona, a spokesman for Grassley.

Less than a week after King's bill and Pelosi's intervention, Jaci's family had the first sign that the FDA was withdrawing from its previous requests. Although the FDA did not officially accept or deny Jaci's expanded access request, British Columbia Shneider told STAT on Wednesday that there was "some sagging" of the FDA. He added that the agency seemed ready to give up its previous requests to the pharmaceutical company to carry out significant toxicological studies before the first injection of Jaci.

"I think we may have been lucky because we hit them at a time when there was a lot of external pressure and internal discussion about it, and we were a test case," said Shneider.

(Shneider pointed out that Jaci's first scheduled injection on June 10 would not have been finalized until he received an official FDA response to the expanded access request he had officially tabled on Wednesday.)

TThe few personal interventions by some of the country's highest public officials – and the extremely early FDA exception for its own policies – raise questions about the role the federal government plays in the lives of dying patients. The agency had such questions when Washington began debating a federal law on the right to try: The main task of the FDA is to determine which drugs are safe and effective for Americans. But are there moments, perhaps when life is at stake, that the mission should not be accomplished?

"What the right to try has done, and what single bills such as this one will do, will put us back in a position where we have to justify the existence of the FDA in society," said Holly Fernandez Lynch, a bioethicist at the University of Pennsylvania, who raised concerns with the Hermstad case and with the federal law on the right to judge. "For this particular patient, it seems like an individual decision, but it has a long-term impact on allowing the FDA to fulfill its function."

Congress has the power to craft a so-called private law – bills that apply only to a small group of people, not to the general public. These private bills were written to grant citizenship, alleviate debt and pay for damages caused by government wrongdoing. Senator Hubert Humphrey Jr. even drafted a private bill granting special benefits to former employees of the Senate restaurant.

But experts have expressed concern over the precedent set by a bill designed to help a single patient.

"What does it mean for all the others who are similarly in a very serious situation but who [doesn’t] have the same resources to communicate with lawmakers, the media and the general public through social media? Asked Kelly McBride Folkers, research associate at NYU's Division of Medical Ethics.

In half a dozen STAT interviews with experts on both sides of the FDA's broader access policy debate, no expert was able to point to another piece of legislation that was so clearly trying to force the hand of the FDA regarding the treatment of an individual.

Even Shneider, Jaci's doctor, is worried about political pressure on the FDA. In an interview with STAT, he said the FDA had been "very receptive" and "really responsible" throughout Jaci's treatment attempt.

"Frankly, I did not encourage it," said Shneider, citing congressional pressure on the FDA. Shneider even described federal interventions as people "putting their foot [on] the neck of the FDA. "

He also acknowledged that Jaci's case would likely provide a roadmap for physicians hoping their patients would receive preclinical treatment, just as his Columbia team relied heavily on the experience of Dr. Timothy Yu, who had point a similar process to obtain an experimental drug. for Batten illness to a patient last year.

Nevertheless, he hopes that congressional pressure is not a lasting lesson of his business.

"I do not know how sensitive the FDA is to Congressional pressure, I honestly hope it is not too much. They have a job to do, "said Shneider, adding that he did not know about Bill King before it was tabled.

After STAT published this article, an FDA spokesperson said the agency regularly received extensive access requests from "doctors, patients, family members, and others, including members." Congress on behalf of the electorate ", and that" each application is dealt with individually, regardless of the route chosen. " entrance, and is approached with the same attention and the same rigor. "

The ethical quagmire of Jaci's affair is all the more complicated as the Hermstads are trying to raise $ 700,000 to pay for the treatment.

Shneider stated that this money was used to "perform the basic tasks" required for Jaci's treatment, such as paying a contract research organization for the remaining tests needed for the drug, as well as the cost of infusions, hospitalizations, and Jaci's displacements. in Columbia.

"I do not have and I should not use the resources of my center for a patient like this. It does not affect others. So I did not have the money to pay for it. The financial burden will be largely borne by the family and the community, "explained Shneider.

While a drug manufacturer was involved in developing the drug, none of the funds will go to this company, which "has nothing to do with it, yet," according to Shneider. Shneider declined to name the company involved, which appears to be Ionis Pharmaceuticals.

"When they were contacted by scientists and doctors looking for a potential treatment against Jaci, we answered them yes, by providing some of our early research on oligonucleotides. … We also continue to advise them on antisense technology and its use in the treatment of ALS, "said Frank Bennett, senior vice president of research and head of the franchise for neurological programs at Ionis, in a statement.

Even if the money collected by the family is not going to cover the pockets of a drug manufacturer, Fernandez Lynch of the University of Pennsylvania said funding for this treatment "raises a ton of ethical problems."

"What about other patients who can not afford this type of access and who do not have that kind of political weight? Should people contribute to a GoFundMe that is extremely unlikely to generate profits? What do we do for patients when we develop this spirit of fighting the disease at all costs? She asked.

FAs for the Hermstads, Jaci's treatment is much less a philosophical debate about the separation of powers or the financing of health care than the importance of continuing to try.

Their story with ALS begins in 2005, long before the national slogan was invoked, or even if Jaci was diagnosed with the disease, when Jaci's twin sister, Alex, was diagnosed with the same form of ALS that caused her to develop. now forces to fight his life, a rare mutation known as FUS P525L.

The fear that Jaci, too, has the mutation, has always been behind the heads of the Hermstads, but these fears only reached their peak last November, when Jaci began to experience symptoms such as back pain and difficulty walking long distances.

Then came Valentine's Day 2019. A snowstorm overcame the Iowa highway, turning the tense three-hour drive led by Jaci's doctor into a precarious six-hour hike. And it got worse when Jaci received the news she had been dreading from the beginning: she too had the same rare and almost certainly fatal form of ALS that had killed her twin sister.

Lori Hermstad, Jaci's mother, describes it as the worst day of her life, just after Valentine's Day 2011: the day she buried Alex.

"You can not explain the emotional pain," said Lori Hermstad. "It's the worst sort of grief anyone can describe."

Since then, ALS has continued to zap Jaci's nerve cells.

"I do it for a living and I tell you, it's striking, the case of its decline," said Shneider.

A few months after her diagnosis, she could no longer ride on her beloved horse, Bud, and she had to think seriously about getting her under a fan.

"Knowing that you have your last child alive and that it is actually possible that this is a breakthrough and that it is too late is another type of torture that you can not even describe", said Lori Hermstad STAT.

The Hermstads met with the King representative on the occasion of a profit for Jaci in March. The two got along well, even getting ready to work together to open an arena of horses when Jaci feels new again.

And after they met each other, contacting him was a bit like contacting another friend or family member. They did and do everything they can to fight for Jaci.

"He has been a great support and advocate and we are so grateful to have done all he has done to help Jaci," said Lori Hermstad.

And Lori, at least, insists that any family should be allowed to do the same, regardless of the political environment.

"There should be absolutely nothing, no bureaucracy, nothing, to prevent the FDA from allowing anyone who is going to die to not try a drug. Period, she says.

For the most part, the debate does not worry the Hermstads. They are busy coping with the daily challenges associated with advanced ALS, such as Jaci's increasingly serious breathing problems. And they have not finished pushing. Their new campaign is closer to home: they hope that Jaci can get treatment from his appointment scheduled June 10.

"Until that happens, I think it 's the moment we can really celebrate, because a lot of things can happen two weeks from now," said Lori Hermstad. "It's still scary."