Tagged Clinical Trials

Desperate Quest For Herpes Cure Launched ‘Rogue’ Trial

As 20 Americans and Brits flew to a Caribbean island for a controversial herpes vaccine trial, many of them knew there were risks.

The lead U.S. researcher, William Halford, openly acknowledged he was flouting Food and Drug Administration regulations in the consent forms they signed. He would be injecting them with a live, though weakened, herpes virus without U.S. safety oversight.

Still, many of them felt upbeat when they arrived on St. Kitts and Nevis in the spring of 2016. They had struggled for years with debilitating, painful herpes. Halford, the creator of the vaccine, sounded confident.

Maybe they could be cured.

“It felt like paradise,” one of the participants recalled. “Or therapy combined with vacation.”

A year later, their optimism has turned to uncertainty. Memories of kicking back in a Caribbean hotel during the trial have been overshadowed by the dread of side effects and renewed outbreaks.

But they can’t turn to Halford, a Southern Illinois University professor. He died of cancer in June.

They also can’t rely on his university, which shares in the vaccine’s patent but says it was unaware of the trial until after it was over. Because the FDA didn’t monitor the research, it can’t provide guidance. Indeed, there is little independent information about what was in the vaccine or even where it was manufactured, since Halford created it himself.

At a time when the Trump administration is pushing to speed drug development, the saga of the St. Kitts trial underscores the troubling risks of ambitious researchers making their own rules without conventional oversight.

“This is exactly the problem with the way the trial was conducted,” said Jonathan Zenilman, an expert on sexually transmitted diseases at Johns Hopkins Bayview Medical Center in Baltimore. “These people are supposed to have rights as human subjects, but now there’s nowhere for them to go. We may never know if this vaccine worked, didn’t work or, even worse, harmed anyone.”

Rational Vaccines, the U.S. company co-founded by Halford, still hopes to market the vaccine. It touted success online and to other researchers, prompting millions of dollars of recent investment, including from a company run by Peter Thiel, a backer of President Donald Trump.

Thiel, a PayPal co-founder who has excoriated the FDA as too bureaucratic, declined to answer questions about his investment, which occurred after the trial had ended.

Kaiser Health News interviewed five of the 20 participants in the clinical trial and several associates of Halford.

The participants agreed to speak on condition of anonymity because they don’t want to be known as having herpes. Most also said they feared retaliation from Halford’s company but hoped by speaking out some of their concerns might be addressed.

Their accounts, along with documents, a video and emails obtained by KHN from the offshore trial, pointed to what experts said were serious irregularities:

  • Halford did not rely on an institutional review board, or an “IRB,” which monitors the safety of research trials.
  • The company has said it doesn’t know where Halford manufactured the vaccine, so it isn’t known whether he followed U.S. government guidelines when transporting it.
  • Halford offered booster shots of the unapproved vaccine inside the United States. FDA regulations prohibit such injections.
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“The FDA goes after these types of violations,” said Holly Fernandez Lynch, a lawyer and assistant professor who specializes in medical ethics at the University of Pennsylvania’s Perelman School of Medicine. “[Researchers] can be prosecuted.”

SIU, however, did little to discourage Halford. The university, which has a financial interest in the patent, said it learned of “the concerns” only after his death. In August, after KHN asked about the trial, the medical school’s IRB launched an investigation into whether Halford violated U.S. regulations or university rules.

In a statement to KHN, Rational Vaccines acknowledged that Halford “discussed a myriad of concerns … including the potential need for booster shots.”

“Unfortunately, Dr. Halford is no longer with us to address all the ways in which he may have investigated his concerns …,” stated the company. It added, “We nevertheless wholeheartedly intend to continue his line of investigation in a clinical setting to international good clinical practice standards.”

Racing Against Time

Halford first broke with scientific protocols in 2011, shortly after he was diagnosed with nasal cancer and treated with chemotherapy and radiation, according to an account he later posted on his blog.

By then, Halford was in his 40s and had worked almost a decade at SIU’s School of Medicine.

Halford, who did not have herpes, realized his cancer might not give him much time. If he submitted to the FDA’s oversight, it would take years, he reasoned in his account.

He decided to become his own research subject, injecting himself more than two dozen times with the vaccine.

“There is an ongoing herpes pandemic that demands the scientific community’s attention today, not tomorrow,” he wrote in his blog, which by his count received thousands of hits.

The experiments on himself, Halford believed, demonstrated the vaccine was safe.

In 2015, Halford set his sights on launching an offshore clinical trial.

However, his unorthodox approach made some of his peers recoil.

“He sat in my kitchen and tried to convince me to join him,” said Terri Warren, a nurse practitioner in Oregon who was approached by Halford in 2016 to help with the trial. “He believed so firmly in his vaccine. He said, ‘Think of all of the herpes patients who are suffering.’”

Warren had previously worked with Halford on a different, IRB-approved trial studying a new blood test to diagnose herpes. This time, she said, she became concerned about his methods, including how he was selecting his participants.

“I told him absolutely not,” she recalled. “I didn’t want anything to do with it. I felt bad for him because he was dying, but I thought he had lost perspective.”

But Halford did find backers, including Hollywood filmmaker Agustín Fernández III, whose credits include action films and an award-winning documentary.

Fernández recently declined to respond to questions. But in an earlier interview this year with KHN, he said he initially contacted Halford to try to help someone he knew who was battling the disease. He said he didn’t have herpes, or a background in science.

Fernández, however, became such a believer in Halford, he said, he allowed Halford to inject him with the vaccine. In 2015, he co-founded Rational Vaccines with Halford and invested his own money into the company. That same year, the company licensed two patents related to the vaccine from SIU.

“I felt like Bill had the answer, and we had to make sure he got a chance to prove it,” Fernández said.

‘Finally … Someone Who Cared’

As soon as news began spreading in the tight-knit herpes online community that Halford may have a cure, he began hearing from the most desperate who asked to be included in any future research.

For many, herpes is a mild disease that can be controlled by antiviral medicines. However, for some, it becomes a life-altering disease that destroys any hope of intimate relationships.

To several of the participants, Halford was an empathetic scientist who refused to give up on finding a cure.

“After dealing with doctors who had no answers, it felt like you were finally talking to someone who cared and could help,” said a participant in his 30s from the South who had described the trial as “paradise.”

There were other perks as well.

Rational Vaccines told some participants they would be reimbursed for their flight and hotel expenses. If they got through the entire trial, they would be given an extra $500.

As Halford organized two groups of 10 participants, he instructed them on drawing their own blood for the trial, according to a video filmed in a medical lab.

He proceeded with the trial from April to August 2016, giving participants three shots over three months.

Once in St. Kitts, many of them quickly bonded with one another and Halford. Even though they ranged in age from their 20s to 40s and came from different regions, they had the disease in common. They commiserated about how herpes had wreaked havoc on their lives.

“It was a relief to meet people who understood what we were talking about,” the Southerner said.

But other participants now say they noticed some troubling signs.

They received the injection in a house in St. Kitts, not a medical clinic.

Halford, whose gaunt frame made his cancer apparent by then, at times appeared disoriented.

Fernández, a constant presence, was introduced to them by name and made some of them uncomfortable when they socialized over drinks and dinner.

Some patients became anxious about their participation soon after receiving the vaccine.

One, a web developer in his 20s, felt ill after receiving just one dose.

“I experienced tiredness and ringing in my ears,” said the web developer, who reported the feelings along with “disequilibrium and slurred speech” continue to this day.

He said he decided not to return to St. Kitts for follow-up shots after Halford dismissed his symptoms as arising from a common cold.

Another participant, a Colorado woman in her 40s, said she told Halford she experienced flu-like aches and pains and tingling and numbness soon after the second shot. The symptoms were followed by an “excruciating” 30-day outbreak of herpes.

“I have new symptoms every day,” that woman later wrote Halford in an email exchange provided to KHN. “This is terrifying.”

Halford initially dismissed her symptoms, speculating they were caused by a mosquito-borne virus, she said.

She returned for the third shot but had her doubts. Halford and Fernández met her at a café to talk about her concerns, she recalled.

“[Fernández] kept saying, ‘You signed the consent form. You knew the risks,’” said the Colorado woman, who said Halford then removed her from the trial.

Another participant, a Californian in his 30s, said he went through with all three shots despite feeling a “terrible pain in my stomach.”

Halford then told him he had noticed in his research of mice that another version of the virus entered the gut of the mice and killed them, the participant said.

“I then thought maybe this is dangerous,” said the Californian, whose pain went away but his outbreaks did not.

Warren, the nurse practitioner in Oregon, said two participants tracked her down as a herpes expert. She said that they described possible side effects from the vaccine.

Halford had told participants he would follow up on their reactions to the vaccine for a year, according to the consent form. But he stopped sending questionnaires to the two participants who said they had been dropped from the trial.

Warren said that even when researchers stop administering a vaccine because of possible side effects, known as adverse events, they have a duty to track the subjects’ reactions.

“There is no doubt that these were adverse events that should have been reported,” Warren said.

Rational Vaccines did not respond to questions about the complaints. In previous public statements, it acknowledged that one of the 20 participants was concerned about possible side effects.

Some participants also wonder where Halford made the vaccine and how he transported it to St. Kitts.

Halford told his business partner he had made it outside of the United States, without disclosing where.

After the trial ended, some participants began complaining that the vaccine hadn’t worked. Halford and Fernández offered booster shots, according to four participants.

One participant, a man in his 40s who was also from California, declined to get the booster. He said he decided to go back to antiviral drugs when his outbreaks returned.

The Southerner said he agreed to allow Halford to give him booster shots at an office in Springfield, Ill., where Halford worked.

“It was between me and him,” said the participant. “He was doing me a favor.”

“I don’t know if it was a different strain or what, but he gave me a set of double boosters at the same time, one in each leg,” recalled the Southerner, who said he didn’t have records of the injections. He said he received them as Halford continued to collect data for the trial.

Months later, he said, he returned a second time for another set of boosters.

Courting Support Without Results

Halford, meanwhile, tried to persuade a U.S. scientific journal to publish a lengthy manuscript detailing the results of both his experiments on himself and his offshore trial. Halford put the cover letter on SIU letterhead.

In December 2016, only months after the trial had ended, Halford’s paper was rejected by the journal.

“This manuscript is partly a vision, partly science, and partly wishful thinking …,” said one reviewer for the journal. “Neither safety nor efficacy has been demonstrated by the data presented.”

Halford asked his former doctoral adviser, Daniel Carr, to attend a Rational Vaccines advisory board meeting. Carr, a University of Oklahoma Health Services Center professor, said he and other invitees heard glowing reports about the trial.

Carr agreed in May to present the trial data at a conference of herpes experts in Colorado.

A published summary of the event listed Carr as a lead author, though he said he wasn’t involved in the research.

“I just did it to help him out,” said Carr, who asked for his university’s permission to be on Rational Vaccines’ advisory board and is waiting for word on federal funding to study another version of Halford’s vaccine. “I also presented it because I thought that the scientific community would find it interesting.”

Despite its patent agreement reached in 2015, SIU said it was in the dark about Halford’s offshore activities until October 2016 — months after the trial had ended.

Halford, meanwhile, promoted his work at events attended by university officials.

In October 2016, Halford was a keynote speaker at an SIU-sponsored technology and innovation event to discuss his vaccine work.

Then, in April 2017, Halford and Rational Vaccines held a press conference to trumpet an investment pledge by Thiel’s company, according to materials handed out at the event. University officials, including SIU’s medical school dean, were invited speakers.

The university’s IRB is continuing its investigation, which includes scrutinizing whether Halford used university resources.

“If there are areas of concern, SIU will report those findings promptly to Department of Health and Human Services,” said SIU spokeswoman Karen Carlson. “We will also communicate our findings with the scientific community and the public.”

FDA spokeswoman Lauren Smith Dyer declined to comment on the trial except to say the FDA does not have jurisdiction over offshore trials that don’t seek agency approval.

Dyer, however, added that the export from the United States of an unapproved vaccine for research use and the injection of it on U.S. soil would be within the agency’s jurisdiction.

Even so, some participants don’t regret taking part in the trial.

“When you feel like a disease has ruined your life, you become desperate,” said the Southerner, who believes the boosters have lessened his outbreaks. “Some people contemplate suicide. You’re willing to do almost anything.”

Other participants still hope for some sort of accountability.

“I feel like without a doubt that my symptoms were vaccine-related,” said the Colorado woman. “I feel like it triggered something that I’ll have for the rest of my life.”

No matter what, experts said, the university has a responsibility to conduct an in-depth investigation. So far, the university has not reached out to participants who spoke to KHN.

“This researcher went rogue,” said Fernandez Lynch, the lawyer who specializes in medical ethics. “It’s true that universities can’t stand behind their researchers watching their every move. But when one of their own goes rogue, a university should launch an aggressive investigation, interview the participants and make sure it never happens again.”

KHN’s coverage of end-of-life and serious illness issues is supported by The Gordon and Betty Moore Foundation and its coverage related to aging & improving care of older adults is supported by The John A. Hartford Foundation.

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Pursuing the Dream of Healthy Aging

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Credit Paul Rogers

Given their druthers, most people would opt for a long and healthy life. Few relish the idea of spending years, even decades, incapacitated by illness, dependent on caregivers and unable to enjoy the people, places and activities that make life worth living.

In 1980, Dr. James F. Fries, a Stanford University physician who studied chronic disease and aging, proposed that a “compression of morbidity” would enable most people to remain healthy until a certain age, perhaps 85, then die naturally or after only a brief illness.

Now, a prescient group of experts on aging envisions a route to realizing Dr. Fries’s proposal: one or more drugs that can slow the rate of aging and the development of the costly, debilitating chronic ailments that typically accompany it. If successful, not only would their approach make healthy longevity a reality for many more people, but it could also save money. They say that even a 20 percent cut in how fast people age could save more than $7 trillion over the next half-century in the United States alone.

“Aging is by far the best predictor of whether people will develop a chronic disease like atherosclerotic heart disease, stroke, cancer, dementia or osteoarthritis,” Dr. James L. Kirkland, director of the Kogod Center on Aging at the Mayo Clinic, said in an interview. “Aging way outstrips all other risk factors.”

He and fellow researchers, who call themselves “geroscientists,” are hardly hucksters hawking magic elixirs to extend life. Rather, they are university scientists joined together by the American Federation for Aging Research to promote a new approach to healthier aging, which may — or may not — be accompanied by a longer life. They plan to test one or more substances that have already been studied in animals, and which show initial promise in people, in hopes of finding one that will keep more of us healthier longer.

As Dr. Kirkland wrote in a new book, “Aging: The Longevity Dividend”: “By targeting fundamental aging processes, it may be possible to delay, prevent, alleviate or treat the major age-related chronic disorders as a group instead of one at a time.”

His colleague S. Jay Olshansky, a gerontology specialist in the School of Public Health at the University of Illinois in Chicago, said it is often counterproductive to treat one disease at a time. Preventing cardiac death, for example, can leave a person vulnerable to cancer or dementia, he explained.

A better approach, Dr. Kirkland said, would be to target the processes fundamental to aging that underlie all age-related chronic diseases: chronic low-grade inflammation unrelated to infection; cellular degradation; damage to major molecules like DNA, proteins and sugars; and failure of stem cells and other progenitor cells to function properly.

The team, which includes Dr. Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in The Bronx, and Steven N. Austad, who heads the biology department at the University of Alabama at Birmingham, plans to study one promising compound, a generic drug called metformin already widely used in people with Type 2 diabetes. They will test the drug in a placebo-controlled trial involving 3,000 elderly people to see if it will delay the development or progression of a variety of age-related ailments, including heart disease, cancer and dementia. Their job now is to raise the $50 million or so needed to conduct the study for the five years they expect it will take to determine whether the concept has merit.

The project represents a radical departure from ordinary drug studies that test treatments for single diseases. However, the group, spearheaded by Dr. Barzilai, said the Food and Drug Administration has endorsed their idea to test a single substance for effectiveness against a range of ailments.

“If metformin turns out not to work, there are several other substances in the pipeline that could be tried,” Dr. Barzilai said. “Under the auspices of the National Institute on Aging, three research centers have tested 16 substances in different animal models and got incredible results with four of them.”

Green tea, one of those tested, bestowed no health or life span benefits, despite its popularity. But the drug rapamycin, an immune modulator used following organ transplants, was most effective among those tested, Dr. Barzilai said.

The team is starting with metformin because it is a cheap oral drug — costing about two cents a pill — with six decades of safe use in people throughout the world. Among those with Type 2 diabetes who have taken it for years, there is evidence suggesting that, in addition to diabetes, it protects against cardiovascular disease, cancer and possibly cognitive impairment, Dr. Kirkland said, adding that “it targets the fundamental processes of aging, which tend to be linked.”

Dr. Barzilai said, “Our goal is to establish the principle of using a drug, or two in combination, to extend health span. The best we can expect from metformin is two or three additional years of healthy aging. But the next generation of drugs will be much more potent.”

Dr. Barzilai is already conducting a complementary study of centenarians, the results of which could identify more drugs to delay age-related diseases. He and colleagues are isolating genes that appear to keep these long-lived men and women healthy for 20 to 30 years longer than other people and shorten the length of illness at life’s end. Several studies have already found that individuals with exceptional longevity experience a compression of morbidity and spend a smaller percentage of their life being ill, Dr. Barzilai and his colleague Dr. Sofiya Milman wrote in the “Aging” book.

By analyzing the action of genes that extend health span, “it should be possible to devise drugs that mimic the genes’ effects,” he said. Two such gene-based drugs that show early promise against age-related diseases are already being tested.

But until definitive studies are completed and substances are shown to be safe as well as effective in prolonging health, Dr. Olshansky cautioned against dosing oneself prematurely with widely touted substances like resveratrol, the antioxidant found in red grapes and wine, or growth hormone.

Consumers must exercise caution, he warned, because “there’s an entire industry out there trying to market the products we’re testing before they are adequately evaluated.”

He also emphasized that taking a drug found to ward off age-related ills is not a license to abandon a healthy lifestyle. Doing so “could completely negate the benefit of a compound that slows aging,” he said.

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