Considering medicine through the eyes of Agustin Fernandez is a rollercoaster of emotions: disbelief, incredulity, agreement, skepticism, and more.
In a past life, Fernandez was an Oscar-winning producer with no experience in medicine — aside from a few investment deals. He is now CEO of Springfield, Illinois-based Rational Vaccines, a company developing what he says could be a “functional cure” for genital herpes, meaning patients could be symptom-free.
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With his outsider status, Fernandez rejects the established path for proving drug safety and efficacy. It’s an approach that he defends with references to compassionate use, drug pricing, approval speed and patient autonomy.
In other words, it’s a case study for what some proposed FDA deregulation could look like.
As that debate picks up steam in Washington, Rational Vaccines is fast-tracking its live attenuated vaccine for the herpes simplex virus (HSV) to the market — wherever that may be. Enrollment will soon begin for trials in Mexico and the Caribbean, following a single Phase 1 study of 20 patients in the Federation of St. Kitts & Nevis.
“Mexico has about a four-to-five year window for sales if the trials go as we think they’ll go,” Fernandez said in a recent phone interview. “We’re doing trials in the Caribbean as well and we’ve been approved for sale in a couple of jurisdictions in the Caribbean.”
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
The move is less about rebelling against the FDA and more about getting to patients as soon as possible, Fernandez said. The U.S. won’t be ignored, but it’s a much longer path-to-market.
“We’re clearly pushing forward on all tracks,” he explained. “What we’re not going to do is wait for the U.S. That’s the strategy that is mistaken and that causes a lot of companies to not even look at this.”
The U.S. represents just a fraction of the world’s population and it makes sense from a business standpoint to start in areas with less regulation, he said. The thinking is that the company can build a pipeline and create revenue in just a few years, working up to the expensive FDA approval process.
Ethical debates aside, there are looming scientific questions. Is a functional cure for this infection worth the potential risks? And can this vaccine deliver on the claims?
An unmet need
There are two major strains of the herpes simplex virus, HSV-1 (typically associated with cold sores) and HSV-2. The World Health Organization estimates that some 11 percent or 417 million people between the ages 15-49 worldwide are infected with the latter.
Most HSV-2 infections are asymptomatic. When symptoms do strike, they typically include genital ulcers, fever, body aches, and swollen lymph nodes. In more severe cases a condition known as postherpetic neuralgia can present, inflicting a shingles-like nerve pain throughout the body.
Transmission of the HSV-2 virus to newborns during childbirth is a serious national and global concern. As is the increased risk of contracting HIV.
Despite the global burden of disease, genital herpes has proven very difficult to treat. Antiviral medications are used to suppress symptom outbreaks but there not always effective. Even when symptoms subside, the virus can lay dormant in nerve cells for years.
Attempts to create a prophylactic or therapeutic vaccine for HSV hark back to the 1930s. All have failed. Out of concerns for safety, most have taken what is known as a subunit approach, introducing isolated fragments of the virus to safely stimulate an immune response.
Toxicity is low, but efficacy has also been absent.
For over a decade, William Halford, an associate professor at Southern Illinois University’s School of Medicine, focused his research on live HSV-1 and HSV-2 vaccines. These vaccines retained 99 percent of the antigens present in the infectious strain but with some small tweaks, they established a track-record of safety in pre-clinical studies.
Rational Vaccines
Fernandez said he began to explore the field several years ago after witnessing friends and family suffer in silence.
It was frustrating. Subunit vaccines hadn’t proven successful, but companies in the United States kept trying and trying, he said, hoping that a small piece of the virus would be enough to elicit a robust immune response.
Eventually, Fernandez stumbled upon Halford’s research.
“I sort of devoured everything in the space and Dr. Halford’s science is the only one that really made sense, that had a real shot of succeeding,” he recalled.
The pair connected and over time, Fernandez convinced Halford to commercialize his work. On its website, Rational Vaccines claims its live HSV-2 ICP0– mutant vaccines have been shown to be up to 100 times more protective against HSV-2 genital herpes than HSV-2 subunit vaccines.
If the science was so apparent to an untrained eye, why has it taken this long to develop an effective live vaccine?
“When you ask me what I think, that’s a Pandora’s box sort of question,” Fernandez said. “If you ask me why they’re still doing that [testing subunit vaccines] and not approving a live viral vaccine for HSV, which Dr. Halford has already created, I would point to the fact that the largest subunit [program] that ran for about 12 years, maybe they spent a billion dollars on it, it was funded by a company called GlaxoSmithKline. And it’s just really funny that as they’ve been pushing this approach that just keeps failing over and over again, they’ve been able to sell antiviral drugs to the tune of $4 billion each year.”
The herpes simplex virus market is now approaching $4.8 billion per year, though the revenue is split across many companies — not just GlaxoSmithKline (GSK). A spokeswoman from GSK declined a request for comment.
Risk and reward
There is a high-bar for safety in vaccines, as they are typically prophylactic and administered to millions of healthy patients.
Despite the vaccine classification, Rational Vaccines’ Theravax HSV-2 is being tested as a therapy for patients already infected with the virus and suffering from the most severe outbreaks. Patients who are struggling with the disease may believe the risk is worth the reward.
“We really selected for the most acute sufferers of herpes; people that have 12 or more outbreaks a year, that have antiviral resistant strains and suffer from herpetic neuralgia,” Fernandez said.
He thinks of it as an immunotherapy that may require several booster shots. In the phase 1 study, 65 percent of patients achieved complete remission and 20 percent had a partial remission. Fernandez is anxious to bring these results to millions of patients worldwide.
The enthusiasm seems to run both ways.
Genital herpes remains a very stigmatized and silently debilitating condition. There are no celebrity advocates or vocal public movements, the discussion lives online and it’s mostly anonymous.
With news of Rational Vaccines’ phase 1 trial, patients have rallied. Over 1,000 people have signed this petition for Halford to speak before Congress and underscore the immense burden of herpetic diseases.
If TheravaxHSV-2 is effective, should those patients have to wait up to a decade to see the benefits?
“The idea is that you can serve these markets and treat people who really need it badly and then work your way back to the FDA,” Fernandez stated. “For humanitarian purposes, I think it makes perfect sense. Whoever is willing to treat their citizens then we’re willing to help.”
Controlling expectations
The problem is, there’s no way to know if it does work as advertised. Noone, Fernandez and Halford included, can categorically prove that it’s safe. There are so many false promises in this field, some misguided, some exploitive.
In a statement presenting its Phase 1 data, Rational Vaccines described “groundbreaking results” from a study of a “potentially revolutionary” vaccine.
Along with monitoring safety and efficacy, the FDA — directly and indirectly — controls what scientific claims are made. Companies developing therapies are typically conservative until the drug’s value has been thoroughly proven. At that point, their marketing language will be thoroughly scrutinized.
As Rational Vaccines charges ahead without the guidance of the FDA, many patients are being swept up with the promise of an unbridled breakthrough.
Here’s CBS New York reiterating the early sensational claims:
[youtube https://www.youtube.com/watch?v=TP_6X7GxJbg]
It’s an emotionally charged issue. As deregulation will surely be.
Photo: Big Stock
