Sanofi is the largest company devoted entirely to vaccines and is currently running a Phase I/II clinical trial on 6 different formulations of HSV529, G103, and an adjuvant.
HSV529 is a replication-defective vaccine while G103 is a subunit vaccine. In a Phase I trial completed in 2018, HSV529 induced a statistically significant increase in antibody titers for participants who were both positive and negative for HSV.
In a preclinical trial in guinea pigs in 2016, G103 was able to effectively reduce both symptoms and shedding by 50%.
The current Phase I/II clinical trial is looking at different combinations and formulations of HSV529, G103, and an adjuvant in order to find the optimal dose in eliminating outbreaks and shedding.
Phase I completed in May 2021 and Sanofi has a estimated completion date for Phase II in May 2024. This suggests Phase I has shown safety/potential efficacy and recruitment for Phase II is estimated to start end of 2022.
Excision Bio has illustrated the possibility in developing a curative gene therapy using CRISPR in treating both active and latent HSV infection in the body. The company has stated that they plan to begin clinical trials in Q1 2023.
Excision’s cutting edge CRISPR gene therapy platform is built on technology licensed from the Doudna Lab at UC Berkeley and the Khalili Lab at Temple University. They are the first company to remove HIV genomes from animals and generate functional cures for HIV.
The company’s primary focus at this point in time being curing HIV with CRISPR. The company is in the middle of filing their IND with the FDA for HIV clinical trials, which they plan to begin in 2021.
In February 2021 Excision announced $60 million raised in funding to focus on their research streams including HSV.
The most frequently asked question in our community?
What is the timeline for a Herpes Cure?
When will there be a herpes cure? There have always been companies working towards better treatments, vaccines, and cures for HSV-1 and HSV-2, and many have failed. But recently two events changed the possible timeline for a Herpes cure significantly:
In 2012, CRISPR was discovered by a group of scientists, namely Dr. Jennifer Doudna. CRISPR reduced the time and cost in gene editing by over 99%. Only 5 years later, the FDA approved the first gene therapy on the market called Luxturna, which partially cures a rare, but horrible eye disease that results in blindness. Today, we now have 3 organizations (Shanghai BDgene, Excision BioTherapeutics, and Fred Hutch Cancer Research Center) using gene editing to actually cure Herpes Simplex Virus.
In 2017, the therapeutic vaccine for herpes zoster, Shingrix, was approved by the FDA unanimously. This vaccine was significant in a number of ways. Firstly, it has the highest efficacy rating out of any therapeutic vaccine ever developed with a 91-97% efficacy in preventing zoster outbreaks for over 4.5 years after one 2-dose regiment. Secondly, the vaccine is a subunit vaccine, which typically are not as effective for therapeutic applications. However, the reason Shingrix in particular is a highly effective subunit vaccine was due to the adjuvant used. An adjuvant assists in boosting the immune response to a virus.
This why Shingrix is much more effective than the previous therapeutic vaccine for herpes zoster, Zostavax, which is live-attenuated and only has a 50-60% efficacy. The Sanofi Pasteur trials, for example, are utilizing an adjuvant for their 4 vaccines being tested for Herpes Simplex Virus, HSV-2.
Given these two developments in the past 10 years, it is only a matter of time before an effective therapeutic herpes cure, vaccine or gene therapy is released on the market. In terms of when exactly, either one will make it to market is harder to say.
If we look at how long the Shingrix vaccine was in trials, it lasted from Phase I in 2008 to FDA approval in 2017, so a total of 9 years. If the Sanofi Pasteur trials follow a similar trend, we’ll see their HSV-2 therapeutic vaccine on the market around 2029. In email communication with X-Vax last year, they indicated plans to begin Herpes cure clinical trials in 2022 and anticipated that trials will last about 7-10 years before being released on the market, so assuming 7-10 years from Phase I to market is reasonable.
The closest new treatments coming to market, however, would be a monoclonal antibody treatment (from either Heidelberg Therapeutics or United BioPharma both of which are in Phase 2 trials), 2nd a new more effective antiviral Pritelivir from AiCuris (currently in Phase 3 trials), or 3rd a new immunotherapy SADBE from Squarex (currently planned for Phase 3). All of which are estimated to hit the market in 2025.
Time flies, so we have to both be patient and advocate for a Herpes cure urgently.
The reason Herpes Cure Advocacy was born, the Herpes Simplex Virus cure research at the Jerome Lab at Fred Hutch Cancer Center provides great hope.
Research at The Jerome Lab is on a sterilizing cure, developing a gene therapy to fully eradicate HSV-1 and HSV-2. So far, Dr. Keith Jerome and team has removed over 95%of latent HSV-1 in mice, effectively curing the disease since the remaining 5% of the latent virus remained inactivated.
Dr Jerome has now begun similar work to cure guinea pigs with a personal goal to start human clinical trials in late 2023. The ultimate goal as stated by him is to eradicate 100% of HSV-1 and HSV-2 in the body in a one-and-done treatment.
Guinea pig testing is underway and results are expected Q1 2022. Latest detailed overview of his gene editing approach to curing HSV by Dr Jerome. Also, a January 2021 Q&A update on with Dr. Jerome is here.
We asked our community two questions. How has HSV affected your life? And what would better treatment or a cure mean for you?
How has HSV affected your life? I was diagnosed with HSV-2 at 21. The doctor was very abrupt and offered no support, medically or emotionally. It was, quite literally, soul crushing. I’d been with my boyfriend 3 or 4 months at the time and made him get tested. Negative. Looking back, it’s clear that he is an asymptomatic carrier who got a false negative because he wasn’t actively shedding anymore when he was tested. In the years since I’ve also been exposed to HSV-1. As I’ve aged I’ve found my symptoms have worsened and I’ve been on antivirals to mediocre success for nearly a decade.
That’s what helps me hang on and gives me hope.
I’ve had two kids during this time and motherhood increases the transmission anxiety to the point of obsessive behaviors and occasional suicidal thoughts. I am never not worried about my children. We discourage sharing drinks, food, utensils, and cups, we encourage thorough hand washing, and I never kiss them. I can’t kiss booboos like other moms. The skin on my hands is reptilian from my constant hand washing. The stigma around the virus means I have no one to talk to about it, save my partner. My physical symptoms are, luckily, more annoying than anything else, but the mental and emotional toll is excruciating. Having contracted it from someone who is asymptomatic, the fear that I’ll transmit it during asymptomatic shedding is constant. This is why I don’t ever kiss my children. If it weren’t for Herpes Cure Research group I’ve found and their proactive work towards awareness and supporting cure research I would be a hopeless, anxious mess.
What would better treatment or a cure mean for you?
If there was something that could stop the shedding and reduce or remove my chances of transmission it would be a life saver. My biggest fear is giving this to someone who might have more extreme physical symptoms than I do. If I have to deal with my own physical symptoms and risks forever, so be it, but knowing that I could no longer transmit anymore would mean I could kiss my kids. I would do anything for that, risk anything. The timeline for treatments is long and chances are that when/if anything is available my kids will be teens or maybe even adults. I’m in my early 30s and my hope is for something that will let me kiss my grandkids. That’s what helps me hang on and gives me hope.
Why don’t we test for herpes in a standard STI panel? We explore this rationale below.
How do you protect a population from an infectious disease? You test for it and you track it.
Current CDC recommendations for Herpes Simplex Virus (HSV-1 and HSV-2) surveillance and testing fail to protect the public from transmission. With 85% of HSV+ people unaware of their status and the majority of transmission from asymptomatic carriers, CDC failure to test creates a loop hole for transmission. What else, aside from preventative and diagnostic testing, is more important?
Additionally, when patients are not explicitly told they aren’t being tested for Herpes providers do not have informed consent. This means even when a sexually active individual is proactive about their sexual health and has standard STI testing, they will not be tested for Herpes Simplex Virus and they are not told Herpes is not included. Meaning they can be HSV+, could be transmitting to multiple partners, and not know it.
Is ignorance bliss?
In the US, the CDC guidelines are based on guidance from the United States Preventative Services Task Force (USPSTF). Read the rationale here.
Here are the key issues they have given for not including HSV-1 or HSV-2 in standard STI testing:
COST: The rebuttal to this is all medical care is voluntary. We don’t not provide an MRI because of cost!
INACCURATE SEROLOGY TESTS: The rebuttal to this is to implement a two-step testing with Western Blot.
PSYCHOLOGICAL BURDEN OF FALSE POSITIVE: We believe that benefit of many outweighs the burden of the few. If 85% of carriers are unaware of their status this creates a loophole for asymptomatic spread. Reduction of transmission, and protection of sexual health, is more important to promote than it is to preserve a carriers ignorance.
POST-DIAGNOSIS BEHAVIOR WONT CHANGE: This a clear double standard with CDC guidelines for STI testing. By promoting ignorance of HSV+ status, you create a loophole for asymptomatic spread from the 85% who are unaware of their status – a dynamic that comprehensive testing could help curtail.
Herpes Activism Opportunity
Email the USPTSF! Tell them their rationale for not testing is paternalistic and based on bias. People have a right to know what they have and be protected from others who do not know what they have. A sample email is here.