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When Will a Herpes Vaccine be Available?

Herpes, the gift that keeps on giving. It’s an ugly word because of the stigma associated with it, and that’s because the Herpes Simplex Virus (HSV) likes to wreak havoc with a small handful of its victims. It is categorized into type 1 (HSV-1) causing oral herpes (or cold sores) which is transmitted by skin-to-skin contact, and type 2 (HSV-2) causing genital blisters, which is transmitted sexually. The first type, HSV-1, nobody really seems to care much about, because according to the CDC, “Most people with oral herpes were infected during childhood or young adulthood from non-sexual contact with saliva.” It’s like worrying about being left-handed. The second type though, that’s the one people are scared to death of, especially when you show them scary pictures like this:

The HSV-2 virus

But should they be?

The Herpes Bible

The interesting thing about herpes is that of the people who have it, only 1 out of 10 will have noticeable symptoms which won’t be very pleasant at all. In other words, 90% of people who have genital herpes don’t know they have it unless they get tested. In order to better understand prevalence, we had one of our MBAs tuck into this 1,408-page book on the topic of Human Herpesviruses with a list price of $862 but which is selling for a cool $454 on Amazon right now (if you opt for the hardcover – and who wouldn’t). Just look at this beauty:

 It’s so jam-packed with information that in an effort to convince you to buy it, here are a small number of interesting facts contained within.

  •  Worldwide, ∼90% of people have one or both viruses (HSV-1 and/or HSV-2).
  • The rates of infection vary with country as well as levels of sexual activity
  • Developing countries bear a much higher burden of HSV-2 infection, with many populations in Africa having >50% prevalence in the general population
  • Women are at 2-to-6 fold higher risk for HSV-2 acquisition than men
  • Race, gender, and the extent to which you are promiscuous, all come into play when estimating the risk for people who live in the United States:
    • For white men, the risk is ∼10% among those who report 2 to 9 lifetime partners, and reaches 40% in those with >50 lifetime partners.
    • For white women, the risk of HSV-2 increases from about 18% among those with 2–4 lifetime partners to 35% for those with 10 to 49 lifetime partners
    • For African-American men, the risk rises from 35% in those with 2–4 lifetime partners to ∼ 50% in those reporting >50 lifetime partners.
    • For African-American women the risk increases steeply even with fewer partners, and exceeds 60% for women with more than 4 lifetime partners.

If you’re in the “Asian” or “Hispanic” market segments, we’re going to keep you in suspense. You’ll need to go buy the book to find out your odds of catching a virus that is benign in a majority of cases.

Herpes Vaccines – A $175 billion Market?

While we could go on and on with interesting facts like the ones above, there is one key takeaway here. The herpes vaccine market is massive, but complex, with multiple price points and marketing channels. If we’re to believe what the Herpes Bible says about 90% of people being infected, that’s 6.84 billion customers whom you can shame into buying your vaccine. Then there’s this little fact we’ll throw in there, also from the Herpes Bible:

  • Recent studies suggest that 20%-50% of incident episodes of genital herpes are caused by HSV-1

Excellent, so now we can argue that HSV-1 is just as bad as HSV-2 and that gives us a Total Addressable Market (TAM) of 6.84 billion people. Let’s say we give it away to 1 billion people in poor countries so everyone sees how altruistic we are, and then sell the rest at $60 a pop to half of the remaining 5.84 billion people. That’s over $175 billion in revenues on the table if we can create a herpes vaccine.

By now you probably have guessed that there’s no cure for herpes, because we don’t have a herpes vaccine yet. Sure, you can spend a bunch of money on antiviral medications and home remedies but the virus will persist by becoming latent and hiding from the immune system in the cell bodies of neurons. After the initial or primary infection, some people experience sporadic episodes of viral reactivation or outbreaks. In an outbreak, the virus in a nerve cell becomes active and is transported to the skin, where virus replication and shedding occur, causing new sores. The way HSV becomes dormant and “hides” in nerve cells is the reason why efforts to find a vaccine have been unsuccessful since the 1920s. Here’s a diagram that helps explain a herpes infection, and which happens to look like something Syd Barrett drew:

Pathway of a Herpes Infection

Credit: herpespictures.org

Problems with Herpes Vaccines

When we saw that two advanced herpes vaccine projects were halted recently, we could hardly believe that we’re that far away from curing some recurrent blisters. Massachusetts company Genocea (NASDAQ:GNCA) reached Phase II trials with promising results in reducing outbreaks and viral shedding, but confirmed it will stop spending on further research to focus on cancer vaccines. Their website still lists the GEN-003 candidate as available and ready for Stage III testing, offering to license the research to a third party. Vical from San Diego (NASDAQ:VICL) just abandoned HSV-2 trials two weeks ago after Phase II results did not prove the efficacy of their vaccine candidate.

The development of vaccines is a long and costly process, and resembles the typical drug approval process. It begins with laboratory research that usually lasts 2-4 years. At this stage, scientists are looking for the right antigens, molecules that induce an immune response against the virus in the body. This is followed by pre-clinical trials for 1-2 years where the potential vaccine is tested on cell cultures and animals to determine efficacy and safety. This also gives an idea about how best to administer the vaccine and what safe dosages look like. This is followed by three phases of clinical trials on human subjects, something that is remarkably similar to the FDA drug approval process we wrote about before. Let’s take a look at some herpes vaccines under development.

Herpes Vaccines in Development

Founded in 2011, Admedus (ASX:AHZ) is a listed medical technology company based out of Minnesota with a market cap of $53 million. Besides vaccine research, the company offers infusion systems and implantable bio-scaffolds that closely mimic the structure of human tissue for use in various cardiovascular and vascular repair applications. Their HSV-2 therapeutic vaccine (meaning it is for people already infected) candidate has passed Phase IIa in May 2017. The aim of the trial was to confirm safety, which it did successfully. According to Admedus “positive immune response to the vaccine was seen in most [of the 34] subjects”. Even the company itself wasn’t that enthusiastic about the results though, and the medical community will most likely understand more about the vaccine’s potential after Phase IIb. The team is also developing a therapeutic vaccine for the human papillomavirus (HPV), that affects about 75% of reproductive-age population in the US and is responsible for the majority of cervical cancer.

Founded in 1994, Lexington, Massachusetts company Agenus (NASDAQ:AGEN) is developing cancer immunotherapies and has a market cap of $253 million. Agenus has run a successful Phase II trial of its HerpV therapeutic vaccine candidate that ended in 2014. The trial resulted in a significant reduction of the incidence and severity of recurring outbreaks and reduced viral transmission among the 70 people who received the vaccine.

Agenus's Pipeline

Credit: Agenus

There have been no further announcements on the HerpV candidate since then, and Agenus seems to have taken it off their trial pipeline that now focuses on their immune checkpoint program for the treatment of cancers.

Founded in 1990, French company Sanofi Pasteur is the vaccines division of the multinational pharmaceutical company Sanofi, a $96 billion French pharmaceutical company. Sanofi Pasteur is the largest company in the world devoted entirely to vaccines, and manufacture vaccines for preventable diseases ranging from flu to tuberculosis and HSV-2. The company has 15,000 employees worldwide and produces more than one billion doses of vaccines per year. Manufacturing vaccines – because they contain living organisms – requires a great deal of attention and involves a production cycle of 6-36 months, 70% of which is dedicated to quality control.

Sanofi Manufacturing Process

Credit: Sanofi Pasteur

Sanofi Pasteur’s HSV-2 candidate is also a therapeutic vaccine that has passed Phase I trials successfully in 2017. The trial included 60 healthy adults aged between 18-40 years receiving three doses of the vaccine. The vaccine was safe, well tolerated, and elicited significant antibodies and modest immune responses, the study concluded.  Sanofi Pasteur is proceeding with the next stage of the trial.

Founded in 2015, Springfield, Missouri startup Rational Vaccines has raised $8.2 million from investors including Peter Thiel to develop the world’s first herpes vaccine that contains live but weakened virus strains, which could be used for both therapeutic vaccines or preventive vaccines (for people who do not have the virus). The company, founded and led by microbiologist Dr. William Halford, has conducted human trials in 2013 and 2016 allegedly without the approval of either an independent institutional review board or the Food and Drug Administration, or formal written consent from participants. It is currently being sued by three of the trial subjects for adverse side effects associated with the vaccine. Rational Vaccines did not comment on the allegations but previously confirmed will pursue FDA approval for further testing. As of now, no further information is available through official channels and their website is under construction.

Conclusions

Advanced stage projects might be failing, but interest in developing a herpes vaccine remains. The latest approach of researchers involves gene editing (otherwise known as CRISPR technology), a technology that can potentially destroy dormant HSV viruses, although several years will be needed before the technology reaches clinical trials. In the meantime, a handful of university labs and startups in early discovery and preclinical stages will hopefully keep the pipeline stocked for a product that could be sold to 6.84 billion people around the globe.

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