Remember the anti-weight-gain herb Hoodia used by the San people of South Africa? Now, an even more exciting discovery could take the world of antidepressants such as prozac by storm. The herb, found in the same regions as Hoodia, seems to be nature’s answer to depression and anxiety. The global market is enormous but so are the legal and regulatory hurdles. Dr Sean Carey* reports.
Think of an antidepressant and the chances are that Prozac will come to mind. The drug, which has been the subject of several books, a film and a musical is undoubtedly the most famous in the category of pharmaceuticals called selective serotonin reactive inhibitors (SSRIs), which were launched with great fanfare in the late 1980s and made fortunes for the parent companies.
Today, Prozac and newer drugs such as Cymbalta and Effexor are routinely provided to around 40m patients by doctors in the US and Europe for a wide variety of mood disorders including major depression, obsessive-compulsive disorder, anxiety and severe premenstrual syndrome. But it is important to realise that these problems are not confined to those who live in the world’s advanced economies. Indeed, the World Health Organisation (WHO) calculates that around 120m people globally suffer from some sort of central nervous system (CNS) disorder, and forecasts that by 2020 depression will be the world’s second-largest health condition.
But could Zembrin®, a patented extract of the herb Sceletium tortuosum, traditionally used by the San and Khoi peoples of Southern Africa as an analgesic, antispasmodic, sedative, tonic and mood elevator, give conventional medications and existing herbal the alternatives a run for their money?
South African-born medical practitioner, ethnobotanist and natural health consultant, Dr Nigel Gericke, certainly thinks so. “So far the product trajectory of Zembrin® has been extremely satisfying,” he says. “There’s no doubt that it has global potential – it could be a blockbuster if clinical trials demonstrate the efficacy we see reported anecdotally.”
He claims that in the US alone nearly 21m adults aged 18 and older have some sort of mood disorder: “Antidepressants and anti-anxiety medications were prescribed more than 250m times in 2009. The total mood market in US is worth $26bn.”
Interestingly, dietary supplement products, including botanical products, currently make up only 2% of the US mood market but the potential for people keen to try a ‘natural’ substance rather than a laboratory-created pharmaceutical is obvious.
“There is a huge unmet need for a safe, effective, standardised botanical supplement that is experiential,” argues Dr Gericke. “At its peak, the sales of StJohn’s Wort [Hyperium perforatum], another herb traditionally used for depression, were running at more than $230m per year. But I believe Zembrin® to be far superior because it is so fast acting – the user will feel an effect in a very short time.”
Dr Gericke is careful to emphasise that his plant-derived product Zembrin® is not intended to compete directly with pharmaceutical drugs – at least for now. “Our target market is ordinary, everyday people suffering from stress – taking Zembrin® is a much better option for people under pressure or for people who feel uncomfortable socially who self-medicate with alcohol and other substances to help cope, for example,” he says.
In the end, however, he does not rule out an eventual tie-up with a major pharmaceutical company to promote a botanical medicine. “But that will be some time in the future.”
Profound first impact
Dr Gericke reveals that he first heard about Sceletium in 1986. “I was taking a gap year travelling after my medical studies at the University of Witwatersrand and was reading a book on psychoactive plants from around the world,” he recalls. “It had a brief mention of this South African plant, Sceletium tortuosum, and although there was not a lot of detail about its effect, it was all very intriguing. I was determined to find the plant when I got back to South Africa, and see if it had any potential modern health application.”
Dr Gericke took his first dose of Sceletium in 1991. “My wife, Olga Gericke, who was specialising in psychiatry at the time, provided some very useful insights, and a small group of us, ethnobotanists, doctors and psychiatrists experimented with various doses of the herb.”
The impact of this first encounter with the herb was profound. “It was very clear that there was a dose response – low doses had a subtle effect providing a sense of serenity and at the same time sense of alertness, while excessive doses caused a transient euphoria. This made it a very interesting substance from a pharmacological point of view.”
The experiment convinced Dr Gericke that Sceletium had enormous potential. “It was apparent that with mid-range doses there was a rapid onset of action of some sort of mood elevating and anti-anxiety effect,” he recalls. “My wife also noted that the side effects from excessive doses were similar to the side effects seen with SSRIs like Prozac, which ultimately led us to confirm that some of the compounds in the plant are indeed very potent serotonin-reuptake inhibitors.”
Dr Gericke and his partner, Deon Hofmeyr established HGH Pharmaceuticals in the Johannesburg suburb of Bryanston in 2007, with backing from the well-known South African conglomerate, HL Hall and Sons. However, a considerable amount of corporate activity had already occurred. “I had set up a number of companies before this including African Natural Health in 1992, which owned all the initial intellectual property associated with Sceletium, including the first US patent,” says Dr Gericke. “All in all, Zembrin® is the culmination of nearly 20 years of experimentation, ethnobotanical research and scientific and clinical research and development.”
Modern pharmaceutical antidepressants are not without their problems, not the least of which is that even if they do work, they may take time to have a desirable effect on patients. This does not seem to be the case with Sceletium, and the laboratory research commissioned by HGH Pharmaceuticals has provided supporting evidence.
“We really wanted to understand why the plant had such a rapid onset of action, as it could not be purely due to serotonin-reuptake inhibition, which in conventional drugs and a herb like St John’s Wort typically takes time, sometimes a few weeks, to have an effect,” says Dr Gericke.
“We have looked at different isolated compounds in the plant as well as its naturally occurring chemotypes. We have discovered a novel mechanism of action for the herb, which act synergistically with the known serotonin-reuptake inhibition,” he adds.
The implication of this high science means that only very low doses of Zembrin® extract are required to alleviate stress, tension, anxiety and enhance mood. There is other good news, apparently. “We have found in our preclinical studies and Phase 1 clinical trial that not only is Zembrin® safe, but there is a very low side-effect profile,” explains Dr Gericke. “These are exciting developments. Now that the latest patent applications have been filed, we will be publishing our research over the next few months.”
HGH Pharmaceuticals is also awaiting the completion of a Phase 2 clinical trial due in April to test further the efficacy of Zembrin®. Subject to regulatory requirements, it will come to market in August. The company has already signed a marketing agreement with New Jersey-based company, PL Thomas & Co Inc, which has a long history of successfully marketing standardised botanical extracts and other dietary supplements in the North American market. HGH Pharmaceuticals is also in advanced discussions with a marketing partner so that it can target the new growth economies of lndia and China, where there is a long tradition of using herbal medicines for a variety of ailments.
Of course, Zembrin® will also be available in South Africa and is almost certain to displace many of the branded products that have become available over the last decade. “We’ve tested a lot of the Sceletium that can be bought in pharmacies and health shops, and found that it is extremely variable in quality,” notes Dr Gericke. He thinks that there is an important lesson for consumers and producers: “You can’t just grind up the herb and put it in a capsule – it needs to be standardised in terms of alkaloid content and alkaloid composition to get the desired effect.”
And what about promoting Zembrin® in rest of the continent? “We are certainly interested in other countries in Africa, but first we would like a solid foundation in the US and South Africa,” says Dr Gericke.
Europe new barrier to botanicals
Europe has traditionally been a large market for a wide variety of botanicals. However, new EU regulations due to come into force in April demand that herbs intended for medicinal use will require a licence, something that will be prohibitively expensive for many small producers and manufacturers. The new legislation will mean, for example, that commonly available Indian, Chinese and Tibetan herbal mixes will no longer be legally available to the public.
Dr Gericke is under no illusion about what this means for Zembrin®. “The regulatory barriers for a novel botanical from South Africa coming into the European market are extremely onerous,” he says. “We will definitely need an appropriate partner to assist us.”
Despite the fact that within its borders South Africa has a high level of biodiversity, an estimated 24,000 plant species, a figure surpassed only by Brazil and Indonesia, Dr Gericke reckons that there is a big lesson for other African companies working with botanicals. “We have already seen what happened with another South African herb, Hoodia gordonii, which targeted the weight-loss market,” he says, referring to the deals made by the UK-based company, Phytopharm, first with the pharmaceutical giant, Pfizer, and then with international conglomerate, Unilever, which have so far come to nothing.
“This is a great shame as around 15 years of work and a great deal of money went into product research and development. I hope that something might still come of Hoodia because Africa really needs botanicals success stories. However, without formalisation, systematisation and institutionalisation of African traditional medicine, which will need significant public funding comparable to that found in India and China, we’re not going to see the realisation of the real potential of Africa’s biodiversity and indigenous knowledge systems.”
Dr Gericke also highlights a further issue. “The regulatory barriers for novel botanical medicines in many markets are already high and are set to get higher. We are ready to go but newcomers will find it almost impossible to gain entry. Realistically, I think that the shorter-term commercial opportunities for African botanical products lie more in providing novel botanical cosmetics, functional foods, bio-pesticides, and natural flavours, fragrances and colours rather
than medicines. And partnerships with big companies with solid in-house R&D and well-established marketing like L’Oréal are probably the way to go.”
Be that as it may, Dr Gericke is justifiably proud that future profits from Zembrin® will be shared with designated San and Namaqualand communities in the Western and Northern Cape provinces. “We signed it in 2007, and is the first ever prior-informed consent benefit-sharing agreement with an indigenous community in Africa. HGH Pharmaceuticals
strives for international best practice. We have already paid three upfront tranches to the South African San Council to show good faith, and going forward, our indigenous beneficiaries will receive a generous royalty stream. It’s only right and proper that our partners in this project are properly rewarded.”
*Dr Sean Carey is research fellow in the School of Social Sciences, Roehampton University.