There hasn’t been a new hair loss drug approved in twenty years. But, a number of European companies are hot on the case, and are getting tantalizingly close to the breakthrough that is hoped for by many patients.
With body dysmorphia magnified by the omnipresent digital world, psychiatrists have increasingly linked the onset of male and female pattern baldness to mental health conditions ranging from anxiety to even depression.
Over the past decade, cosmetic surgery has looked to ease the burden. There is a scarcity of preventative treatments – the only drugs approved by regulators are Minoxidil and Propecia, both of which are only marginally effective at halting hair loss, and the former is the only treatment available to women. The value of the global hair transplant industry is therefore predicted to exceed €23B ($24.8B) by 2024.
However, hair transplants are no panacea as they can be costly and sometimes painful. As a consequence, there is a huge market for any new product that can effectively halt pattern baldness in its tracks, and a series of European biotechs view this as an opportunity. Buoyed by a number of research breakthroughs regarding the science behind hair growth, several biotechs have products in late-stage clinical trials, some of which may go on to become the first novel drug treatments for baldness in twenty years.
“The number of patients waiting for new treatment options is huge,” said Jan Alenfall, CEO of Follicum, a Swedish biotech whose lead candidate hair loss treatment is currently in phase II clinical trials.
“Transplantation is an invasive method and as such it is also associated with infections. In addition, many patients tend to require more than one transplant since the process of hair loss generally continues. Recently a lot of high-quality research from several academic groups has generated a lot of interest.”
Revisiting topical therapies
It was a research breakthrough that inspired Follicum’s development of its lead candidate drug. While studying treatments for arteriosclerosis – a thickening and hardening of the walls of the arteries that often occurs in old age – scientists at Lund University, Sweden, discovered that a variant of the protein osteopontin — a naturally occurring molecule in our bodies — could increase hair growth in mice.
Subsequent studies found that this protein variant has a very specific target on hair follicle cells and can accelerate the hair cycle from resting to growth phases. This allows it to stimulate dormant hair follicles and encourage them to start producing cosmetically visible hairs again.
So far, Follicum has tested it in an injectable form in two clinical trials, both lasting three months, in which patients reported increased hair density. Now this month, a new phase IIa trial testing a topical creamlike version of the product – thought to be more convenient for patients – is about to get underway with results expected later in 2020.
The reason why pattern baldness occurs is that hair follicles become sensitive to hormones on the scalp, most notably dihydrotestosterone (DHT), which binds to follicles and shrinks them until they no longer produce visible hair. As a result, Italian biotech Cassiopea is developing its own topical product Breezula. This treatment directly blocks the negative effect of DHT on the scalp based on a mechanism of action discovered through studying the hormone’s role in acne development.
“Our drug actually antagonizes the negative effect of DHT around the follicle, slowing down the hair loss or stopping it,” explained Diana Harbort, CEO of Cassiopea. “And those follicles that aren’t completely shut down due to DHT, they start producing hair again.”
Having already successfully completed phase II trials, and with a phase III trial planned for 2020, Breezula could become the first new treatment for male pattern baldness in the coming years, with investors already forecasting potential sales figures in the region of €350M.
Helping women with hair loss
One of the reasons why biotechs are so keen to develop topical products is because they are associated with fewer side effects. One of the major limitations of Propecia — an oral medication — is that it is associated with erectile dysfunction due to its effects on hormones in the body. In addition, because it acts systemically, it is not safe to be used in female hair loss sufferers, a patient group that has been traditionally neglected by the field.
Follicum is hopeful that its treatment could also be particularly suitable for women because it stimulates hair follicles through a completely novel process, avoiding hormonal pathways altogether.
“There are several potential advantages with a new, non-hormonal, mechanism of action,” said Alenfall. “The side effects of current therapies are not expected, and none have been seen in the clinical program performed so far. Based on this, [Follicum’s drug] might become a safe and efficacious treatment option for women as well.”
While Cassiopea’s product does act on DHT, the topical nature of the therapy means that it does not come with the safety warnings of oral drugs and studies so far suggest minimal side effects. As a result, the company is now embarking on a phase II trial of the product in female patients, which began enrolment last November.
“There are so few treatment options that actually work for hair loss, and it’s really problematic because of the cycle of social complications that really affect a patient’s self-esteem,” said Harbort. “It’s very embarrassing for them, and studies show that women are even more likely to suffer these psychological complications than men, so there’s a huge unmet need.”
Restarting hair growth from the roots
The sheer size of the hair loss market means that other companies have begun investing in early-stage research. Their aim is to try and understand more about the molecular mechanisms that underpin human hair growth and loss, with the goal of finding an entirely new class of hair drugs.
As even completely bald individuals have 100,000 hair follicles still present all over their scalp, research efforts are ongoing to try and find yet new ways of reviving these follicles, even those that have been long dormant.
Italian biotech Giuliani has been exploring one particularly innovative way of doing this. Through studying existing drugs for other conditions that cause unwanted bodily hair growth as a side effect over the past four years, it has identified completely new pathways for stimulating hair follicles.
“We have already found two or three compounds that work on these pathways and are effective at promoting human hair growth in organ culture,” said Ralf Paus, a consultant scientist for Giuliani. “The next step is to see whether they’re safe enough to topically administer them to volunteers, and then a clinical trial. If they really deliver hair growth, this will be a real breakthrough.”
While the current picture for the future of hair loss treatments is perhaps brighter than ever before, Paus believes that there are still some fundamental questions about the science of hair growth that need to be understood. If addressed in the coming years, they could well go a long way to solving baldness for good.
“One of the biggest mysteries about hair follicles is that these tiny mini-organs follow an autonomous inbuilt clock that drives it through this cycle of growth, regression, resting,” he said.
“This clock sits in the follicle itself but we don’t know the mechanism that regulates it. If we understood how this organ actually ticks, we could target it pharmacologically. Drugs that can interfere with this inbuilt clock mechanism in the human hair follicle would be very powerful hair drugs.”
Images via A. Slynko and Shutterstock