There hasn’t been a lot of hair loss treatment progress in the last twenty years. However several biotech companies are hot on the case and are getting tantalizingly close to the breakthrough that many patients hope for. 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 depression.
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Bridging the gap in preventative treatments
Preventative treatments are scarce. Until recently, the only drugs approved by regulators were Minoxidil and Propecia, both of which are only marginally effective at halting hair loss, and the former is the only treatment available to women.
Over the past decade, cosmetic surgery has looked to ease the burden. The market value of the global hair transplant industry is therefore predicted to exceed €24 billion ($28 billion) by 2027. 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 biotechs view this as an opportunity.
“The number of patients waiting for new treatment options is huge,” said Jan Alenfall, chief scientific officer at Follicum, a Swedish biotech working on treatments for hair loss and diabetes.
“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.”
Jan Alenfall, CSO at Follicium
Revisiting topical therapies
It was a research breakthrough that inspired Follicum’s development of its hair loss treatment. 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 visible hairs again.
However, Follicum’s story reflects the difficulties faced by researchers developing hair loss treatments. In June 2021, the company was forced to discontinue the development of its lead candidate for hair loss after the results of a phase 2a trial showed no significant difference from the placebo group. Follicum is now exploring other avenues for its drug candidate, but this was yet another hit to a condition that requires more attention from drug developers.
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, chief executive officer (CEO) of Cassiopea. “And those follicles that aren’t completely shut down due to DHT, they start producing hair again.”
Helping women with hair loss
A key reason why biotechs are so keen to develop topical treatments for hair loss 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 hormone levels. 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. Avoiding hormonal pathways altogether is therefore seen as a promising approach.
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 embarked on a phase 2 trial of its lead product in female patients and published the first positive results in September 2021. However, to this day, we still have too little data available on Breezula’s efficacy and safety.
“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.”
As some solutions carry hope, patients suffering from hair loss will need to keep waiting to see the treatment they have been looking for.
Triggering hair growth and addressing alopecia areata with JAK inhibitors
Alopecia areata is an autoimmune condition characterized by the sudden and often unpredictable loss of hair on the scalp and sometimes on other parts of the body. This condition occurs when the immune system mistakenly attacks hair follicles, leading to hair loss, typically in small round patches that can become more extensive in some cases.
The exact cause of alopecia areata is not fully understood, but it is believed to involve a combination of genetic and environmental factors. The condition can affect individuals of all ages, genders, and ethnic backgrounds, but it often first appears in childhood or early adulthood. While the hair loss associated with alopecia areata can be distressing, it’s important to note that the condition does not cause physical illness.
Eily Lilly and Pfizer have been neck and neck in a race to gain approval for two drugs that had shown promise in phase 3 trials against alopecia.
Developed and marketed by Eli Lilly, Olumiant functions as a Janus kinase (JAK) inhibitor, targeting the pathways involved in the immune attack on hair follicles. By inhibiting these pathways, Olumiant reduces inflammation and promotes hair regrowth.
Approved by the U.S. Food and Drug Administration (FDA) in June 2022 for adults with severe alopecia areata, Olumiant was the first systemic medication to be authorized for this condition. Clinical trials have demonstrated its efficacy, showing that a significant percentage of participants achieved considerable scalp hair regrowth after 36 weeks of treatment.
While Olumiant offers hope for those suffering from severe alopecia areata, it comes with a range of potential side effects and risks, including serious infections, increased risk of death in older individuals with heart disease risk factors, and the possibility of major cardiovascular events.
A year after Olumniant’s approval, in June 2023, the FDA approved the second JAK inhibitor treatment for alopecia areata, Litfulo. This solution developed by Pfizer is the first treatment approved for adolescents alongside adults with alopecia areata, highlighting its importance in addressing the needs of a younger demographic often deeply impacted by the psychological and social aspects of hair loss.
In clinical trials, notably the ALLEGRO phase 2b/3 trial, Litfulo demonstrated significant efficacy in promoting hair regrowth, with 23% of participants achieving substantial scalp hair coverage after six months of treatment. However, like Olumniant, Litfulo comes with potential side effects and risks. These include serious infections, higher rates of malignancies including non-melanoma skin cancer and lymphoma, cardiovascular events, and blood clots.
These drugs are known to block the activity of cytokines – small inflammatory proteins – and therefore lower immune responses. JAK inhibitors can be used for the treatment of cancer and autoimmune diseases, such as rheumatoid arthritis. These JAK inhibitors have true potential in treating alopecia areata but still represent important risk factors for patients. Research and development still have a long way to go to address this condition in a safer way.
Research still needs to mature in hair loss treatment
While these companies are studying different avenues for existing and novel compounds, others aim to try and understand more about the molecular mechanisms that underpin human hair growth and loss. The goal is to find an entirely new class of hair drugs and many companies are investing in early-stage research.
Italian biotech Giuliani, for example, has been exploring one particularly innovative way of reviving dormant hair follicles in hair loss patients. By studying existing drugs for other conditions that cause unwanted body hair growth as a side effect over the past four years, it has identified completely new pathways for stimulating hair follicles.
While the current picture for the future of hair loss treatments is perhaps brighter than ever before, Ralf Paus, a consultant scientist for Giuliani 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 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.”
Ralf Paus consultant scientist at Giuliani
In other words, a deeper understanding of the mechanism behind hair loss is essential for the industry to progress faster in the area and develop more effective treatments.
New technologies related to hair loss treatment:
This article was originally published in February 2021 by David Cox and has since been updated by Jules Adam on February 2024.