There has not been much progress in the treatment of hair loss in the last twenty years. However, several biotech companies are taking up the cause and are coming tantalizingly close to the discovery that many patients hope for. With body dysmorphia magnified by the ubiquitous digital world, psychiatrists are increasingly linking the appearance of male and female pattern baldness to mental health conditions ranging from anxiety to depression.
Bridging the gap in preventive treatments
Preventive treatments are rare. Until recently, the only drugs approved by regulators were Minoxidil and Propecia, both of which are only marginally effective in stopping hair loss, and the former is the only treatment available for women.
Over the past decade, cosmetic surgery has seemed to lighten the burden. The market value of the global hair transplant industry is thus was foreseen to exceed €24 billion ($28 billion) by 2027. However, hair transplants are not a panacea, as they can be expensive and sometimes painful. Consequently, there is a huge market for any new product that can effectively stop baldness in its tracks, and a number of artisans see 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, therefore, it is also associated with infections. In addition, many patients tend to need more than one transplant since the hair loss process generally continues.”
Topical Remedies Review
It was a research discovery that inspired the development of Follicum hair loss treatment. While studying treatments for arteriosclerosis – a thickening and hardening of the artery walls that often occurs in old age – scientists at Lund University in Sweden discovered that a variant of the protein osteopontin – a natural molecule in our bodies – could grow hair development in mice.
Subsequent studies found that this protein variant has a very specific target in 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 hair again.
However, Follicum’s story reflects the difficulties faced by researchers developing hair loss treatments. In June 2021, the company was forced to growth arrest of the 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 the drug candidate, but this was yet another blow to a condition that requires more attention from drugmakers.
The reason baldness occurs is that the hair follicles become sensitive to scalp hormones, mainly dihydrotestosterone (DHT), which binds to the 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 the study of the role of the hormone in the development of acne.
“Our drug actually counteracts the negative effect of DHT around the follicle, slowing or stopping hair loss.,explained Diana Harbort, CEO of Cassiopea. “And those follicles that haven’t completely closed due to DHT, start producing hair again.”
Helping women with hair loss
A key reason biotechs are so eager 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. Furthermore, because it acts systemically, it is not safe to use in women suffering from hair loss, a patient group that has traditionally been neglected by the field. Therefore, complete avoidance of hormonal pathways is considered a promising approach.
While Cassiopea’s product works on DHT, the topical nature of the treatment means it doesn’t come with the safety warnings of oral medications, and studies so far show few side effects. As a result, the company began a phase 2 trial of its lead product in female patients and published the first positive results in September 2021. However, to date, we still have very little data available on the effectiveness and safety of Breezula.
“There are so few treatment options that really work for hair loss, and it’s really problematic because of the cycle of social complications that really affect a patient’s self-esteem,” Harport said. “It’s very embarrassing for them, and studies show that women are even more likely to suffer from these psychological complications than men, so there is a huge unmet need.”
As some solutions bring hope, patients suffering from hair loss will have to continue to wait to see the treatment they have been looking for.
Activation of hair growth and treatment of 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, usually 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 people of any age, gender and ethnicity, but often first appears in childhood or early adulthood. While the hair loss associated with alopecia areata can be painful, it is important to note that the condition does not cause a physical illness.
Eily Lilly and Pfizer have been in a race to win approval for two drugs that have shown promise in phase 3 trials against alopecia.
Developed and marketed by Eli Lilly, Olumiant works as a Janus kinase (JAK) inhibitor, targeting pathways involved in immune attack on hair follicles. By inhibiting these pathways, Olumiant reduces inflammation and promotes hair regeneration.
Approved by the US Food and Drug Administration (FDA) in June 2022 for adults with severe alopecia areata, Olumiant was the first systemic drug approved for this condition. Clinical trials have proven its effectiveness, showing that a significant percentage of participants achieved significant scalp hair regrowth after 36 weeks of treatment.
While Olumiant offers hope to those with severe alopecia areata, it comes with a number of potential side effects and risks, including serious infections, an increased risk of death in older people with heart disease risk factors, and the possibility of serious cardiovascular events.
One year after Olumniant was approved, in June 2023, the FDA was approved the second JAK inhibitor treatment for alopecia areata, Litfulo; This Pfizer-developed solution is the first treatment approved for adolescents along with adults with alopecia areata, highlighting its importance in addressing the needs of a younger population that is often deeply affected by the psychological and social aspects of hair loss.
In clinical trials, especially the ALLEGRO 2b/3 test phaseLitfulo demonstrated significant effectiveness in promoting hair regeneration, with 23% of participants achieving substantial scalp hair coverage after six months of treatment. However, like Olumniant, Litfulo has 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 reduce immune responses. JAK inhibitors can be used to treat cancer and autoimmune diseases such as rheumatoid arthritis. These JAK inhibitors have real potential in the treatment of alopecia areata, but still represent significant risk factors for patients. Research and development still has a long way to go to deal with this situation in a safer way.
Research has yet to mature in the treatment of hair loss
While these companies are studying different avenues for existing and new compounds, others aim to try to understand more about the molecular mechanisms that underpin human hair growth and loss. The goal is to find a whole new class of hair drugs, and many companies are investing in early-stage research.
The Italian biotech Giuliani, for example, has explored a particularly innovative way of reviving dormant hair follicles in patients with hair loss. By studying existing drugs for other conditions that cause unwanted body hair growth as a side effect over the past four years, he has identified entirely new pathways for stimulating hair follicles.
While the current picture for the future of hair loss treatments is perhaps brighter than ever, Ralf Paus, Giuliani’s scientific advisor believes there are still some fundamental questions about the science of hair growth that need to be understood. If treated in the coming years, they could go a long way in solving baldness for good.
“One of the biggest mysteries about hair follicles is that these tiny mini-organs follow an autonomous built-in clock that drives them through this growth, regression, rest cycle,” 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 really ticks, we could target it pharmacologically. Drugs that can affect this built-in clock mechanism in the human hair follicle would be very powerful hair drugs.”
In other words, a deeper understanding of the mechanism behind hair loss is essential for faster industry progress in the area and the development of more effective treatments.
New technologies related to the treatment of hair loss:
This article was originally published in February 2021 by David Cox and has since been updated by Jules Adam in February 2024.
