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Deleted member 7076
Kraken
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INTRO
RU58841 was one of the most promising compounds for the treatment of androgenic alopecia. However, there are a lot of questions regarding the studies and why the research was discontinued.
ROUSSEL UCLAF
RU58841 was first researched by French pharmaceutical company Roussel Uclaf. Multiple studies on animals were conducted. It produced good results on hamster prostate without systemic absorption (1). It was said that RU58841 is a potent androgen receptor inhibitor capable of blocking 70% of DHT binding (2). Topical RU58841 5% was applied to the bald scalp of stumptailed macaques. There was an increased number of anagen follicles and a decreased number of telogen follicles. Systemic effects were not recorded (3). In another study, RU58841 dosed at 100-fold the therapeutic tested range, showed no signs of systemic antiandrogenic effects (4). Topically applied RU58841 had no systemic effects on hamsters (5).
RU58841 DISCONTINUATION
Roussel Uclaf was bought by german company Hoechst AG in 1997. This resulted in a lot of changes. The following text was from a french forum (6):
This purely financial logic has consequences in all areas: human, scientific, economic and social. Jean-Pierre Godard, chairman of the Roussel-UCLAF management board and of the HMR executive committee, indicated in June 1996: “More than 50% of job cuts in France and Germany have been carried out to date, while restructurings will ultimately affect 10% of the group's employees. " Many research projects have been abandoned: out of 65 projects in development that existed before 1995, the HMR group has decided to keep only about forty, considering that only “three therapeutic axes are essential” for the pharmaceutical industry (the central nervous system, anti-infectives and the cardiovascular system). For its part, Roussel-UCLAF is forced to reduce its activity sectors. The fields of immunology and endocrinology are closed.
This can be verified by a french newspaper article stating (7):
The new distribution of fields has in fact forced it to reduce its areas of work from four to two, abandoning endocrinology and immunology-rheumatology in the process. All in all, the rationalization implemented by HMR, the effects of which should be visible from the end of 1997 in terms of operational profitability, sales growth and a 30% reduction in research lead times, affects around 10% of the total Roussel-Uclaf workforce (8,000 people).
Roussel Uclaf was also in trouble because of RU-486, the first ever abortion pill, that caused a lot of outrage and demonstrations. This may have influenced the company aswell (8). According to the data, the research of RU58841 was stopped because of financial issues and not because of the substance itself.
PROSTRAKAN
RU58841 was then picked up by Prostrakan and it’s french drug discovery subsidiary Proskelia. It was renamed PSK3841. Proskelia performed Phase 1 and Phase 2a trials on humans in france. Phase 1 Trials were done under the supervision of Dr. Evelyne Guénolé: A double blind, randomised, vehicle-controlled, safety and tolerance study of topical PSK 3841 solution at 5% administered twice daily over four weeks to healthy Caucasian males with androgenetic alopecia. Phase 2 Trials were done under the supervision of Dr Dominique Van Heste: A multi-centre, double-blind, randomised, vehicle-controlled study for a quantitative estimation of hair re-growth in male subjects with androgenetic alopecia treated over 6 month with two ethanolic PSK 3841 solutions (2.5% and 5%)
Since Proskelia and Prostrakan have been bought by Kyowa Kurin, the Proskelia Website does not exist anymore. However, it can be accessed through the google wayback machine. Source: http://web.archive.org/web/20040606184418/http://www.proskelia.com/rd_32.htm
The complete trial results were never published. However Proskelia released the following statement:
"Topical Anti-Androgen PSK 3841 is an innovative molecule with a unique mechanism of action for the treatment of androgen-dependent conditions, such as alopecia and acne. In pre-clinical studies, it has shown promising activity in various animal models of acne, alopecia and hirsutism. The product has good systemic and dermal tolerance. In human clinical pharmacology, there was no systemic anti-androgenic activity and again good general and dermal tolerance. PSK 3841 has completed several Phase I studies and is currently in Phase II for alopecia. A clinical proof of principle phase II study in acne is also ongoing. This product is available for licensing."
This statement existed for multiple years on the Prostrakan Website. It says, that there were no systemic anti-androgenic effects during Phase 1 and 2a trials on humans and it was well tolerated. If PSK3481 had severe side effects in clinical trials, this statement would have not been published and would not have remained on the official website until 2009/2010 (4 years after the trials ended). In 2011 Prostrakan was bought by japanese company Kyowa Kirin, which resulted in a new website. This is the time when all information about PSK3841 dissapeared from the website. It is very likely, that Kyowa Kirin was not interested in continuation of the research.
So why wasn’t the research continued? In the development plan from Prostrakan it reads "Following the Strakan/Proskelia merger, management identified three mid-stage projects that it believes contain value but are not priority. The company has said that it is in active discussion with a number of potential partners" The plan specifically lists PSK3841 (Ru58841) as a non-priority. It said: "We believe the market for this agent is reasonably modest- US$100-200 million-but that it could be of interest to a speciality dermatology company." I think the most likely explanation is that there was simply no company, who would invest in the research, And since Ru58841 was a non-priority, it was stopped. There are three treatments listed as non-priorities, that require out-licensing:
- nitric oxide for onychomycosis (9)
- PSk3841 against alopecia (10)
- PSK3987-Trimegestone Patch for HRT and contraception (11)
All of these 3 researches were stopped. So either all of these treatments had sudden side effects, or there simply wasn't enough money. Notice how the Statement on Prostrakan and Proskelia Website says: This product is available for licensing. They were searching for a company, that would like to continue the trials, but they apperently they did not found any.
TLDR
RU58841 was one of the most promising compounds for the treatment of androgenic alopecia. However, there are a lot of questions regarding the studies and why the research was discontinued.
ROUSSEL UCLAF
RU58841 was first researched by French pharmaceutical company Roussel Uclaf. Multiple studies on animals were conducted. It produced good results on hamster prostate without systemic absorption (1). It was said that RU58841 is a potent androgen receptor inhibitor capable of blocking 70% of DHT binding (2). Topical RU58841 5% was applied to the bald scalp of stumptailed macaques. There was an increased number of anagen follicles and a decreased number of telogen follicles. Systemic effects were not recorded (3). In another study, RU58841 dosed at 100-fold the therapeutic tested range, showed no signs of systemic antiandrogenic effects (4). Topically applied RU58841 had no systemic effects on hamsters (5).
RU58841 DISCONTINUATION
Roussel Uclaf was bought by german company Hoechst AG in 1997. This resulted in a lot of changes. The following text was from a french forum (6):
This purely financial logic has consequences in all areas: human, scientific, economic and social. Jean-Pierre Godard, chairman of the Roussel-UCLAF management board and of the HMR executive committee, indicated in June 1996: “More than 50% of job cuts in France and Germany have been carried out to date, while restructurings will ultimately affect 10% of the group's employees. " Many research projects have been abandoned: out of 65 projects in development that existed before 1995, the HMR group has decided to keep only about forty, considering that only “three therapeutic axes are essential” for the pharmaceutical industry (the central nervous system, anti-infectives and the cardiovascular system). For its part, Roussel-UCLAF is forced to reduce its activity sectors. The fields of immunology and endocrinology are closed.
Cette logique uniquement financière a des conséquences dans tous les domaines: humains, scientifiques, économiques et sociaux. Jean-Pierre Godard, le président du directoire de Roussel-UCLAF et du comité exécutif de HMR, indiquait en juin 1996: «Plus de 50% des suppressions d'emplois en France et en Allemagne ont été réalisées à ce jour, alors que les restructurations affecteront au final 10% des salariés du groupe.» De nombreux projets de recherches sont abandonnés: sur 65 projets en développement qui existaient avant 1995, le groupe HMR a décidé de n'en garder qu'une quarantaine, estimant que seuls «trois axes thérapeutiques sont incontournables» pour l'industrie pharmaceutique (le système nerveux central, les anti-infectieux et le système cardio-vasculaire). Pour sa part, Roussel-UCLAF se voit imposer une réduction de ses secteurs d'activité. Les domaines de l'immunologie et de l'endocrinologie sont arrêtés.
This can be verified by a french newspaper article stating (7):
The new distribution of fields has in fact forced it to reduce its areas of work from four to two, abandoning endocrinology and immunology-rheumatology in the process. All in all, the rationalization implemented by HMR, the effects of which should be visible from the end of 1997 in terms of operational profitability, sales growth and a 30% reduction in research lead times, affects around 10% of the total Roussel-Uclaf workforce (8,000 people).
La nouvelle répartition des domaines l'a en ef- fet obligé à ramener de quatre
à deux ses axes de travail, abandonnant au passage l'endocrino- logie et l'immunologie- rhumatologie. Au total, la rationali- sation mise en oeuvre par HMR, dont les ef- fets devront être visibles dès la fin 1997 en termes de rentabilité opé- rationnelle, de croissance des ven- tes et de réduction de 30 % des délais en recherche, touche envi- ron 10 % des effectifs totaux de Roussel-Uclaf ( 8000 personnes ).
à deux ses axes de travail, abandonnant au passage l'endocrino- logie et l'immunologie- rhumatologie. Au total, la rationali- sation mise en oeuvre par HMR, dont les ef- fets devront être visibles dès la fin 1997 en termes de rentabilité opé- rationnelle, de croissance des ven- tes et de réduction de 30 % des délais en recherche, touche envi- ron 10 % des effectifs totaux de Roussel-Uclaf ( 8000 personnes ).
Roussel Uclaf was also in trouble because of RU-486, the first ever abortion pill, that caused a lot of outrage and demonstrations. This may have influenced the company aswell (8). According to the data, the research of RU58841 was stopped because of financial issues and not because of the substance itself.
PROSTRAKAN
RU58841 was then picked up by Prostrakan and it’s french drug discovery subsidiary Proskelia. It was renamed PSK3841. Proskelia performed Phase 1 and Phase 2a trials on humans in france. Phase 1 Trials were done under the supervision of Dr. Evelyne Guénolé: A double blind, randomised, vehicle-controlled, safety and tolerance study of topical PSK 3841 solution at 5% administered twice daily over four weeks to healthy Caucasian males with androgenetic alopecia. Phase 2 Trials were done under the supervision of Dr Dominique Van Heste: A multi-centre, double-blind, randomised, vehicle-controlled study for a quantitative estimation of hair re-growth in male subjects with androgenetic alopecia treated over 6 month with two ethanolic PSK 3841 solutions (2.5% and 5%)
Since Proskelia and Prostrakan have been bought by Kyowa Kurin, the Proskelia Website does not exist anymore. However, it can be accessed through the google wayback machine. Source: http://web.archive.org/web/20040606184418/http://www.proskelia.com/rd_32.htm
The complete trial results were never published. However Proskelia released the following statement:
"Topical Anti-Androgen PSK 3841 is an innovative molecule with a unique mechanism of action for the treatment of androgen-dependent conditions, such as alopecia and acne. In pre-clinical studies, it has shown promising activity in various animal models of acne, alopecia and hirsutism. The product has good systemic and dermal tolerance. In human clinical pharmacology, there was no systemic anti-androgenic activity and again good general and dermal tolerance. PSK 3841 has completed several Phase I studies and is currently in Phase II for alopecia. A clinical proof of principle phase II study in acne is also ongoing. This product is available for licensing."
This statement existed for multiple years on the Prostrakan Website. It says, that there were no systemic anti-androgenic effects during Phase 1 and 2a trials on humans and it was well tolerated. If PSK3481 had severe side effects in clinical trials, this statement would have not been published and would not have remained on the official website until 2009/2010 (4 years after the trials ended). In 2011 Prostrakan was bought by japanese company Kyowa Kirin, which resulted in a new website. This is the time when all information about PSK3841 dissapeared from the website. It is very likely, that Kyowa Kirin was not interested in continuation of the research.
So why wasn’t the research continued? In the development plan from Prostrakan it reads "Following the Strakan/Proskelia merger, management identified three mid-stage projects that it believes contain value but are not priority. The company has said that it is in active discussion with a number of potential partners" The plan specifically lists PSK3841 (Ru58841) as a non-priority. It said: "We believe the market for this agent is reasonably modest- US$100-200 million-but that it could be of interest to a speciality dermatology company." I think the most likely explanation is that there was simply no company, who would invest in the research, And since Ru58841 was a non-priority, it was stopped. There are three treatments listed as non-priorities, that require out-licensing:
- nitric oxide for onychomycosis (9)
- PSk3841 against alopecia (10)
- PSK3987-Trimegestone Patch for HRT and contraception (11)
All of these 3 researches were stopped. So either all of these treatments had sudden side effects, or there simply wasn't enough money. Notice how the Statement on Prostrakan and Proskelia Website says: This product is available for licensing. They were searching for a company, that would like to continue the trials, but they apperently they did not found any.
TLDR
- Roussal Uclaf stopped research of RU58841 because the endocrinological department was closed after being bought by Hoechst AG.
- According to the official ProStrakan Website PSK3481 was well tolerated in humans and did not show systemic androgenic effects in the 6 month trial.
- Research of PSK3841 was most likely stopped because they were not able to outsource the product to another company. When ProStrakan was bought by Kyowa Kurin, the project got cancelled.
- There are no indications of severe side effects, although there is no data on long-term effects.
