In the world of pharmaceuticals, the story of flibanserin, commonly known as “female Viagra” or Addyi, is a fascinating yet controversial one. It serves as a microcosm of the intricate interplay between scientific research, societal values, and corporate interests.
Flibanserin’s origins can be traced back to the 1990s when Boehringer Ingelheim, a German pharmaceutical giant, developed it as an antidepressant. However, clinical trials showed disappointing results in treating depression, and the drug seemed destined for the scrapheap. But then, an unexpected discovery was made. Female patients reported an increase in their sexual desire while taking the medication. With the growing recognition of Hypoactive Sexual Desire Disorder (HSDD) among women and the limited effectiveness of traditional treatments, Boehringer Ingelheim saw a new opportunity and shifted its focus.
The drug’s mechanism of action is unique, with its “dual receptor modulation” property, acting on 5-HT1A and 5-HT2A receptors, and promoting the release of dopamine and norepinephrine, which are associated with sexual arousal and attention. But the road to market approval was anything but smooth.
In 2009, Boehringer Ingelheim submitted flibanserin to the FDA for approval. The FDA, however, rejected the application. The self-report data showed that while the drug increased the average number of sexually satisfying events per month from 2.8 to 4.5, the placebo also had a significant effect, increasing it from 2.7 to 3.7. After accounting for the placebo effect, the drug’s efficacy was only a meager 0.7 additional events per month. Moreover, data from electrode recorders, which the FDA favored, showed no significant difference between flibanserin and the placebo.
Undeterred, Boehringer Ingelheim transferred the rights of flibanserin to Sprout Pharmaceuticals in 2011. Sprout attempted to address the FDA’s concerns by expanding the sample size of the clinical trials and eliminating the electrode recorder data. The new data in 2013 showed a slight increase in sexual satisfaction, but the drug also came with a laundry list of side effects, including low blood pressure, drowsiness, dizziness, and nausea. Once again, the FDA refused to approve the drug.
Faced with these setbacks, Sprout took a different approach. It played the gender equality card. Sprout pointed out that over the past few decades, the FDA had approved 26 drugs for male sexual dysfunction but not a single one for female sexual dysfunction. They established the “Even the Score” organization, launched a massive publicity campaign, and accused the FDA of discrimination against women. This public opinion pressure forced the FDA to clarify that most of the so-called 26 drugs for male sexual dysfunction were different formulations of the same drug, and it had not approved any drugs for male hypoactive sexual desire either.
In 2015, under the intense public scrutiny and after a long hearing and debate, the FDA’s advisory committee voted 18 to 6 in favor of the drug’s approval, deeming its benefits outweighed the risks. In August of the same year, the FDA finally approved flibanserin for the treatment of premenopausal women with HSDD, but with a “black box warning” to highlight its serious side effects.
However, the commercial success that Sprout and the subsequent acquirer, Valeant Pharmaceuticals, hoped for did not materialize. In the first four months after its launch, Addyi’s sales were a paltry $9 million, a far cry from the $320 million that Viagra achieved in the same period.
Moreover, the medical community has been increasingly critical of flibanserin. The Journal of the American Medical Association in 2015 pointed out the imperfect pharmacological data of flibanserin. In 2016, the Annals of Internal Medicine criticized its minimal efficacy and significant toxicity. In 2018, the Journal of Industrial Psychiatry even questioned the very existence of HSDD.
The saga of flibanserin is indeed a rollercoaster ride. It is a story that goes beyond the realm of medicine, touching on issues of scientific ethics, gender equality, and the power of capital. It reminds us that the process of bringing a drug to market is not just about scientific evidence but also about the influence of public opinion and corporate strategies. As we continue to develop new medications, we must strive to balance these various factors to ensure that the drugs we approve are truly safe, effective, and in the best interests of patients.
I wonder if you’ve ever noticed that there is often a sign placed in front of street pharmacies, with six characters written on it: Viagra is in stock.
What on earth is “Viagra”? Why does it occupy the most prominent advertising space in pharmacies?
In fact, “Viagra” is what people usually refer to as “Wei Ge”. This little blue pill, since its debut in 1998, has brought a trillion – dollar – scale frenzy to the male sexual health market. However, while countless male patients have benefited from it, many women deeply troubled by sexual dysfunction also hope that there will be a “female Viagra” to save their lives. Against this backdrop, the little pink pill – Addyi – came into being.
Unfortunately, this drug did not set off a revolution in the field of sexual health like Viagra. On the contrary, since its birth, it has been caught in a fierce debate that has lasted for decades. Its development history further reflects the magical spectrum when scientific rationality, capital ambition, and social movements collide.
I. Planting willows without intention
The generic name of Addyi is flibanserin. It was initially developed as an antidepressant product in the 1990s by Boehringer Ingelheim, a German pharmaceutical giant. Its original design was based on the 5-hydroxytryptamine (5-HT) receptor regulation mechanism, attempting to treat depression by regulating the balance of neurotransmitters in the brain.
However, the subsequent clinical trial results showed that the drug had poor efficacy in treating depression, or could even be said to have no effect at all. This inevitably frustrated the researchers and made Boehringer Ingelheim consider halting further development. At this impasse, the researchers suddenly noticed an interesting phenomenon. In the self-inspection reports submitted, many female depression patients reported that their libido had increased during the period of taking the drug.
At that time, Hypoactive Sexual Desire Disorder (HSDD) was attracting the attention of the medical community. HSDD falls within the category of female sexual dysfunction diseases and is a mental urogenital system disease that can occur in women of all age groups. According to disease epidemiological surveys, the incidence of HSDD in premenopausal women worldwide is approximately 10%. Due to the large number of people affected by HSDD and the extremely limited effectiveness of traditional drug treatments, the accidental discovery of flibanserin delighted the research team and led them to re-evaluate the application direction of this drug. This experience seems to be similar to that of “Viagra”.
Subsequent research indicates that the mechanism of action of flibanserin is not the single pathway of traditional antidepressants, but rather it has a unique “dual receptor regulation” property, namely, an agonistic effect on the 5-HT1A receptor and an antagonistic effect on the 5-HT2A receptor (blocking this receptor can reduce its negative regulation of sexual desire). In addition, it can also indirectly promote the release of dopamine and norepinephrine, two neurotransmitters that help enhance sexual excitement and improve concentration.
After having a new research direction, Boehringer Ingelheim once again invested a large amount of money in the following years to conduct human trials of flibanserin, and this time the subjects of the experiment were women suffering from HSDD.
II. Campaigning for FDA Approval
In 2009, Boehringer Ingelheim confidently submitted a new drug approval application to the FDA with phase III clinical trial data. However, after reviewing the application materials, the FDA decisively rejected the application. The reason was that although the self-inspection report data showed that the drug could increase the average monthly number of sexual satisfactions of patients (from an average of 2.8 times to 4.5 times), the placebo in the experiment could also achieve similar results (from an average of 2.7 times to 3.7 times). As a result, after deducting the placebo effect, the efficacy of flibanserin was only an increase of 0.7 times per month. In addition, from the data results of the electrode recorder, which the FDA was more willing to believe, there was no significant difference between flibanserin and the placebo.
After this setback, Boehringer Ingelheim was completely disheartened. So in 2011, it transferred flibanserin to another company, Sprout Pharmaceuticals, thus rewriting the fate of flibanserin.
Upon taking over flibanserin, Sprout immediately evaluated the FDA’s approval opinions. Perhaps there were intense internal discussions, or perhaps they consulted some “experts”. In any case, they finally made a bizarre decision: First, expand the human sample size and conduct the experiment again, attempting to justify themselves with more self – inspection report data. Second, cancel the data recording of the electrode recorder to silence the FDA. Such actions are no different from taking advantage of loopholes.
In 2013, new clinical trial data were released. As Sprout had anticipated, the self-inspection report showed that after taking flibanserin for 24 weeks, patients had an average monthly increase of 0.5 sexually satisfying experiences, which was consistent with previous experimental results. On the other hand, its side effects were truly astonishing. Symptoms such as low blood pressure, drowsiness, dizziness, and nausea occurred frequently. However, Sprout didn’t take this seriously and still insisted on submitting an application to the FDA. But the FDA was not to be trifled with. Sprout’s clever pharmacodynamic evaluation indicators failed to convince the experts in the field. In addition, the severe toxic and side effects couldn’t be ignored. Ultimately, the new drug application for flibanserin was rejected by the FDA again.
III. Reversal of the Situation
Failing twice in a row at the FDA shows that this drug really doesn’t work well. If it were other manufacturers, it would probably have been abandoned long ago. But Sprout is extremely stubborn and can’t bear to see its efforts go to waste. Perhaps there were intense discussions within the company, or perhaps some “experts” were consulted again. In any case, a decision was finally made to ensure its invincibility: playing the card of gender equality.
Sprout’s statistics show that in the past few decades, the FDA has approved 26 drugs for male sexual dysfunction, but not even one for female sexual dysfunction. Is this reasonable? Is this fair? Isn’t this blatant discrimination against women? Regardless of the facts, this statement is an unrefusable political correctness. With this breakthrough point, Sprout immediately launched a large – scale publicity campaign.
In 2013, Sprout funded and established a gender equality movement organization named “Even the Score”. This organization not only made a big splash in online media about the FDA’s discrimination against women in new drug reviews, but also wrote letters to the then members of Congress, asking them to investigate such despicable behavior of the FDA. This instant public opinion bomb caught the FDA off guard, forcing the FDA to come forward and clarify that most of the so – called 26 drugs for male sexual dysfunction on the market were actually multiple dosage forms of one drug. Moreover, the FDA had never approved any drug for treating male hypoactive sexual desire, so there was no discrimination.
By taking advantage of this wave of public opinion, Sprout once again submitted a new drug application for flibanserin to the FDA in a timely manner. In June 2015, after a long hearing and debate, the FDA Advisory Committee finally concluded, with 18 votes in favor and 6 votes against, that the efficacy of the drug outweighed the risks. In August of the same year, the FDA officially approved the marketing of flibanserin (Addyi) for the treatment of hypoactive sexual desire disorder in premenopausal women, but required that the drug must be labeled with a “black box warning”, which is used to indicate the most serious adverse reactions of the drug.
The day after flibanserin was approved, Even the Score symbolically posted a video on social media to celebrate and took the opportunity to thank the FDA. Perhaps because it had accomplished its mission, the account disappeared from the internet after updating its last tweet in January 2016. Similarly, its official website also showed that it was impossible to log in.
IV. The Tide Ebbs and the Sand Levels
Perhaps inferring the infinite prospects of flibanserin from “Viagra”, Valeant Pharmaceuticals announced the acquisition of Sprout for one billion US dollars just two days after its approval. However, the harsh reality sent chills down Valeant’s spine. Data shows that the sales volume of Addyi in the first four months after its launch was only 9 million US dollars, while during the same period, the sales volume of “Viagra” reached an astonishing 320 million US dollars. It seems that Valeant’s dream of replicating the sales miracle of “Viagra” is nothing but a pipe dream after all.
Not only that, the criticism of flibanserin in the medical community has also intensified. In 2015, the Journal of the American Medical Association published an article pointing out that the pharmacological data of flibanserin was extremely incomplete and full of loopholes; in 2016, the Journal of Internal Medicine also criticized the negligible efficacy and significant toxicity of flibanserin; in 2018, the Journal of Industrial Psychiatry even questioned the existence of HSDD…
If there is no “disease”, where can the “medicine” attach? Although the bumpy origin of flibanserin seems like a farce, it also reveals the complex ecosystem of drugs moving from the laboratory to the market. This inevitably triggers people’s profound reflection on scientific ethics, gender equality, and capital power.
6. Current Limitations and Future Directions
