S1 Biopharma's approach to the treatment of hypoactive sexual desire disorder (HSDD), and an overview of what's coming down the pipeline.
Approximately one in 10 women suffer from HSDD—defined as a woman's chronic or ongoing lack of interest in sex—according to Even the Score, a women's sexual health campaign supported by Sprout Pharmaceuticals.
However, HSDD is a condition that both men and women face, though a greater number of women tend to have HSDD.
S1 Biopharma, Inc., a clinical-stage biopharmaceutical company focused on the treatment of sexual dysfunction in both women and men, and CKD Pharmaceuticals are investigating Lorexys™, S1 Biopharma’s investigational therapy currently positioned to advance to a Phase 2b clinical trial for treatment of HSDD in women.
Nick Sitchon, CEO of S1 Biopharma, participated in a Q&A about HSDD and what's coming down the pipeline.
Q: What are some of the stigmas that surround HSDD?
Sitchon: Although HSDD affects over 12 million women and 8 million men in the U.S. alone, it is widely misunderstood.
It is characterized by “low sexual desire that causes marked distress or interpersonal difficulty and is not due to a co-existing medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance."1
It is especially important to note that HSDD is a psychiatric disorder rather than a physical disorder, as can be the case with other sexual dysfunctions, such as erectile dysfunction (ED) or pain during intercourse. It is the most common female sexual dysfunction (FSD), affecting about one in ten women. It is often misdiagnosed and undertreated, due in part to cultural biases against treated diminished sexual desire, especially in women. Patients are often too embarrassed to discuss their sex lives with their doctors. In many cases, practitioners may also be unsure how to address the topic with their patients.
Q: In the past, what has been the go-to treatment for HSDD in women? In men?
Sitchon: Until the approval of Addyi (flibanserin) for HSDD in premenopausal women, there were no approved treatments for HSDD in women or men. Women who discussed symptoms of HSDD with their doctors prior to the approval of Addyi might have been advised to seek talk therapy or couples counseling, or may have tried off-label medication, such as bupropion or testosterone.
For men there are several well-known treatments for other sexual dysfunctions, such as Viagra or Cialis, which are approved for the treatment of ED. These treatments might help with the physical component of HSDD. However, it is possible that a number of men who are diagnosed with ED may actually suffer from HSDD as well.
Q: In the past, what has the approach been to researching and creating a treatment for HSDD in women?
Sitchon: Researchers have examined several different approaches to HSDD treatment over time. The “first generation” of treatments was based on hormone therapies, and ultimately were not approved.
The next generation of HSDD treatments, such as Lorexys and Addyi, work on the brain rather than the body, as a healthy libido requires not only hormones, but also a balance of dopamine, norepinephrine, and serotonin.
Addyi is a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist. Lorexys is a combination of bupropion and trazodone, which works to balance neurotransmitters in the brain to restore interest in sex.
Q: How would you describe the current overarching market of HSDD treatment?
Sitchon: The market for HSDD is significant, affecting more than 12 million women and 8 million men in the U.S. alone.
Q: Why, do you think, the sales of the drug Addyi (flibanserin) have been less than optimal?
Sitchon: Addyi sales may have been less than optimal due to:
- Poor efficacy
- In clinical trials, 100 mg of flibanserin was shown to increase the number of satisfying sexual events only by 0.5 to one additional event per month over placebo.
- Dosing and contraindications
- Flibanserin must be taken daily, and it is contraindicated for use with alcohol, which may contribute to lack of patient compliance or an increased number of reported side effects.
- Side effects
- The FDA approved Addyi with a boxed warning to highlight the risks of severe hypotension and syncope in patients who drink alcohol during treatment with Addyi, in those who also use moderate or strong CYP3A4 inhibitors, and in those who have liver impairment.1
- Regulatory restrictions
- The FDA has required both physicians and pharmacists to be certified prior to prescribing or fulfilling Addyi prescriptions. Additionally, there is an 18-month restriction on direct-to-consumer advertising. However, Addyi sales will likely increase with time, as more physicians and pharmacists become certified.
Q: How does Lorexys (a combination of two already FDA-approved drugs, bupropion and trazodone) work?
Sitchon: Lorexys is an oral, non-hormonal, fixed-dose combination of two antidepressants: bupropion and trazodone. It is formulated with a ratio that is precisely balanced to neutralize the side effects of its individual components and maximize efficacy. When taken together, bupropion and trazodone work synergistically to modulate the neurotransmitters NE, DA, and 5HT2 in selective brain areas, ultimately increasing sexual desire. The combination also balances out the effects of each drug to reduce the risk of adverse events.
Q: What led you to the research and development of Lorexys?
Sitchon: I recognized the best way to address this major unmet need was an approach that met both high efficacy and safety/tolerability thresholds. After pilot testing several combinations of potential combinations, Lorexys showed surprisingly strong performance in both areas. Our CMO, Dr. Robert Pyke, was the creator of using Addyi for sexual dysfunction, and an expert with more than 30 years of experience in this area. Dr. Pyke confirmed the basis for success in Lorexys, which was proven again in subsequent studies.
Q: How does the combination of bupropion and trazodone compare to the use of either drug alone in the treatment of HSDD?
Sitchon: Lorexys completed a Phase 2a clinical study that evaluated its safety, tolerability, and pro-sexual efficacy compared to bupropion, one of its constituent drugs. Clinical trial results found Lorexys to be highly tolerable, with minimal side effects, and showed a 38 percent stronger efficacy than the use of bupropion alone. Trazodone by itself is not expected to have success in treating HSDD.
Q: What were some of the findings of the Phase 2a clinical trials of Lorexys?
Sitchon: Phase 2a clinical trials found that Lorexys moderate-dose met goal of >30 percent superiority in responders over control (bupropion).
- On the primary endpoint, FSFI desire, 38 percent more responders seen in Lorexys (76 percent vs. 38 percent)
- The secondary endpoints support the primary endpoint
- 43 percent more responders on FSDS-R item 13 sexual distress (88 percent vs. 45 percent)
- 34 percent more responders on PGIC (58 percent vs. 24 percent)
Q: How does Lorexys target HSDD differently compared to Addyi?
Sitchon: Our proprietary combination of a stimulant and a sedative work to neutralize the effects of each drug while stimulating neurotransmitters in the brain, causing an increase in sexual desire.
Addyi is a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist. In contrast, Lorexys is designed to restore the balance of three neurotransmitters that are known to regulate sexual inhibition and sexual excitation—dopamine, serotonin, and norepinephrine.
Q: Are there other treatments currently in development for HSDD (in addition to Lorexys and Addyi)?
Sitchon: Yes, at S1 we are also developing Orexa for the treatment of HSDD in men. Orexa is just about to begin Phase 2a clinical trial as Lorexys enters into Phase 2b. There is also a large unmet need for HSDD treatments in men, as it affects an estimated 8 million men in the U.S.
Another injectable drug, bremelanotide, which is manufactured by Palatin Technologies, is currently in Phase 3 clinical trials.
Q: What are some of the trends you see developing for the treatment of HSDD in women?
Sitchon: The increased dialogue about HSDD is certainly a part of a larger trend that will hopefully result in reducing some of the stigmas associated with the condition and encourage more women to seek treatment. Common understanding of HSDD is moving from skepticism to understanding of its major impact on quality of life, self image, and marital success.
Q: Do you foresee any of the treatments for HSDD in women impacting the treatment for men?
Sitchon: Our hope is that with more treatments available to treat HSDD in women, more men will be encouraged to speak with their doctors if they feel they might be suffering from HSDD as well. Despite the fact that HSDD affects women and men alike, the focus on men’s sexual dysfunctions has typically centered on ED and low testosterone subtypes. According to the National Health and Social Life Survey of over 1,200 men in 1999, the incidence of male HSDD is approximately 15 percent. This survey also found in men under the age of 30, the incidence of a desire condition was determined to be double that of ED.2 It is entirely possible that some men who are being treated for ED may also be suffering from HSDD.
Q: As a company, what are some of your goals for the upcoming year?
Sitchon: Our focus for 2016 is on execution of clinical trials for both Lorexys and Orexa.
Responses provided by:
Nicolas G. Sitchon, Chief Executive Officer of S1 Biopharma
Nicolas G. Sitchon, M.A., M.B.A. has served as Chairman of our board of directors and as our President and Chief Executive Officer since our founding in October 2010. From October 2008 to October 2010, Mr. Sitchon performed services in anticipation of incorporation of our company and related to the development of our lead product candidate, LorexysTM. From April 2006 to October 2008, Mr. Sitchon was Global Research & Development Controller at Bayer HealthCare Consumer Care, a division of Bayer AG. Prior to that time, Mr. Sitchon held positions in marketing, information technology, business intelligence and business planning in the cardiovascular and neuroscience franchises of the Pharmaceuticals division of Novartis Corporation. Mr. Sitchon received his M.A. in Medical Science from the Boston University School of Medicine and his M.B.A. from the Boston University School of Management. He completed his undergraduate studies at the University of California, Berkeley. Mr. Sitchon was selected to serve as a member of our Board of Directors because of his role in developing, and his extensive knowledge regarding, our product candidates; his experience as our executive officer; because of his proven ability to pursue the development of product candidates in an efficient manner using minimal capital; and because of his advanced degrees in science and business.
About S1 Biopharma, Inc.
S1 Biopharma, Inc. is a clinical-stage biopharmaceutical company focused on the treatment of sexual dysfunction in both women and men. The company's development programs include first-in-class non-hormonal therapies designed to treat diminished sexual desire by restoring the natural balance of key neurotransmitters in the brain. The company's lead product candidate, Lorexys, is currently positioned to advance to a Phase 2b clinical trial for the treatment of hypoactive sexual desire disorder (HSDD) in women. S1 Biopharma is evaluating partnerships, collaborations and out-licensing deals that will enable the company to rapidly advance its sexual dysfunction franchise as well as to accelerate the path to commercialization for its drug candidates in the U.S. and internationally. For more information, visit http://s1biopharma.com/ or follow S1 Biopharma on Facebook or Twitter (@s1biopharma).
- Laumann, E.O. Paik, A. Rosen, R.C. The epidemiology of erectile dysfunction: results from the National Health and Social Life Survey (1999)