Stakeholder Opinions: Sexually Transmitted Infections - The Silent Menace

Table of Contents

• ABOUT DATAMONITOR HEALTHCARE
  • About the Infectious Disease pharmaceutical analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Introduction
  • Scope and coverage of the report
  • Datamonitor Insight into the Sexually Transmitted Infections market
    • Sexually Transmitted Infections are widespread on a global scale, affecting several hundred million individuals every year. For example, chlamydia, the most common STI, is estimated to cause up to 100 million new infections per year, while the human papillomavirus (HPV), the most abundant sexually transmitted viral pathogen, causes over 500,000 annual cases of cervical cancer.
    • STIs predominantly affect individuals who engage in high-risk sexual behavior, comprising frequent change of sexual partners, multiple partners and unprotected sex. Thus, the peak incidence of most common STIs occurs in those aged 16-24 years, with the exception of syphilis, which affects older strata of the population in particular the MSM group.
    • In addition to potentially causing symptomatic disease following the primary infection, if left untreated, STIs can further lead to the development of severe complications. These include infertility in both sexes, while pregnant women can additionally pass on the infection prior to or during delivery, which may lead to sequelae such as blindness or lung damage in the newborn child. Moreover, increasing evidence supports a tight epidemiological link between STIs and HIV.
    • While bacterial and parasitic STIs can be cured with antibiotic therapy, viral STIs can be effectively managed but not eradicated. Consequently, there is little financial incentive for the development of post-exposure therapies for both bacterial and viral STIs. Therefore, current STI R&D activity focuses on the development of prophylactic vaccines for HSV-2 and HPV infection. However, the current political and social climate notably the controversy surrounding the use of STIs vaccines in young girls might initially hinder the uptake of any prophylactic STI vaccine.
    • Key metrics
• CHAPTER 2 SEXUALLY TRANSMITTED INFECTIONS: AN OVERVIEW
  • Overview of common STIs
    • Epidemiological trends
      • The asymptomatic nature of STIs leads to underreporting
      • STI incidence is widespread
      • Most STIs increase the risk for acquisition and transmission of HIV
      • 16- to 24-year old people and MSM are at highest risk of infection, while pregnant women are at highest risk for complications
      • Incidence and consequences of STIs differ between men and women
    • Disease management
      • Most patients are identified when they present with symptomatic disease, but these are a minority of those infected
      • The goal of therapy depends on the nature of the infecting agent
      • Bacterial and parasitic STIs can be cured with antibiotic therapy
      • The focus for viral STIs is on the development of preventative vaccination, as current therapies fail to eradicate the underlying infection
      • The benefits of preventative vaccination are best reflected by the dramatic effect of hepatitis B vaccination in reducing the hepatitis B incidence
      • Resistance to therapy currently affects mainly gonorrhea
      • The STI pipeline is scarce, mainly due to low unmet needs
• CHAPTER 3 CHLAMYDIA
  • Disease overview
    • Etiology and epidemiology
      • Chlamydia causes various diseases, the most common being the STI caused by Chlamydia trachomatis
      • Chlamydia is the most common STI worldwide
    • Disease progression and clinical manifestations
      • In women, chlamydia is the most common reason for infertility and ectopic pregnancies
      • Pelvic inflammatory disease is predominantly caused by chlamydia and gonorrhea
  • Disease management
    • Chlamydia can be effectively managed with curative antibiotic therapy
      • Prevention focuses on low-risk sexual behavior
      • Chlamydia diagnosis remains sub-optimal
      • Chlamydia can be cured with single-dose azithromycin
  • Future market outlook
• CHAPTER 4 GONORRHEA
  • Disease overview
    • Etiology and epidemiology
      • In the West, gonorrhea is commonly caused by genitourinary exposure
      • The second most common STI affects predominantly men
    • Disease progression and clinical manifestations
      • Untreated gonorrhea can lead to a range of complications in adults and to blindness in the newborn child
  • Disease management
    • Increasing resistance has been changing prescription practices
      • Prevention focuses on low-risk sexual behavior, although microbicides are currently being evaluated in the clinic
      • Three types of laboratory tests allow for correct gonorrhea diagnosis
      • The gold standard of gonorrhea treatment is single-dose antibiotic therapy
      • Increasing gonococcal resistance, especially to fluoroquinolones, has led to the preferred use of third-generation cephalosporins
  • Future market outlook
• CHAPTER 5 GENITAL HERPES
  • Disease overview
    • Etiology and epidemiology
      • Traditionally caused by HSV-2, genital herpes is now increasingly being caused by HSV-1
      • HSV is a ubiquitous disease and most commonly affects women
    • Disease progression and clinical manifestations
      • Following the primary infection, patients with genital herpes often suffer from recurrent disease episodes
  • Disease management
    • With curative antiherpes therapy representing an unrealistic goal, HSV R&D focuses on the development of a prophylactic vaccine
      • Partial prevention of HSV-2 transmission is currently achieved with Valtrex, while GSK's prophylactic HSV-2 vaccine Simplirix might prevent infection in the future
      • Sensitive methods allow for effective diagnosis
      • Antiviral therapy effectively controls, but does not cure, HSV infection
      • Valtrex (valacyclovir) is the current HSV market leader
  • Future market outlook
    • 2009: a blockbuster dies, a vaccine is born
      • Valtrex's and Famvir's patent expiries in the US are expected to lead to loss of value from 2009 onwards
      • GSK's Simplirix protects HSV-seronegative women from HSV-2 infection
      • Two therapeutic HSV-2 vaccines have recently entered Phase I clinical trial
• CHAPTER 6 GENITAL WARTS
  • Disease overview
    • Etiology and epidemiology
      • HPVs are a large family of viruses associated primarily with benign warts
      • HPV warts are the most common viral STI
    • Disease progression and clinical manifestations
      • Although most HPV infections are benign, infection with high-risk HPV types can lead to the development of cervical cancer
  • Disease management
    • HPV cannot be cured, but a prophylactic vaccine might soon reduce the incidence of cervical cancer
      • 2006 is likely to witness the launch of a first-in-class prophylactic HPV vaccine
      • A combination of methods is used for the diagnosis of genital warts, HPV DNA and cervical cell abnormalities
      • Treatment is not curative and consists in the destruction of warts
  • Future market outlook
    • The future lies in prevention through vaccination
      • Merck and GSK are currently developing preventative HPV vaccines
      • Gardasil versus Cervarix
      • Issues associated with STI vaccination
      • HPV vaccine market potential
• CHAPTER 7 SYPHILIS
  • Disease overview
    • Etiology and epidemiology
      • The great imitator
      • Recent outbreaks have led to an increase in syphilis cases, in particular in men who have sex with men (MSM)
    • Disease progression and clinical manifestations
      • Left untreated, late stages of syphilis can progress to cardiovascular and CNS disease
  • Disease management
    • If detected early, syphilis can be cured
      • Prevention relies on low-risk sexual behavior
      • Diagnosis is achieved through serology and microscopy
      • Penicillin G is the gold-standard cure for syphilis
• APPENDIX A
  • Bibliography
    • Journals
    • Epidemiology
    • Fact sheets
    • Press releases
    • Datamonitor reports
    • Websites
    • Miscellaneous
  • Report methodology
  • About Datamonitor
    • About Datamonitor Healthcare
    • About the Infectious Disease analysis team
  • Disclaimer
  • List of Tables
    • Table 1: Chlamydia, gonorrhea, syphilis, genital warts and genital herpes: key facts
    • Table 2: Developmental prophylactic and therapeutic STI vaccines
    • Table 3: STIs covered in this report
    • Table 4: Number of reported STI cases in the US
    • Table 5: Recommended treatment regimes for common bacterial STIs
    • Table 6: While genital herpes is managed with suppressive viral therapy, genital warts are removed using physical or chemical methods
    • Table 7: Commonly used antibiotics for the management of chlamydia
    • Table 8: Recommended treatments for the management of gonorrhea and gonorrhea/chlamydia coinfection
    • Table 9: HSV-2 prevalence in the seven major markets
    • Table 10: Antiviral therapies recommend for the treatment of first and recurrent episodes of genital herpes
    • Table 11: Valtrex has been approved for several different indications in the management of genital herpes
    • Table 12: Ongoing Simplirix trials
    • Table 13: Two therapeutic candidate HSV-2 vaccines are currently undergoing Phase I clinical trials
    • Table 14: Clinical diseases associated with the different HPV genotypes
    • Table 15: Genital warts can be removed using a range of physical or chemical methods
    • Table 16: Estimated prophylactic HPV vaccine peak sales
    • Table 17: Recommended treatments for the management of the various stages of syphilis
  • List of Figures
    • Figure 1: Epidemiological trends in STIs, UK, 2000-04
    • Figure 2: While bacterial and parasitic infections can be cured with antibiotics, the goal of therapy for viral infections is treatment or prevention of symptomatic disease
    • Figure 3: Common STIs can be caused by bacteria, viruses and parasites
    • Figure 4: Diagnoses and rates of selected STIs seen at GUM clinics, UK, 2000-04
    • Figure 5: In the US, chlamydia is the most abundant and fastest rising bacterial STI
    • Figure 6: Various biological mechanisms have been proposed to explain how STIs increase the risk for HIV infection and transmission
    • Figure 7: Population subgroups at higher risk of acquiring STIs
    • Figure 8: High-risk sexual behavior is the key risk factor for the high rates of STI transmission among young persons and MSM
    • Figure 9: More than half of all reported STIs in the UK in 2004 occurred in young persons aged 16-24 years
    • Figure 10: Estimated annual incidence of STIs in pregnant women, US
    • Figure 11: Acquisition of an STI during pregnancy can have serious consequences for the newborn child
    • Figure 12: The incidence of some STIs differs significantly between men and women
    • Figure 13: If left untreated, STIs can lead to long-term sequelae
    • Figure 14: Only a small proportion of those infected with an STI are diagnosed and treated
    • Figure 15: While bacterial and parasitic infections can be cured with antibiotics, the goal of therapy for viral infections is treatment of symptomatic disease
    • Figure 16: In the US, the incidence of acute HBV has declined steadily between 1990-2002, in particular in children and adolescents
    • Figure 17: Genital warts, gonorrhea and syphilis could benefit from therapeutic improvements
    • Figure 18: In 2004, 66% of reported chlamydia cases in the UK occurred in young people aged 16-24 years
    • Figure 19: If left untreated, chlamydia can cause serious complications, especially in women
    • Figure 20: Pelvic inflammatory disease PID is predominantly caused by untreated chlamydia and gonorrhea
    • Figure 21: Between 2000 and 2004, the number or reported chlamydia cases in the UK increased at an average annual rate of 11.1%
    • Figure 22: Reported cases of gonorrhea in the UK, 2004
    • Figure 23: In the UK, the number of reported gonorrhea cases has been decreasing since 2002
    • Figure 24: In the US, gonorrhea incidence has been falling since 1988
    • Figure 25: Failure to treat gonorrhea is associated with the development of serious complications
    • Figure 26: Gonorrhea can be diagnosed through three types of laboratory techniques
    • Figure 27: Gonococcal resistance has led to a frequent review of US treatment guidelines
    • Figure 28: In 2001, in Hawaii, gonococcal resistance rates were close to 20%
    • Figure 29: In the UK, in 2004 almost two-thirds of reported genital herpes cases occurred in women
    • Figure 30: Once infected with HSV, patients often suffer from recurrent episodes of genital herpes
    • Figure 31: Goals of antiviral therapy
    • Figure 32: Therapy for genital herpes can be either episodic or suppressive
    • Figure 33: Since its first launch in 1995, Valtrex has rapidly captured market share in the HSV/VZV antiviral market
    • Figure 34: Two key patent expiries are expected to lead to loss of value in the HSV/VZV market from 2009 onwards
    • Figure 35: Overview of completed Simplirix trials
    • Figure 36: In the UK, the number of reported episodes of genital warts cases has been increasing at an average of 2.8% since 2000
    • Figure 37: Initial visits to physician offices, US, 1990-2004
    • Figure 38: In the UK, in 2004, the number of reported cases of syphilis occurred predominantly in young persons aged 20-24 years
    • Figure 39: HPV genotypes most commonly associated with cervical cancer and genital warts
    • Figure 40: Factors that influence the choice of the treatment
    • Figure 41: Overview of Gardasil Phase III study presented at the Infectious Diseases Society of America (IDSA) annual meeting 2005
    • Figure 42: Comparison of Merck's and GSK's candidate HPV preventative vaccines
    • Figure 43: Potential positioning of developmental prophylactic HPV vaccines
    • Figure 44: The rising incidence of syphilis in the US is driven by increasing numbers of infections in men
    • Figure 45: In the UK, the number of reported syphilis cases has been increasing since 2000
    • Figure 46: In the UK, in 2004, the number of reported cases of syphilis occurred predominantly in men aged 25 and 44 years
    • Figure 47: Syphilis disease progression