With an estimated 87 million new cases a year, gonorrhoea affects every region of the world. If left untreated, it can have serious consequences for reproductive health and fertility, particularly in women. Pregnancy complications can include ectopic pregnancies, spontaneous abortions and stillbirths. Gonorrhoea also significantly increases the risk of contracting and transmitting HIV in men and women.

World Health Organization data shows alarmingly high levels of drug-resistance to the antibiotics used to treat gonorrhoea. In a survey of 77 countries, 97% reported instances of drug-resistance to commonly used treatment regimens and 66% to cephalosporins, the last options for treatment with a single drug.

N. gonorrhoeae is classified as ‘high priority’ on WHO’s list of pathogens representing the greatest threat to human health and most in need of new antibiotics.

GARDP’s STI programme outlines a research and development (R&D) strategy, developed with WHO and global experts to tackle drug-resistant STIs. It includes efforts to: develop a new treatment for drug-resistant gonorrhoea; investigate new combinations of antibiotics to treat STIs; and support the development of public health pathways to ensure sustainable access to treatment.

 

Objective, by 2023

  • Develop and deliver at least one treatment that will most impact on public health by ensuring it meets three criteria
    • – Works against drug-sensitive and drug-resistant  gonorrhoea
    • – Is suitable for integration into international and national STI treatment guidelines
    • – Can address urogenital and extra-genital infections

 

In 2017, GARDP published its R&D strategy in PLOS Medicine and entered into a partnership with Entasis Therapeutics to develop a novel, first-in-class oral antibiotic known as zoliflodacin. In 2018, results of a phase II clinical trial showed zoliflodacin to have high activity against drug-resistant gonorrhoea were published in published in the New England Journal of Medicine.

GARDP has started the clinical development plan for zoliflodacin and pharmaceutical development activities to secure a treatment formulation for use in trial sites and patients, with a focus on affordability.

In 2019, a multi-site phase III clinical trial is due to start in the Netherlands, South Africa, Thailand and the United States. This trial will support registration of zoliflodacin for uncomplicated gonorrhoea in high burden countries. In parallel, GARDP will carry out non-clinical activities such as microbiology surveys to ensure the product is effective against recent and geographically diverse strains of gonorrhoea.

 

More information



Target Product Profiles

  Ideal

Acceptable

Indication

First line treatment of uncomplicated, uro-genital gonorrhoea (sensitive and MDR)

First line treatment of extra-genital gonorrhoea (ano-rectal and oro-pharyngeal)

First line treatment of uncomplicated, uro-genital gonorrhoea (sensitive and MDR)

Activity against co-infecting STI pathogens

Chlamydia trachomatis  

Patient population

Adults and adolescents Adults and adolescents

Clinical efficacy

97% (95% CI, 95-100) 95% (95% CI, 90-100)

Activity against ESC and macrolide-resistant NG strains

Yes

Yes

Mechanism of action (target site, -cidal vs static; broad-spectrum vs narrow spectrum)

Bactericidal/static

Intracellular activity

No cross resistance

Bactericidal/static

Limited cross-resistance

Safety and tolerability

Safe in pregnancy and lactation

No patient monitoring required post treatment

Minimal outpatient monitoring required post treatment

Contraindications

None Pregnancy and lactation

Drug-drug interaction profile

None Minimal

Route of administration / formulation

Oral/IM, loose combination  

Dosing schedule

Single dose Multiple doses

Treatment duration

One day Up to 5 days

Stability

Heat stable, 3-year shelf-life in region 4 Heat-stable, 3-year shelf life

Cost (price /day of therapy)

Equivalent to current treatment regimens Oral/IM, loose combination

Time to patient availability

5 years 7 years
  Ideal Acceptable

Indication

First line treatment of uro-genital gonorrhoea (sensitive and MDR, complicated and uncomplicated)

First line treatment of extra-genital gonorrhoea (ano-rectal and oro-pharyngeal)

Treatment of chlamydia infections

First line treatment of uro-genital gonorrhoea (sensitive and MDR)

First line treatment of extra-genital gonorrhoea (ano-rectal and oro-pharyngeal)

Treatment of chlamydia infections

Activity against co-infecting STI pathogens

Chlamydia trachomatis, Mycoplasma genitalium Chlamydia trachomatis

Patient population

Adults, children and adolescents Adults, children and adolescents

Clinical efficacy

97% (95% CI, 95-100) 95% (95% CI, 90-100)

Activity against ESC and macrolide-resistant NG strains

Yes

Yes

Mechanism of action (target site, -cidal vs static; broad-spectrum vs narrow spectrum)

Unique mechanism

Bactericidal/static

Intracellular activity

No cross resistance

 

Bactericidal/static

Limited cross-resistance

Safety and tolerability

Safe in pregnancy and lactation

No patient monitoring required post treatment

Minimal outpatient monitoring required post treatment

Contraindications

None Pregnancy and lactation

Drug-drug interaction profile

None Minimal

Route of administration / formulation

Fixed-dose combination (FDC)  Co-packaged loose combination

Dosing schedule

Single dose Multiple doses

Treatment duration

Up to 3 days Up to 5 days

Stability

Heat stable, 3-year shelf-life in region 4 Heat-stable, 3-year shelf life

Cost (price /day of therapy)

Equivalent to current treatment regimens  

Time to patient availability

7 years 10 years