Facing TB in Houston

FDA Fast-tracks GSK's Gonorrhoea Vaccine

News

Wikipedia

The FDA has given a fast-track designation to a gonorrhoea vaccine in development at GSK that could help turn the tide of the sexually-transmitted infection, which is on the rise around the world.

The coveted status is for GSK's NgG vaccine candidate, currently in a phase 2 trial in adults aged 18 to 50 considered to be at risk from infection with Neisseria gonorrhoeae, the bacteria that causes the disease.

Fast-track status is reserved for new drugs and vaccines that aim to treat or prevent serious conditions, for which there are few or no alternative therapies.

Gonorrhoea was diagnosed in 82 million people in 2020 and, according to World Health Organization (WHO) estimates, ranks high among the agency's infectious diseases of greatest concern, as it is rapidly becoming resistant to antimicrobial medicines. In the US alone, case numbers increased 118% between 2009 and 2021, to reach more than 710,000.

Some gonorrhoea infections have become untreatable with all seven main antibiotic classes, so there is a pressing need for effective vaccines that could prevent infections in the first place. Crucially, getting gonorrhoea once doesn't protect patients from re-infection.

An effective vaccine for N. Gonorrhoeae has eluded researchers for decades, mainly because they have targeted structures on the bacterial envelope that evolve rapidly, making it hard to find an antigen mix that has protective efficacy across different strains.

GSK's NgG shot is based on generalised modules for membrane antigen (GMMA) technology, consisting of outer membrane vesicles (OMVs) that are released from the bacteria during its growth and contain a range of antigens. GMMAs have attracted a lot of interest for their potential to sidestep the envelope variability issue.

Typically, GMMAs have to be engineered so they can be produced in sufficient quantities for vaccination, as well as to strip out any potentially harmful components, like endotoxins.

NgG is now in the phase 2 portion of the phase 1/2 study involving approximately 750 healthy adult subjects in the US, the UK, France, Germany, Spain, Brazil, the Philippines, and South Africa, with a readout expected in 2025.

Meanwhile, some research has found that vaccines against N. Meningitidis, designed to protect against meningitis – including GSK's MenB shot Bexsero – may also offer partial protection against gonorrhoea.

An investigator-led study reported at the recent Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, involving at-risk gay and bisexual men, found there was a 50% reduction in cases after two doses of Bexsero, although small numbers of patients were involved.

Bexsero is being tested in a phase 3 trial to see if it can prevent gonorrhoea in gay and bisexual men, with results due next year, but a shot more tailored to N. Gonorrhoeae itself could offer more protection and find wider use.

The potential impact on public health for a vaccine even with limited efficacy could be significant, according to a modelling study published earlier this year in the journal BMC Public Health.

Routine vaccination of 14-year-olds with a vaccine that offers just 31% protective efficacy could reduce infections by 50,000 cases over 10 years, adding another dimension to the benefits of protecting against invasive meningococcal disease.

Another company working on a dedicated gonorrhoea vaccine is Dutch biotech Intravacc, which secured almost $15 million in funding from the US government last year to advance its Avacc 11 OMV-based shot, which is currently still in preclinical development.

GSK Antibiotic Gepotidacin Clears Phase 3 Gonorrhoea Trial

GSK has reported topline results from a phase 3 trial of its novel antibiotic gepotidacin that could spell the end of a decades-long drought in new oral therapies for gonorrhoea.

In the EAGLE-1 trial, two oral doses of gepotidacin proved to be just as effective as standard combination therapy with intramuscular ceftriaxone plus oral azithromycin in resolving uncomplicated urogenital infections with Neisseria gonorrhoeae, the bacteria that causes gonorrhoea.

Gepotidacin was non-inferior to ceftriaxone/azithromycin at achieving a microbiological response at the 'test-of-cure' clinical visit, which takes place between three and seven days after treatment starts.

Gonorrhoea was diagnosed in 82 million people in 2020 and, according to World Health Organization (WHO) estimates, ranks high among the agency's infectious diseases of greatest concern, as it is rapidly becoming resistant to available antimicrobial medicines.

If untreated, gonorrhoea can lead to infertility in both men and women and other sexual and reproductive health complications, as well as increasing the risk of HIV infection. In the US alone, case numbers increased 118% between 2009 and 2021, to reach more than 710,000 - an alarming increase, given that some so-called 'super-gonorrhoea' infections have become untreatable with all seven main antibiotic classes.

Gepotidacin is aiming to become the first triazaacenaphthylene antibiotic to reach the market and is also in late-stage testing for uncomplicated urinary tract infections (uUTIs), another indication that has seen a dearth in new oral therapies. Positive data from two phase 3 uUTI studies – EAGLE-2 and EAGLE-2 – were reported last year.

It is one of two novel antibiotics that promise to provide much-needed new options for people with hard-to-treat gonorrhoea, along with Innoviva's bacterial type II topoisomerase inhibitor zoliflodacin, also chasing a first-in-class approval. In a phase 3 trial reported last year, zoliflodacin was also shown to be as effective as ceftriaxone/azithromycin at achieving microbiological cure.

Gepotidacin inhibits bacterial DNA replication by a novel mechanism of action and binding site, blocking two different type II topoisomerase enzymes, and has shown activity in the lab against multidrug-resistant strains of gonorrhoea and pathogens that cause UTIs, including Escherichia coli and Staphylococcus saprophyticus, according to GSK.

The pharma group, meanwhile, has another iron in the fire for gonorrhoea in the shape of its N. Gonorrhoeae vaccine NgG, which is in phase 2 development and was awarded fast-track status from the FDA last year.

There are real concerns that we could be entering a post-antibiotic era, where even minor infections can be enough to kill patients, and by some estimates antimicrobial resistance (AMR) could claim around 1.2 million lives per year globally by 2050 unless new drugs and other measures become available to control infections.

GSK is one of the few remaining big pharma companies carrying out R&D on new antibiotics, after a mass exodus from the category in the last few decades as companies struggled to get a return on R&D investment for drugs typically reserved for use when other therapies have failed.

The UK Government has made an effort to change that dynamic, launching a subscription payment model for new antibiotics that provides developers with a fixed annual access fee, regardless of how much is used to treat patients.

Chlamydia, A Silent Infection Causing Infertility In Young Adults

 Chlamydia is a sexually transmitted infection caused by a specific strain of bacteria known as Chlamydia trachomatis. [iStockphoto]

Chlamydia is a silent sexually transmitted infection that is so severe, in women, it causes blockage of fallopian tubes.

Lately, the disease has been raising eyebrows among fertility experts as the infection is highly observed among university students and young women of reproductive age.

Kenya Demographic Health Survey shows that Kenya's fertility rates have declined in the recent past, from 7.3 children per woman in 1960 to 3.3 in 2022.

Prof Koigi Kamau, a professor at the University of Nairobi in the Department of Obstetrics and Gynecology, says chlamydia is a sexually transmitted infection caused by a specific strain of bacteria known as Chlamydia trachomatis.

Chlamydia, he explained, is one of the bacteria that wreaks havoc on the female reproductive system because it infects the cervix, goes up to the fallopian tubes, and causes permanent damage. This is a major cause of infertility due to tubal blockage or tubal damage because of the inflammatory process.

Damage to the lining of the fallopian tubes makes it impossible to have the transportation of eggs for the fertilisation process.

Blocked tubes can also damage the fimbria (finger-like projections on the ends of fallopian tubes), which help in taking up the egg because fertilisation occurs in the fallopian tubes.

 Prof Koigi Kamau. [Courtesy]

"The bacteria can cause the tubes to narrow. It destroys the inner lining of the fallopian tube, which is what transports both the sperm and egg or ovum in order to facilitate the fertilisation process. If anything blocks the process, then it will cause infertility," says Prof Kamau.

He noted that the narrowing of fallopian tubes due to chlamydia because of inflammation and attachment (fimbria phimosis) is also the same with gonococcus (bacteria that causes gonorrhoea).

According to the fertility expert, infertility due to tubal damage is the most common, with nearly 80 per cent, chlamydia being the leading cause. Other causes of infertility include gonorrhoea, and infections as a result of unsafe abortions, endometriosis, and adenomyosis.

Prof Kamau explains that chlamydia is dangerous because its growth is insidious (slow) and imperceptible (not easily detected). Most patients are diagnosed at an adverse stage.

"Unlike gonorrhoea, when the pain comes, it is severe and therefore easy to look for attention," says Prof Kamau.

Immunological tests can detect the antigens (components of chlamydia), but they do not necessarily detect active disease.

"Chlamydia has been marked by mystery, yet it is extremely common, but it is married by the fact that its effects are insidious until tissues get attached together. It often blows up in society without announcing its presence," he says.

---