MinervaX announces clinical trial of GBS vaccine for infections in newborns

Danish biotech company MinervaX has initiated a Phase I clinical trial with its Group B Streptococcal (GBS) vaccine candidate, GBS-NN, targeting pregnant women for the prevention of life-threatening infections in newborns.

GBS is responsible for 50% of life-threatening infections in newborns and affects 0.5- 3 in 1,000 such babies, depending on the geographical region. At any given time, some 15-25% of women are spontaneously colonised with GBS, and they run the risk of transmitting the bacteria both to their child in the womb, during birth and during the first months of life. GBS infection in the unborn child may lead to premature delivery or stillbirth, and GBS infection in the newborn child may result in sepsis, pneumonia or meningitis, all of which carry a significant risk of severe morbidity, long-term disability or death. Annually, GBS is responsible for some 8,000 infections in newborns, 800 deaths and 1,000 life-long disabilities in Europe and US.

Current GBS intervention, involving antibiotic prophylaxis during childbirth (known as intra-partum antibiotic prophylaxis or IAP) in women colonised with GBS or otherwise at risk of transmitting the bacteria to the newborn, has reduced the incidence of Early Onset Disease (EOD) occurring within the first six days of life by some 80% since its introduction in year 2000. However,

1) IAP has failed to fully eradicate EOD for a number of practical reasons and is not universally implemented in all countries;

2) IAP has no impact on GBS-induced premature delivery and still birth caused by infection of the unborn child;

3) IAP has no impact on Late Onset Disease occurring from seven days to three months of age,   where the burden of meningitis is highest. 50% of babies who recover from GBS meningitis have long-term sequelae, including brain damage, cerebral palsy, severe learning difficulties, hearing loss, and/or blindness;

4) IAP is currently only available in high-income countries and is unlikely to be implemented in low-income countries;

5) the efficacy of IAP is currently under threat from emerging antibiotic resistance in GBS, including the most commonly used antibiotics such as penicillin;

6) the widespread use of broad spectrumprophylactic antibiotic in birthing women has lead to an increase in antibiotic resistance amongst other bacteria also infecting newborns, particularly in preterm babies;

7) and finally, widespread antibioticprophylaxis in birthing women may negatively impact the developing intestinal microbiota of the newborn increasing the risk of eczema, asthma, ADHD and learning disabilities.

The development of an efficacious GBS vaccine for maternal immunisation capable of reducing this widespread use of antibiotic prophylaxis in birthing women and preventing more GBS infections both of early and late onset therefore addresses two significant medical needs. The annual market size for a GBS vaccine is expected to exceed 1 billion USD in Europe and US combined.

MinervaX believes its vaccine is likely to have superior characteristics compared with other GBS vaccine candidates in development. The latter are based on traditional capsular polysaccharide (CPS) conjugate technology. By contrast, GBS-NN is a single component, protein-only vaccine based on a fusion of two highly immunogenic and protective protein domains from selected surface proteins of GBS (N-terminals of AlphaC and Rib). Given the broad distribution of proteins from which the vaccine originates as well as cross-reactive proteins, it is expected that MinervaX’s single component vaccine will protect against up to 95% of GBS isolates.

The Phase I trial will enroll up to 310 healthy adult women in two parts. Part A will enroll up to 70 women to investigate safety and initial dose-escalation and Part B will enroll up to 240 women to further evaluate safety and confirm dose and regimen. The trial will take place in Belfast, Northern Ireland. In addition to important safety data, the trial will provide information towards defining an optimal dose and schedule for the vaccine as well as response rates, magnitude and duration of the immune response. Exploratory endpoints will include an assessment of the vaccine’s potential ability to protect women against spontaneous vaginal colonisation with GBS and provide preliminary data on the breadth of coverage of the vaccine (ability to neutralise different isolates of GBS).

According to Per Fischer, D.Phil., chief executive officer of MinervaX: “The initiation of the Phase I clinical trial represents a very significant milestone for the company, towards its goal of achieving preliminary clinical proof of concept by late 2016.”

The development of the company’s GBS vaccine candidate is funded partly by the EU FP7 NeoStrep project, and as Per Fischer added: “ The initiation of the clinical trial is also a tribute to the support offered by the EU FP7 program and a testament to the excellent collaboration and contribution of NeoStrep project partners.”

Group B Strep Support is the UK’s only charity dedicated to preventing group B Strep infections in newborn babies. Chief executive and founder of the charity Jane Plumb MBE welcomes the news that Phase 1 of the clinical trial has now begun.

“We are delighted that MinervaX is developing a group B Strep vaccine. Group B Strep is the most common cause of severe infection in newborn babies, although most of these infections are preventable. The UK’s prevention strategy has failed to reduce the rates of these infections for more than a decade.

A safe and effective vaccine is the ‘holy grail’ of GBS prevention as it could protect more babies from GBS infection than any other strategy, though is still years away. In the meantime, the UK needs to identify women carrying GBS late in pregnancy so that protective antibiotics in labour can be targeted at those who will benefit the most – the babies of women carrying group B Strep.”