AMV 100 (“Gynevac”, Lactobacillus platform)
The product Gynevac originated from the lactobacillus platform and was approved in Hungary in 1997 for the treatment of acute, subacute and chronic gynecological inflammations caused by bacteria and trichomonads and administered to over 200,000 patients over more than a decade. AmVac is currently working on the re-registration in Hungary based on current EU regulatory standards for the indication of bacterial vaginosis, with a view to achieving wider EU approval in due course.
Bacterial vaginosis (BV) is the most common cause of vaginal infection in women of childbearing age. Bacterial vaginosis is caused by an imbalance of naturally occurring bacterial flora of the vagina. Although BV is associated with sexual intercourse with a new partner, it is not considered a sexually transmitted infection. Studies have shown that approximately 29% of women in the U.S. are affected. Bacterial vaginosis is found in about 25% of pregnant women in the U.S. and approximately 60% of women who have a sexually-transmitted infections (STI) (source: AJOG, Dec-2013).
Up to 50% of women with BV can report no symptoms. Symptoms can however include:
- Burning on urination
- Itching around the vagina
- Abnormal/ smelly vaginal discharge
This condition increases the risk of:
- Secondary infections such as HPV (Human Papilloma Virus), HIV (Human Immunodeficiency Virus), Chlamydia Trachomatis, Herpes Simplex virus as well as infections following pelvic surgery
- Many pregnancy related complications such as pre-term delivery, miscarriage and post-partum endometriosis
- Pelvic inflammatory disease
- Failure of IVF
Although BV can clear up without treatment, it is advised that all women with signs and symptoms of BV are treated to avoid complications. BV treatment is especially important for pregnant women. Pregnant women who have had premature births or low weight babies should have a BV examination, even if there are no symptoms. It is also recommended that all women undergoing a hysterectomy or abortion should be treated for BV before their procedure, regardless of symptoms.
BV is most often treated with antibiotics which are generally effective in controlling the condition in the short term. However, antibiotic treatment is associated with:
- allergic reactions
- high recurrence rate of BV (up to 80% within 9 months)
- risk of antibiotic resistance
- other side effects
Because of this, a new, effective, sustainable treatment option would be very attractive.
Anticipated advantages of AMV100
- Full recovery of vaginal flora leading to long-term protection
- Low 5% recurrence rate within 9 months
- Highly effective relief from symptoms: 95% of patients report decreased symptoms and increased quality of life
- No significant side effects
AMV110 (Lactobacillus platform)
The AMV110 product, also based on the lactobacillus platform, successfully completed an open label Phase II clinical trial in Hungary involving approx. 100 patients with chronic prostatitis and benign prostate hyperplasia (BPH). Results were highly encouraging: 91% of patients reported decreased symptoms and increased quality of life based on an internationally accepted symptoms scoring system. No side-effects such as decreased libido or hypotension occurred.
Benign Prostate Hyperplasia
BPH is a common nonmalignant enlargement of the prostate gland affecting about 50% of men in their sixties and up to 90 % in their seventies and eighties, according to the National Institutes of Health, US. The potential market for BPH products is therefore huge.
BPH is associated with Lower Urinary Tract Symptoms (LUTS), most commonly straining/ hesitancy, urgency, nocturia, incontinence and incomplete emptying. These symptoms have a considerable negative impact on patients’ quality of life.
The pathophysiology of BPH seems to be complex. The following factors may be involved: age-related tissue modifications, hormonal imbalance (alterations, metabolic syndrome) and inflammation. Importantly for the hypothesized mechanism of action of AMV110, prostatic inflammation may represent an important factor in BPH development. Prostatic cells themselves are able to secrete inflammatory mediators which stimulate their own growth. Once the vicious circle has started, it appears that feedback controls (hormonal and cellular) can be overwhelmed and that prostate volume progressively increases. Large clinical studies confirmed a relationship between prostatic inflammation and benign prostatic hyperplasia.
Current treatments for BPH are depending on the severity of the condition and include:
- Watchful waiting (for very mild cases)
- Medical therapy (for example with alpha blockers and/ or 5 alpha reductase inhibitors)
- Surgical treatment (reserved for most severe cases)
Side effects of medical therapies can be significant (orthostatic hypotension, dizziness, fatigue, ejaculatory disorder, decreased libido, erectile dysfunction, etc.) and can limit treatment compliance, hence efficacy. Surgical interventions such as Trans Urethral Resection of the Prostate are also associated with significant side effects.
As with most chronic diseases, BPH is progressive, hence management of early BPH may help control prostate growth and LUTS progression. There is clearly a significant unmet need for a safe, well tolerated treatment for this condition.
Anticipated advantages of AMV110
- Long-term effect
- Significant symptom relief
- Excellent safety
- No undesired side-effects on blood-pressure or libido
AmVac expects AMV110 to have strong potential to outperform current treatments and extend BPH therapy to the group of ‘watchful waiting’ patients.
AMV401/ 411 (MALP-2 platform)
AMV401 is an adjuvanted vaccine for the prevention of seasonal influenza, which is particularly suited to the needs of the elderly. Preclinical efficacy studies are currently ongoing. AMV411 is an adjuvanted vaccine for the prevention of pandemic influenza.
Influenza is an acute infection caused by an influenza virus. Typical symptoms include high fever, chill, cough, pain and overall malaise. Although most people recover from influenza within a week, the disease can cause severe complications in certain risk groups requiring hospitalization and potentially leading to death. Risk groups include babies and children younger than age 2, elderly age 65 or older and patients with serious other diseases or debilitated immune systems. Furthermore, influenza has significant socio-economic impact. Epidemics often result in high levels of worker absenteeism and productivity losses.
Several vaccines against seasonal flu are available and although they can be effective in healthy adults younger than 65 there is significant room for improvement in the treatment of elderly and other risk groups.
Anticipated benefits of AMV401 & AMV411
- Potential for needle-free application (e.g. nasal spray)
- Potential for MALP-2-adjuvanted vaccines to demonstrate greater efficacy
- Strong potential to confer better protection to risk groups
- More efficient dosing
AMV602/ 611 (Sendai virus vector platform)
AMV602 is intended for the prevention of respiratory diseases caused by Respiratory Syncytial Virus (RSV). AmVac has already established initial proof-of-concept and is currently preparing Phase I clinical trials. AMV611 is a combined preventive vaccine against human Parainfluenza Virus Type 3 (PIV3) and RSV. AmVac has initiated preclinical studies for AMV611.
Respiratory Syncytial Virus
RSV is one of the most common causes of bronchiolitis and pneumonia in children and the elderly, and the number one cause of childhood hospitalization in the US, Europe and around the world. Nearly all children are infected with RSV at least once by the age of 2-3 years. The disease is particularly dangerous for premature babies, children with other health conditions and the elderly. Many children develop pulmonary disease and/or asthma from early infections that persists throughout adult life making them susceptible to re-infection.In addition, RSV is increasingly being recognized as a significant problem in certain adult populations. These include the elderly, persons with cardiopulmonary diseases, and immune-compromised hosts. Epidemiological evidence indicates that the impact of RSV in older adults may be similar to that of non-pandemic influenza.
RSV is very contagious. Inoculation occurs mainly through the eye and nose, rather than the mouth and infection may occur directly from a host or via droplets left on surfaces in the environment. RSV infections occur primarily during fall, winter, and spring.
According to studies, each year, on average, in the United States, RSV leads to
- 57,527 hospitalizations among children younger than 5 years old
- 100,000 to 126,000 hospitalizations among children younger than 1 year old
- 2.1 million outpatient visits among children younger than 5 years old
- 177,000 hospitalizations and 14,000 deaths among adults older than 65 years
Both the global burden of the RSV infection and its highly contagious nature highlight the need for a vaccine. The only current treatment that is specific to RSV is a monoclonal antibody with limited efficacy at high cost, thus, the treatment is mostly reserved for certain severe cases in high-risk groups.
Anticipated advantages of AMV602 & AMV611
- Potential to effectively prevent RSV- and PIV3-infections
- Particularly suited to the risk groups who need it most – potential live vaccine efficacy with dead-vaccine safety profile
AMV701 (Sendai vector platform)
AMV701 is intended for the prevention of infection with the Ebola virus. It is currently at candidate selection stage.
Ebola is an extremely lethal disease, caused by ebolaviruses. Initial symptoms include fever, sore throat, muscle pain, and headaches, generally within two days to three weeks after contracting the virus. The symptoms usually proceed to vomiting, diarrhea, and rash, while liver and kidney functions are reduced. The disease is characterized by strong bleeding both inside and outside the body, and carries a high death rate with fatalities typically occurring within one to two weeks from initial symptoms.
While the disease has historically been mostly incurring in Africa in short waves, it has spread across the world including to Europe and the US following recent outbreaks in 2014/2015. According to WHO commentary, “the Ebola epidemic ravaging parts of West Africa is the most severe acute public health emergency seen in modern times. Never before in recorded history has a biosafety level four pathogen infected so many people so quickly, over such a broad geographical area, for so long.” (source: WHO Media Centre, Sep-2014).
Infection control, isolation of infected and potentially infected people, and contact tracing currently are the major means to prevent the disease from spreading after incidence is reported; however, no specific treatment is currently approved in the EU or the US.
AmVac has developed a promising set of potential vaccine candidates against the disease, from which it is selecting a candidate for further evaluation.