DAV132 is a first-in-class product designed to inactivate antibiotics circulating in the colon and disrupting the gut microbiome. DAV132 has already been demonstrated to be safe and to effectively preserve the intestinal microbiome of healthy volunteers and patients in multiple clinical trials without impacting the clinical efficacy of antibiotic treatments.
DAV132 is primarily developed in cancer patients for whom antibiotic use is both life-saving and life-threatening:
DAV132 is the world most advanced product protecting against the clinical consequences of intestinal microbiome dysbiosis.
During antibiotic courses, a fraction of the drug remains in the intestinal tract. These active antibiotic residues progress to the colon where they kill numerous bacteria and lead to a profound disruption of the intestinal microbiome of patients. The microbiome balance is disturbed: several bacterial populations are erased while some proliferate. Microbiome disruption, called dysbiosis, is a long-lasting consequence of antibiotics intake and patient’s microbiome can remain disrupted for months.
In the late ileum, cecum and colon, DAV132 delivers a non-specific adsorbent which irreversibly captures antibiotics, before they can significantly alter the microbiome.
DAV132 adsorbent is encapsulated in a specific drug delivery system (smart coating) patented by Da Volterra that permits its targeted delivery in the lower gastro-intestinal tract. That way, DAV132 prevents antibiotic-induced disruption of the intestinal microbiome without interfering with antibiotics and/or other drugs’ efficacy.
DAV132 is regulated as a drug in the USA and its development plan was validated by the FDA in Pre-IND and Type C meetings. In Europe, due to its unique mechanism of action, DAV132 is regulated as a medical device and obtained a first CE mark in 2015.
Effect of antibiotic treatments taken without DAV132 in patients with hematologic malignancies
Patients with hematologic malignancies such as leukemia, myeloma or lymphoma receive numerous courses of antibiotics during the neutropenic phases that are induced by their cancer treatment. These massive and prolonged antibiotic treatments lead to an important disruption of their gut microbiome resulting in the occurrence of life-threatening complications such as severe infections, cancer relapse, delayed recovery, all ultimately leading to a poor quality of life and reduced survival (Peled et al. N Engl J Med. 2020). This is even more true for patients who receive a transplantation and for whom the perturbation of the microbiome also increases the occurrence and severity of Graft-versus-Host Disease (GvHD) (Taur et al. Blood. 2014).
Protecting the microbiome of hemato-oncology patients is essential to increase their chances of survival. DAV132 is the world-first product capable of preventing the life-threatening gut microbiome disruption in patients with hematologic malignancies.
The MICROCARE Phase 3 study is currently ongoing to evaluate the safety and clinical benefits of DAV132 in patients with hematologic malignancies. More details about the MICROCARE study below.
Effect of antibiotic treatments taken without DAV132 in cancer patients treated with immune checkpoint inhibitors
Cancers are traditionally treated with surgery, radiation and/or chemotherapy, with limited results. In recent years, a new approach has emerged and revolutionized cancer treatment: immunotherapy, which boosts patient’s own immune system response to help fight cancer. Immune checkpoint inhibitors (ICIs) are considered to be one of the most promising types of immunotherapy as they have shown unprecedented efficacy in several types of cancer.
Because cancer patients are particularly vulnerable to infections, they rely on antibiotics for their treatment. The medical community has been aware of the deleterious impact of antibiotics on the intestinal microbiome for many years. In the past 2 years, above 50 independent studies and 7 meta-analyses (Lurienne et al. J Thorac Onco. 2020; Cervesi J et al. ESMO Virtual Congress 2020) have shown that, by altering the microbiome, antibiotics may severely reduce the efficacy of ICIs and consequently the survival of cancer patients. As cancer care and antibiotics go together, it is impossible for physicians not to prescribe antibiotics and leave patients vulnerable to life-threatening infections. To ensure that cancer patients do not have to choose between the efficacy of their cancer treatment and the management of complications related to their disease, it is necessary to protect their gut microbiome from antibiotics, thus keeping their microbiome healthy.
By protecting the intestinal microbiome of cancer patients treated with ICIs and antibiotics, DAV132 will improve their survival.
A Phase 2 study is currently in preparation to evaluate the safety and clinical benefits of DAV132 in cancer patients for which antibiotic-induced dysbiosis is life-threatening.
Da Volterra announced positive top-line results from a Phase 2 clinical trial (named SHIELD) evaluating DAV132 in patients receiving fluoroquinolone antibiotics.
SHIELD was a multicenter, randomized, parallel-group comparative trial in which 260 patients were recruited in 4 European countries (Germany, Romania, Bulgaria, and Serbia). The study was designed to investigate the safety and efficacy of DAV132, taken during antibiotic treatment, to protect the intestinal microbiome. The patients enrolled had a median age of 71 years and 96% of them had at least one chronic comorbidity. They received oral or intravenous fluoroquinolone antibiotics for the treatment of lower respiratory tract infections, complicated urinary tract infections or for prophylaxis of febrile neutropenia.
The study met its primary endpoint and demonstrated positive results: