New ideas in the battle against resistant bacteria

When penicillin was developed in the 1940s, it revolutionized treatment for a broad range of infectious diseases – from meningitis, diphtheria and bacterial pneumonia to gonorrhea. Successive generations of antibiotics proved effective against other types of disease-causing bacteria. During the past decades, these “wonder drugs” have saved millions of lives and greatly expanded the average human lifespan around the globe.

The battle against deadly microbes, however, is far from over. The exposure of bacteria to antibiotics has helped many of these pathogens develop defense mechanisms. The number of these resistant strains has grown steadily, and hospitals remain with only a few effective antibiotics of last resort. Some infectious diseases have now become virtually untreatable, taking us back to the brink of the pre-antibiotic era.

While many pharmaceutical companies have retreated from this field to focus on chronic diseases and lifestyle drugs, Actelion has entered the fight with a new research group dedicated to meeting a medical need of alarming proportions.

Looking beyond conventional chemical structures

“From my perspective as a microbiologist and in light of the ever increasing resistance problem, this field of research should be a much higher priority,” said Wolfgang Keck, Head of Actelion’s Anti-Infectives Group. “Resistance is a fundamental and even inevitable problem: as we use antibiotics, we will lose them. The only solution to the current level of resistance is to think outside the box – to develop innovative compounds with completely new mechanisms of action. With compounds that work outside the framework of established resistance mechanisms, we can once again gain an edge on the pathogens.”

The Actelion Anti-Infectives group can draw on decades of combined experience in the pharmaceutical industry and its proven ability to develop new compounds. In just over one year, the 18-member team has already achieved promising results. “The secret of this success lies in our research team – a complementary blend of scientists from different disciplines who share a dedication to bringing novel innovative antibiotics to patients,” said Christian Hubschwerlen, Head of the Anti-Infectives Chemistry Group.

“From a conceptual point of view, we do not want to focus on specific bacteria but aim at new compounds covering therapeutic indication-specific spectra that will satisfy unmet medical needs,” added Wolfgang Keck. “Our two most advanced programs meet those criteria very well in vitro and in vivo. The first program focuses on an injectable antibiotic for severe hospital-acquired infections, covering therapeutically important Gram-positive pathogens (e.g. Staphylococcus aureus and Staphylococcus epidermis, Enterococci, Streptococcus pneumoniae) including their clinically relevant resistant forms and extends into the Gram-negative respiratory tract pathogens. The second program targets, with an injectable as well as orally available antibiotic, a broad range of community- and hospital-acquired infections such as those affecting the respiratory tract, skin and soft tissue. Our novel mechanism of action breaks through established resistances, providing full coverage of the Gram-positive pathogens and an even wider reach into the Gram-negative domain including extremely difficult-to-treat pathogens such as Acinetobacter.”

The potency of Actelion’s new antibiotic compounds has several clinically relevant aspects. “In many cases, we have achieved very high in vitro bactericidal results – killing 99.9% of the target bacteria within 24 hours,” explained Wolfgang. “Furthermore, the ability of our compounds to specifically address multiple targets results in a very low propensity for resistance development, which could buy us additional time before we need to develop yet another generation of antibiotics in this never-ending battle.”