The risks of antibiotic research with Roche and Polyphor

The world urgently needs new antibiotic active ingredients. These are found, but rarely approved. The amazing stories of two Swiss companies offer an insight into a dilemma.

Antibiotic research is a hard plaster. If it would have been necessary for this long recognized and as a very threatening-qualified fact that it has been recognized by the World Health Organization, then it will be provided on Wednesday: At the West Civil Circle Court of West, the negotiation on the opening of the conflict of the Allschwiler Biotech company Spexis, formerly Polyphor, will take place.

The history of the company began thirty years ago with the resourceful brothers Jean-Pierre and Daniel Obrecht. With services in medication development for pharmaceutical companies, they earned the necessary money to continue their own research projects. The two brought it far.

Polyphor grew into a company with over 100 employees, most of them researchers. Their efforts for chemical production of molecules, which can imitate the biological effect of proteins, culminate in the development of a new technology, on the basis of which active ingredients for various indication areas could be developed. One of these active ingredients was particularly suitable for combating dangerous super bacteria.

Polyphor was specifically targeting the gram -negative germs. These are particularly clever to let antibiotic therapies run into nothing. The bacteria protect their cells with a double fat wall against antibiotics. Some have long been resistant to the most important antibiotic active ingredients such as carbapenemes or cephalosporins that keep all hospitals in reserve.

Polyphor technology was designed to produce an entire family of medication against such super germs. A first active ingredient with the name Murepavadin should make the pathogen pseudomonas aeruginosa out of it. This is on the WHO list of the 15 most dangerous bacteria, the combination of which « urgently » new antibiotics are needed.

Pseudomonas aeruginosa is a pathogen that typically triggers infections in the lungs of people who already suffer from serious illnesses and are very likely to die from such infections.

Big Pharma gives up, small bumps after

Polyphor was able to collect a lot of money and win renowned private and public investors at home and abroad for his projects. In 2013 the company closed a license agreement with Roche. The conclusion of the contract marked the return of the pharmamultis into antibiotic development.

In 1999 Roche left the business area after being considered « largely covered » for new antibiotics for new antibiotics, as a company spokesman summarized the motives at that time.

But in 2016 Roche withdrew from the joint development program with polyphor. The decision is « our assessment of the expected progress of the research project », was Roche at the time. Polyphor seemed to be able to get over the tart setback quickly. In 2018 there was a IPO. The company flowed another CHF 150 million. But Roche should be right. Murepavadin got stuck in the last stage of the clinical test.

The drug was tested on 150 patients who had infected with pseudomonas aeruginosa in the hospital and had to be artificially ventilated. Half received Murepavadin in combination with another antibiotic. The antibiotic treatment of the other half was carried out without the polyphorian substance. Too many Murepavadin patients got serious kidney problems. The side effects put an abrupt end to the attempt and, as it seems, the company soon.

High risks in the clinic

The story of polyphor and Murepavadin shows the central problems that make antibiotic research into a field with the highest risks: antibiotics generally have to be administered in large doses so that they have a real chance of killing all germs and preventing their reproduction in mutated, resistant form. The risk of side effects is correspondingly pronounced.

Combating dangerous, gram -negative hospital germs, which are already resistant to important broadband antibiotics, is particularly difficult and risky. Murepavadin’s purpose was to target one of the worst of these beetles. As obviously the benefits of such a narrow-band antibiotic may be, its disadvantages are so obvious: there is a risk that the medication leaves other germs involved in the infection undeveloped, so that the patient is in acute danger to life in the critical infection phase.