In the last decade, about 10 new antibiotics have been authorized in the United States of America, only two of these have a new mechanism of action and another 14 molecules are under development, whereas 25 years ago there were dozens.
In the race for cover, institutional advice is also welcome for companies, confirming that the situation is serious. In the United States, for example, there was great anticipation for the Guidelines of the Food and Drug Administration (FDA) issued in support of the reissue of the Prescription Drug User Fee Act (PDUFA IV). A series of addresses, to strengthen and promote the antibacterial pipeline, which had been solicited by the Infectious Diseases Society of America (IDSA).
The FDA's response is, for now, focused on acute bacterial sinusitis (ABS) and on how to design effective trials for the development of drugs in this direction. Over the next year, the regulatory agency is also expected to rule on acute bacterial otitis media, bacterial exacerbations of chronic bronchitis, and other infections.
Historically the FDA demanded non-inferiority studies, now the new guidelines recognize that in the majority of cases these studies are not appropriate, and indicate placebo-controlled trials as the optimal solution. However, the fact remains that, in the most serious cases, the placebo option is contraindicated and, therefore, we return to non-inferiority.
However, the standard recruitment procedures show some critical issues, in the case of bacterial infections, namely the difficulty of finding a sufficient number of participants for the rarer pathologies, the distance between the time necessary to evaluate the eligibility of the subjects and the need to start treatment as soon as possible, the impossibility of a certain diagnosis at the time of recruitment.
The diagnostic factor is the one on which many efforts are concentrated by small biotech companies and international groups such as GRACE (Genomics to combat Resistance against Antibiotics in Community-acquired LRTI in Europe), the European consortium that unites industries and academic institutions. In fact, TheraEDGE will start in January 2008, an integrated project lasting four years, with a total budget of 12 million Euros. Objective: to develop a molecular diagnosis kit capable of identifying the pathogens responsible for lower respiratory tract infections in just 20 minutes, while current methods of analysis require a few days.
Smaller companies, which can identify promising candidates on their own, however, need more resources to carry out trials and get to market; resources that have been in short supply since industry giants like Eli Lilly and Aventis left the field. IDSA sounded the alarm, and Congress increased the orphan drug grant from $25 million to $30 million in September in hopes that the stimulus will attract big pharma again.
In the meantime, the tactics for identifying new molecules are changing: the intensive screening of molecular libraries has not had the hoped-for success, so now we are returning to the past and to more traditional research methods. From evaluating natural samples, collected from around the globe, as Cubist Pharmaceuticals does, to remodeling old molecules to bypass resistance, as Wyeth is doing with tigecycline. Tigecycline was the progenitor of glycylcyclines, a semi-synthetic derivative of a tetracycline, effective against Gram+ and Gram- resistant to tetracycline. Both Cerexa and Johnson & Johnson, on the other hand, have a broad-spectrum cephalosporin in phase III with anti-
