Excessive use of antibiotics has driven bacterial evolutionary mechanisms to the emergence of drug-resistant strains. The Food and Drug Administration (FDA) estimates that roughly 70% of bacteria causing nosocomial infections are no longer responsive to at least one of the drugs used for treatment. The list is growing and includes bacteria causing anthrax, gonorrhea, meningitis, tuberculosis and typhoid fever. Another concern is the emergence of methicillin-resistant Staphylococcus aureus (MRSA), which causes nosocomial infections in immune-compromised patients. On a worldwide scale bacterial and parasitic disease ranks second in the leading causes of death. With the emergence of resistant bacterial strains, the need for novel antibiotics is imperative. Better diagnostics are also needed to curb overuse of antibiotics and to promptly identify the emergence of resistant strains. Also, the importance of basic research in the identification of novel classes of antibiotics should not be overlooked, a recent example being the work published by Umland et al. identifying a new set of high-value potential antimicrobial targets for pathogenic Gram-negative bacteria, employing a new more clinically relevant approach.
Nevertheless, the big pharmaceutical companies are unwilling to invest in the development of more efficient antibiotics. The decline in antibiotic research is evident: 14 classes of antibiotics were introduced for human use between 1935 and 1968, and only five since then. The FDA had approved 29 drugs in the ‘80s (represented by 36 companies), but that number dropped to only nine after 2000. As of 2011 only seven large companies were still involved in the development of antibiotics, with Roche and Pfizer having closed their anti-bacterial R&D departments in 1999 and 2011, respectively. Contrary to chronic conditions, such as high cholesterol, diabetes, HIV or cancer, bacterial infections are treated in a very short period of time, usually not exceeding two weeks, and therefore generating less revenue while requiring similar investment and effort. Also, when an antibiotic of superior efficiency is approved, its use is restricted to avoid resistance emergence, further dulling the revenues. Adding the FDA’s regulatory hurdles that result in sky-high clinical trial costs, the reasons for the Big Pharma exit are fairly obvious.
The gap created by this exit, however, created vast opportunities for small biotech firms, such as Optimer Pharmaceuticals, which got approval for Dificid (fidaxomicin) in 2011, indicated to treat Clostridium difficile, a frequent nosocomial infection. Another example is that of Cubist Pharmaceuticals, with two products on the market: Cubicin (daptomycin), the prototype of a new class of antibiotics called lipopeptides, and Entereg (alvimopan). Even though the revenues per year are less than $1 billion, compared to tens of billions for drugs indicated for the treatment of chronic disease, such revenues are sufficient for the viability and growth of small biotech companies.
To reverse this decline in the antibiotics pipeline, Big Pharma has to be lured back into production, and this can happen only by revamping the business model, featuring higher–priced products and targeting smaller patient populations, according to experts at the Interscience Conference on Antimicrobial Agents and Chemotherapy meeting that took place last week in San Francisco. Such a move towards a value-based pricing model for novel antibiotics is necessary given the scarcity of antibiotics, especially for Gram-negative infections. An additional benefit is that increased pricing will restrict use and combat resistance. The emerging markets are another appealing reason for Big Pharma to resume its role in the development of antibiotics, although increasing concerns about overuse have begun to emerge. More specifically, India banned the sale of 92 over-the-counter antibiotics, and in China (as of August 1) doctors and pharmacists overprescribing specific antibiotics will no longer hold a license to prescribe the drug. Efforts in China have already resulted in a significant drop in the use of prescribed antibiotics (27.8% to 15% for outpatients and 80.5% to 58% for inpatients between 2006 and 2011).
Other initiatives involve the FDA’s priority reviews and additional five years of exclusivity, still much less than the 12 years enjoyed by biologics. Late last year, Europe switched gears, re-evaluating their guidelines for clinical trials to facilitate a more cost-effective process. On top of that, the Innovative Medicines Initiative fostered a partnership with five companies (Glaxo, Sanofi, AstraZeneca PLC, Janssen Inc. and Basilea Pharmaceutica Ltd) totaling €233m ($304m) contributed by both sides – a collaboration that is expected to improve efficiency in development. Whether the FDA and the European Medicines Agency will proceed in a common clinical program to ease submissions in both agencies remains to be seen, but it is clear that government bodies and the pharmaceutical industry need to work together towards the development of novel antibiotics.
Related research: Clostridium Difficile Infection (CDI) Therapeutics – Pipeline Assessment and Market Forecasts to 2019 This expert insight was written by Charalampos Valmas Ph.D, GlobalData's analyst for infectious diseases. For more information, or to request an interview, please contact our press team on the details below.
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