Pharma companies are missing opportunities to make antibiotics available
Pharmaceutical companies are not registering new antibiotics where need is greatest. Older, clinically useful antibiotics are not widely supplied.
- New medicines cannot be made widely available until companies register them.
- Only 3 of 13 on-patent antibiotics are filed for registration in more than 10 countries where better access is urgently needed (out of 102 countries).
- Older antibiotics are not widely supplied to some low-income countries.
To reduce the threat of antimicrobial resistance (AMR), doctors must ensure that the right treatment is used to treat the infection in question. When shortages occur, doctors often resort to less optimal treatments, which poses an increased risk of AMR. The poorest countries tend to have a greater burden of infectious disease and higher rates of antibiotic resistance, making the need for better access to medicine all the more essential. Today’s ‘access gaps’ in relation to antibiotics increase the risk that effective antibiotics cannot be made available in future.
For new on-patent medicines, patent owners or their licensees must register them for sale in a country before they can be made widely available there. Best practice in this area is for patent owners to ensure new-product dossiers are prepared for access countries in parallel to major markets, to facilitate faster registration in those access countries.
Some older, off-patent antibiotics are still clinically useful but have become ‘forgotten’ – they are either no longer produced or are not being supplied. This may be because they are not profitable, because there is a lack of awareness of their clinical usefulness, or because there is lack of demand, as newer alternatives have become available. A list of ‘forgotten antibiotics’ was first defined by Pulcini et al in 2017.
What does the Benchmark analysis show?
The 2020 Antimicrobial Resistance Benchmark has tracked the efforts of large research-based pharmaceutical companies to register on-patent antibiotics. It looks at registration filings in 102 low- and middle-income countries – referred to as ‘access countries’ – where the disease burden is high and access to medicine is low. It has also evaluated whether companies, including generic medicine manufacturers, are supplying older ‘forgotten antibiotics’ to these access countries.
Based on these analyses, the Benchmark concludes that in general pharmaceutical companies are missing opportunities to make either new or older antibiotics available in access countries.
The companies assessed by the Benchmark have 13 new, on-patent antibiotics. Yet, only three have been filed for registration in ten or more access countries. For four on-patent antibiotics, the Benchmark found no evidence of registration filings in any access countries. Only one company reports pursuing licensing for any of these products (Otsuka, for delamanid (Delbyta®)). In conclusion, in dozens of countries, it is fair to assume that these on-patent medicines are not available.
When it comes to older, but still effective antibiotics, the numbers are similarly bleak. For this analysis, the Benchmark looked at whether companies are supplying any of the 30 defined ‘forgotten antibiotics’. The companies assessed have 24 such antibiotics in their portfolios. However, there is only evidence for 14 of these that they are being supplied to even one access country. Those 14 antibiotics tend to be ones that could be used for a broad range of infections. Half of the 14 forgotten antibiotics are on the World Health Organization Model Lists of Essential Medicines 2019 (EML).
How do companies’ practices compare?
The two most widely filed on-patent products in this analysis are: ceftolozane/tazobactam (Zerbaxa®) from Merck & Co, Inc, filed in at least 30 of the 102 access countries, and bedaquiline (Sirturo®) from Johnson & Johnson for multidrug-resistant tuberculosis, filed in 28 access countries. Antibiotics that can be used to treat multidrug-resistant tuberculosis account for six of the nine products that are being registered in any of the 102 target countries.
Most of the forgotten antibiotics are produced by multiple companies. For example, Pfizer and Teva all produce benzylpenicillin and supply it to at least one access country. Benzathine benzylpenicillin, a type of benzylpenicillin supplied by Pfizer, is the only antibiotic recommended to prevent mother-to-child transmission of syphilis. Shortages in many countries have contributed to an increase in syphilis globally. Mylan and Teva each produce 15 forgotten antibiotics, and report supplying more of them to access countries than other companies evaluated (six and five forgotten antibiotics respectively.
For new on-patent antibiotics, companies can prioritise filing for registration in countries with the highest burden of relevant infectious diseases. Registration can be accelerated and made more cost effective if companies prepare their registration dossiers during the product development stage, and then rapidly plug them into a joint assessment or other registration or prequalification mechanism.
There are disincentives to registration in some countries, such as limited local regulatory resources, low-volume markets, political instability or conflict, and economic sanctions. Although filing for registration is under the control of companies, an enabling environment could help reduce the burden and cost and therefore facilitate this step. For example, bedaquiline went through a procedure developed by WHO that aims to facilitate and accelerate national regulatory approvals.
To improve the availability of forgotten antibiotics and other older antibiotics, the priority is to ensure these medicines are still produced in sufficient volumes, and to put measures in place to make reliable supplies available within low- and middle-income countries. A role for non-profit medicine suppliers may also help pool demand. Colistin, for example, is a last-resort antibiotic to treat multi-drug resistant pneumonia, urinary tract infections and meningitis. It should be available and affordable in LMICs, provided there are good stewardship practices in place to prevent incidences of toxicity and reduce the risk of driving antibiotic resistance.