पर्यावरण

Innovation in antibiotics research and development is urgently needed

There should be a movement to treat AMR as a national issue, pass policies and fund innovation. Such efforts would then have a cascading effect and allow funding to pour in from private investors

Antimicrobial resistance (AMR) is now recognised as an imminent health crisis ranked among the top 10 global threats affecting humanity. Most infections have now become untreatable owing to the emergence of “superbugs”. The looming danger of drug-resistant infections, the so-called “silent pandemic”, has thrown up major challenges for the healthcare sector warranting immediate action on a war-footing to curb this menace.

The discovery of penicillin was viewed as a much-needed remedy for the control of infections that were otherwise leaving humans with debilitating outcomes and high mortality rates. Antibiotics were considered as a huge blessing, providing the much-needed relief to humanity’s infection wreaked sufferings.

Surprisingly, Alexander Fleming had aptly warned of a clear possibility of antibiotic resistance following repeated use within society. A few decades later, multiple new antibiotics developed at a steady pace, with varying mechanisms of action. However, beyond the 1970s, there was a lull due to which the current antibiotic pipeline has run dry.

Looking back at what led to this dire situation, there seem to be a few obvious key indicators. There has been severe overuse, misuse, or abuse of antibiotics.

Shockingly, the rampant usage in livestock and agriculture compounded with inefficient waste management processes have led to adverse impact on the environment, including soil or aquatic systems which have now become extensively contaminated with drug-resistant bacteria.

On multiple fronts, the trajectory of antibiotic discovery has not taken off as expected.

It has been observed that there is lack of innovation in the area of AMR. Innovation through identification of new chemical classes with novel mechanism of action, possibly hitting more than one target may succeed in delaying resistance development.

However, target-based approaches have met with very little success as most of these pre-clinical candidates failed to show cellular activities due to either poor permeability or efflux liabilities.

Cell-based approaches, while succeeding in translating to cellular activities, do have to go past toxicity-related hurdles to qualify for the next stage and progress further into clinical development.

To add to the already difficult circumstances, most big pharma companies have exited this arena. A short course of antibiotic therapy meant less profitable returns unlike therapies for cancer or chronic life-style diseases which guarantees a major market share, often needing usage for an entire lifetime.

Recently, a slew of Public-Private-Partnerships have come forward and provided the necessary stimuli via grants and other support to facilitate discovery efforts and enable clinical development. These efforts — labelled as “push incentives” — need to be adequately complemented with ‘pull’ incentives, which guarantees revenue and sustenance to the antibiotic developers irrespective of the drug sales.

Current antibiotic discovery explorations have now shifted from big pharma to SMEs, a paradigm shift which while offering opportunities to innovate, allowing operations via flexible working models with quicker decision-making and rapid course correction options, need timely funding and support as research and development (R&D) explorations are risky and costs are quite prohibitive.

Other major hurdles that antibiotic innovators have to overcome, is the “science”, as it is extremely hard to identify new druggable targets for designing antibacterials.

Secondly, regulatory paradigms are tough to fulfil as high dosages are required for treating infections even if the duration is short. Thus, safety margins may prove to be quite difficult to achieve.

Thirdly, there are very limited funding options, and no private investment is available for clinical development. It’s a tough ask to keep the company afloat,  without completely diluting and still have some ownership and equity.

Finally, market forces are poorly organised. Even after you bring out the best molecule with half a billion dollar investment, there is no assurance of revenue for the company. For such a scenario, the government should step forward to pay for value and not by volume.

Another important issue which is specifically linked to antibiotics is that even if efforts are directed for optimal and affordable drug access to patients, we need to ensure that there is no overuse to avoid resistance development.

As far as potential solutions are concerned, it would be beneficial for all major regulatory bodies to come together, treat AMR challenge as equivalent to the climate change problem.

They should, as a combined force, work in a harmonised manner with a common agenda to support clinical trials, minimise duplication and lessen the burden on the developers without compromising safety.

Any enterprise which is seriously pursuing to solve AMR issues especially in a country like ours wherein the burden is very high, adequate support by the government is needed via funding for R & D, infrastructure and clinical development and provide incentives.

There should be a movement to treat AMR as a national issue, pass policies and fund innovation. Such efforts would then have a cascading effect and allow funding to pour in from private investors.

As a start-up, we feel we have strived hard to achieve a near impossible feat. We could assemble a global team with expertise in this area along with global suppliers, collaborators, investors etc, towards identifying a broad spectrum antibiotic after nearly 60 years and provide a one-stop solution for public health, war-fighter health and biothreats.

We took upon the challenge of AMR, a global health issue in India. As it is obvious, the R & D path for tackling AMR is very long and arduous. We feel that the areas to improve upon include a better understanding of some of the nuances of clinical development and for a sustainable working model, find quicker ways to close deals.

As the over-arching goal to resolve the AMR crisis,  “One Health” is viewed as a unifying multi-disciplinary solution wherein we ensure a safe ecosystem and optimal health for all life forms.

Such an initiative includes stewardship encompassing regulated antibiotic usage, surveillance, infection control and also extend measures to incentivise innovation of novel antimicrobial discovery along with alternatives to antimicrobials for non-human use.

Save humanity globally from this alarming health threat of AMR now.

Vasanthi Ramachandran  is Vice President – Collaborations in Bugworks Research India Pvt. Ltd and involved in leading efforts in Clinical Microbiology and external Collaborations within India and worldwide for both pre-clinical studies and clinical development

Views expressed are the author’s own and don’t necessarily reflect those of Down To Earth





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