This blog was written by Ankit Mahadevia, CEO of Spero Therapeutics, as part of the From The Trenches feature of LifeSciVC.
Infectious disease has had an ebb and flow relationship with our general awareness; epidemics such as Zika, Ebola, and SARS raise the profile of infectious disease in the public consciousness and then recede from memory. As they capture the headlines, these outbreaks mobilize financial and intellectual resources that are needed to treat these emergent and very important threats. As they recede from public memory, we still need to be vigilant about the threats that face us every day.
Framing the issue:
The problem of multi-drug resistant bacterial infections is ever present, and in particular the challenge of Gram-negative infections continues to pose a serious threat. Thirteen million patients in the G7 countries suffer from Gram-negative infections each year, and virtually all of these patients are hospitalized. Of these infections, 700,000 patients around the world each year die from multi-drug resistant infections. These strains are resistant to multiple (or sometimes all) available therapies, and mortality they cause is a gross underestimate given that many patients with serious chronic diseases such as cancer ultimately die of an infection. The problem is not just abstract; multi-drug resistant infections have cut short and altered the course of lives, and each of us can point to someone in our own lives or in the public eye that has fought or died from a serious infection. ( see here for some very moving patient stories). We are at a crossroad where we could lose control of common infections, thus making medical advances such as transplant, immunotherapies, and even common surgeries dangerous approaches to disease.
Inadequate response to date
A recent talk at the field’s scientific meeting framed the global mortality from MDR infections as the equivalent of 1700 jumbo jets crashing each year. Such a catastrophic event would undoubtedly drive a swift, public and private response. In contrast, what has been our response to the MDR catastrophe as drug developers over the last decade? We have stepped away, leaving health care professionals to use aging drugs that bacteria continue to evade.
Over the last twenty years, a range of companies have wound down their R & D efforts, driven by the limited flow of innovative therapies, a strict regulatory environment, and complexities in creating a global market for antibiotics (David Shlaes has a very insightful blog on pharma movement in the field here). In part because of this shift, we have not developed a novel mechanism for treating Gram-negative infections in over 30 years.
Major governments step up and drive a sea change in the field
Fortunately for public health, a concerted public/private response both in the US and globally has started to turn the tide. In particular, policymakers have done much to “push” new drugs to market. In the US and EU, there has been broad support for changes (captured within the GAIN Act in the US, and FDA and EMA guidance) to the regulatory environment that expedite the pathway to approval for select therapies with the potential to address serious unmet needs.
The importance of these changes cannot be overstated, both in terms of reducing historical barriers to drug development in the field and signaling that policy makers and regulators want to work with drug developers to actively solve the looming issue of antibiotic resistance. The global, multi-partisan support for additional incentives (such as the DISARM act in Congress and DRIVE-AB in Europe) further supports tailwinds for this field. In addition, public private partnerships such as BARDA, DTRA, and IMI-ENABLE have helped finance antibiotics development and kept programs moving towards approval even in tougher capital markets.
The net result has been a meaningful reentry into the space at the biotech and Pharma level. As an example of the power of policy to jump start the field, Spero Therapeutics was founded after the passage of the GAIN act to focus on novel Gram-negative treatments. If it were not for the new environment signaled by GAIN, Spero would not have been able to raise the capital to begin our development as a company. Our colleagues in Pharma (Roche, Merck as examples) and new entrants in biotech (Entasis, Arsanis, Macrolide, and others) likely would have had a tougher or no road forward as well.
We are not done yet: Future directions
We can’t rest here. Now that policy and (as always) great science have jump-started the field, the next step is to create lasting mechanisms to ensure a sustainable pipeline to treat serious infections. Microbes continue to evolve resistance against the few mechanisms we have against them; we need to keep evolving our approaches as well.
Along with incentives designed to push drugs to market, “pull” incentives will help ensure that new therapies that get to market are launched in a sustainable ecosystem. Prior therapies such as Cubicin and Zosyn, and recent approvals such as Avycaz support the important point that antibiotics that treat unmet need and demonstrate a differentiated antimicrobial spectrum have, and will continue to create value in the market even within the current system.
However, “pull” incentives can help further balance the need to create financial value with the need to encourage prudent use of new therapies. Incentives such as those contemplated by DISARM, legislation with bipartisan support that helps alleviate cost pressures hospitals face in using life-saving new antibiotics, are a good starting point. The time is now to implement this and other solutions supporting the field.
We now have the health care system’s attention about the problem, some early wins, and an opportunity to leverage this momentum to create a long-term, sustainable pipeline of therapies to stay one step ahead of the resistance issue. As one policymaker mentioned at a recent scientific meeting, it is time to stop talking and just get started.