Preventive Biologics May Aid the Antibiotic Resistance Crisis

The antibiotic resistance crisis poses a threat to modern medicine. Antibiotic-resistant infections have become alarmingly common, and experts warn that if nothing is done we could face a future where minor injuries and routine surgeries carry deadly risks.

Society needs a paradigm shift in how infections are managed. New technology that now makes it possible to develop low-cost, scalable preventive biologics may be part of the solution.

The Challenge: No Incentive for Investors to Fund Novel Antibiotics

A big driver of the crisis is the broken economic incentive for new antibiotics. Developing a new antibiotic is costly, slow, and complex—no less so than any other drug. But unlike many other drugs, new antibiotics must compete with inexpensive generics. Worse, doctors rightly worry about further expanding resistance, so prefer to keep the new products in reserve. This is understandable, but an unintended side effect is low sales volumes.

This combination is commercial suicide. Low pricing power and limited sales have bankrupted every independent company that has tried to launch a novel antibiotic in recent years. Not surprisingly, investors have noticed and redirected their capital to other opportunities. It is nearly impossible to raise new equity funding for antibiotic development today.

This is what generates the economic paradox: New antibiotics are urgently needed and the societal costs of not having new antibiotics available are already significant, but because of broken economic incentives, few people are actually working to fix the problem.

Preventive Drugs Solve the Paradox by Making the Market Bigger

Preventive drugs may offer an economically viable alternative. To understand how this might be, consider the fact that most drugs today are administered after disease strikes. Preventive drugs are instead taken beforehand. This yields many economic benefits, especially improved outcomes for patients (eg, avoided pain, costly complications, and missed work) and cost savings for the health care systems (eg, obviating costly treatments, hospitalizations, and surgeries).

Unfortunately, small-molecule antibiotics cannot be used preventively due to ugly adverse effects. Prophylactic antibiotics also risk spreading resistant genes to other bacteria (the so-called “bystander resistance” problem).

Biologic drugs are different. They are much larger—usually protein molecules thousands of times larger than a typical antibiotic drug molecule. This makes it easy to precisely target the bad, disease-causing bacteria. This specificity reduces or eliminates off-target risks and bystander effects, making the drug safer for the patient and society as a whole.

Until recently, though, high manufacturing costs limited biologic drug technology to diseases treatable with small doses. A typical dose of a monoclonal antibody drug, for example, is less than 50 milligrams. They are also typically administered intravenously in a hospital or infusion center, which poses a significant cost in its own right.

However, recent breakthroughs in cell and protein engineering now make it possible to make and deliver, at very low cost, the much larger amounts of monoclonal protein needed to directly dose surfaces like the gastrointestinal (GI) tract, nasal passages, and skin. This allows drug developers to create biologic drugs for highly prevalent diseases that are more cost sensitive—including antibiotic resistant infections.

The approach has many advantages. For example, oral biologic drugs can be delivered as pills, obviating the need for needles or IV infusions. This improves access and avoids the costs and risks of needle administration. Also, the mucosal tissues of the GI tract and nasal passages are the ones most commonly attacked by infectious agents, so concentrating the drug delivery there is expected to be more effective than injecting it somewhere else. As a side benefit, protein therapeutics are too large for intact systemic absorption, so direct delivery to mucosal tissues also enhances safety by focusing on limiting the drug’s exposure to non-diseased tissues.

Together, these benefits amount to an entirely new class of medicines that never existed before. Fortunately, society seems to be primed for rapid adoption due to several major trends unfolding in the health care system today.

The Opportunity: Preventive Biologics and Recent Health Care Trends

The Self-Care Revolution

In recent years the “self-care” revolution has been driving structural changes in the consumer health care market. More and more consumers embrace the idea of taking proactive steps to maintain their health, particularly through the use of over-the-counter products that enable them to self-manage minor health concerns. This trend is part of a broader shift in health care that emphasizes prevention and wellness rather than reactive treatment.

Encouraged by patient advocacy groups and facilitated websites like Google and WebMD, this trend now extends to complex, serious disease like C difficile infection, inflammatory bowel disease, and cystic fibrosis. The tradeoffs are debated, but it’s a rare patient who doesn’t seek medical advice before leaving the clinic or pharmacy.

Preventive biologics will fit well into this new world where patients are accustomed to being proactive about their own health, just like they do today with statins, sunscreen, and (arguably) the new GLP-1 medicines for diabetes and weight loss.

The Expanding Role of Pharmacists in Preventive Care

The shift toward preventive care also complements the expanding role of pharmacists within the health care system. Pharmacists in many states now have the authority to prescribe medications for various conditions, including minor ailments, chronic disease management, travel health, vaccinations, and contraception.

Further expanding their authority complements the self-care trend because these medical professionals are far more accessible to the community than most other providers. This makes them ideally positioned to reign in some of the more “creative” ideas generated by the internet and coax patients instead toward proven remedies.

In this context, the superior safety and convenience offered by oral biologic drugs are essential to maximizing access.

About the Author

Brian Finrow, JD, is founder and CEO of Lumen Bioscience, a clinical-stage biotechnology company in Seattle.

Putting Pharmacists and Patients Back in Control of Drug Purchases

A third important trend is the rise of direct-to-consumer (DTC) pharmaceutical sales. Striking recent examples are Eli Lilly’s “Lilly Direct” platform for their obesity drug tirzepatide (Mounjaro; Eli Lilly) and Mark Cuban’s Cost Plus Drugs online pharmacy. Many patients are surprised to learn that they can sometimes get their medicines directly from such companies at a lower price than the traditional insurance co-payment route. This surprise and engagement may have also led to the current Federal Trade Commission lawsuit against the much-loathed pharmacy benefit manager (PBM) industry.

It is likely that mail-order pharmacies will never be the main way most patients get their medicines—the in-person role of the pharmacist is too important. But the DTC phenomenon does show that many consumers are demanding the freedom to access treatments that suit their individual health goals, and better price transparency. Pharmacists have always been the most important actors in counseling patients about their medicines, and this is likely to grow even more important.

Case Study: C difficile Prevention

C difficile offers a compelling example of how preventive biologics can impact public health. This terrible bacterial infection is one of the most common hospital-acquired infections and is usually caused by gut-flora disrupting antibiotics. Recurrent infection is common because the same agent used to treat the infection—antibiotics—is the very same thing that causes it. The CDC lists C difficile as a top antibiotic resistance threat.

Preventive biologics like the investigational drug LMN-201 (Lumen Bio) are being developed to address the problem by preventing infection rather than treating it after symptoms emerge. It is an oral biologic drug, delivered in a capsule, and its preventive effect is mediated by 4 monoclonal proteins. Three of these proteins neutralize the bacterial toxin that cause human disease (TcdB); the fourth is an enzyme protein that degrades the cell wall of the bacterium itself. All 4 proteins are far larger than the 2-kilodalton cutoff commonly cited as the upper limit for intact systemic absorption; and all 4 show specificity for the bacterium or its toxin.

Manufacturing LMN-201 to FDA standards is cheap and scalable, so it could conceivably be priced affordably enough to be used to prevent all C difficile infections—including the primary cases caused by antibiotics originally prescribed for unrelated infections—not just the high-risk recurrent infections like the C difficile preventatives on the market today. The benefits extend far beyond the patient, as reduced infection rates can also lessen the strain on health care resources, resulting in cost savings for the entire health care system. The fact that most C difficile cases now emerge in the community rather than hospitals means that more and more patients will be coming to pharmacies for relief.

Conclusions

Preventive biologics offer a fresh idea for resolving the antibiotic resistance crisis—one that stands to benefit everyone: patients, the health care system, and public health at large. In this way, shifting our emphasis from infection treatment can help generate sustainable, affordable health for everyone.