Tackling Rising Resistance: Combatting Infectious Diseases

The field of infectious diseases presents numerous challenges and unmet needs, but one issue stands out as particularly concerning: drug resistance. Overutilization and prolonged usage of antibiotics contribute to the development of drug-resistant bacteria, necessitating the development of new treatments. Spero Therapeutics, a biotech company based in Cambridge, is at the forefront of addressing multi-drug resistant (MDR) bacterial infections. By focusing on innovative approaches and novel therapies, Spero aims to combat drug resistance and meet the urgent needs of patients.

Ankit Mahadevia, CEO of Spero Therapeutics, emphasizes that two factors drive drug resistance: overutilization of antibiotics and prolonged usage. To delay the onset of resistance, it is crucial to choose appropriate populations for antibiotic use and employ them judiciously. Recognizing the importance of developing new antibiotics to stay ahead of bacterial resistance, organizations like CARB-X have emerged to support research in this field. CARB-X received a substantial funding boost of $250 million in 2016 from sources such as the Welcome Trust and the National Institute of Allergy and Infectious Diseases (NIAID). This funding aims to accelerate the collection of clinical data, attract outside investment, and foster progress in combating drug resistance.

CARB-X, part of Boston University, serves as a biopharmaceutical accelerator, aiding companies in their efforts to combat drug resistance. Kevin Outterson, CARB-X’s executive director, highlights the longstanding research efforts by academic groups in antimicrobial resistance. However, challenges on the business side, such as intellectual property and capital formation, have hindered the development of new antibiotics. Outterson emphasizes the urgent need for a long-term infrastructure and maintenance strategy, as bacterial resistance begins to emerge as soon as antibiotics leave the laboratory. The more antibiotics are used, the more their effectiveness degrades, necessitating a proactive maintenance approach.

Supported by CARB-X, Spero Therapeutics is actively addressing unmet needs in the infectious disease space. Their lead candidate, SPR994, is currently in Phase 1 trials and has the potential to be the first oral carbapenem approved in the United States and European Union. SPR994 focuses on oral Gram-negative antibiotics, aiming to prevent hospitalization or aid the transition of patients from the hospital to their homes. Mahadevia points out the increasing resistance rates of these drugs in both community and hospital settings, emphasizing the need for new oral Gram-negative agents.

Spero’s Potentiator Platform, featuring SPR741 and SPR206, targets Gram-negative bacteria prevalent in hospital settings and requires intravenous (IV) therapy. By advancing their pipeline, Spero expects to transition from a Phase 1 company to a Phase 3 company within the next 12 months. This progress holds the potential to address the urgent need for effective treatments against deadly Gram-negative infections.

Drug resistance poses a significant challenge in the field of infectious diseases. However, companies like Spero Therapeutics, supported by initiatives like CARB-X, are actively working to address this issue. By developing innovative therapies and focusing on unmet needs, Spero aims to combat drug resistance and provide effective treatment options for patients. With promising candidates in their pipeline, Spero Therapeutics is poised to make a substantial impact in the fight against multi-drug resistant bacterial infections, bringing hope to patients and healthcare professionals alike.

In the realm of infectious diseases, the current treatment approach relies heavily on hypothesis-based testing by clinicians, leading to empirical treatment with broad-spectrum antimicrobials. However, this methodology often results in wasted time, money, and the potential for developing resistance. It is evident that better diagnostic methods are needed to address these issues. Rapid diagnostic tests have gained significant traction in hospital settings, opening the door for the adoption of more targeted treatments in the market. As a result, the industry is shifting towards evidence-based, diagnostic-driven targeted anti-infectives, as explained by Vu Truong, the CEO of Aridis, a biopharmaceutical company specializing in infectious diseases.

Knowing the precise pathogen causing an infection empowers physicians to make informed decisions about treatment options. Physicians faced with this knowledge will likely choose a targeted therapy over a broad-spectrum antibiotic. Consequently, the rise of precise diagnostics is expected to replace conventional empirical therapies with evidence-based, diagnostic-driven targeted anti-infectives, improving patient outcomes and reducing the development of antibiotic resistance.

One of the significant obstacles in effectively addressing infectious diseases lies in the current reimbursement model. In the United States, for in-patients, antibiotics fall under the hospital’s Diagnosis-Related Group (DRG) bill, which is a bundled payment within Medicare. This payment covers various components such as the bed, operating room, nursing, and consumables, encouraging hospitals to economize on antibiotic costs. In the outpatient market, the perception of antibiotics as inexpensive poses a primary challenge. David Martin, chairman at Xyphos, highlights the stark comparison between the cost of oncology treatments and antibacterials, shedding light on the discrepancy in pricing and societal attitudes towards life-saving drugs.

Xyphos, which emerged from the split of Avid Biotics into two companies, is focused on CAR-T cell therapy, while Pylum remains dedicated to bacterial diseases. James Knighton, CEO and co-founder of Xyphos, acknowledges the challenges of attracting major investors in the infectious disease space. The market capitalization of companies with Phase 3 products in this field is notably lower than those in the CAR-T space. This discrepancy poses challenges for companies seeking funding and highlights the need for greater recognition and support in the infectious disease sector.

Several proposed solutions aim to address the unattractive reimbursement models in the infectious disease space. Nima Farzan, CEO of PaxVax, a leading vaccine company specializing in infectious diseases, suggests potential approaches. On the “push” side, various organizations can fund development efforts. On the “pull” side, options such as forward-purchase agreements or award mechanisms can be considered. Priority Review Vouchers (PRVs) were successful for a while but have become less effective due to their expanded availability and decreased value. To incentivize the development of novel antibiotics, market entry awards could be granted to companies, alleviating the pressure to sell in large volumes.

Improving diagnostic methods and overcoming reimbursement challenges are crucial for advancing the field of infectious diseases. The shift towards evidence-based, diagnostic-driven targeted anti-infectives holds the potential to revolutionize treatment approaches and mitigate the development of antibiotic resistance. Addressing the reimbursement model is equally vital, with proposed solutions focusing on funding mechanisms and innovative incentives to support the development of novel antibiotics. By embracing these changes, the infectious disease space can make significant strides towards better patient care, effective treatment options, and long-term sustainability.

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