The Alarming Scarcity of Treatment Options for These Pathogens Presents an Attractive Market Opportunity for Novel Antibiotics

The carbapenems are a class of potent gram-negative antibiotics that represent a last-line of defense for drug-resistant gram-negative infections (GNIs). However, the increasing prevalence and severity of infections caused by multidrug-resistant gram-negative pathogens, particularly carbapenem-resistant organisms (CROs), and the diminished commercial interest in developing novel antibiotics have resulted in a very limited and compromised CRO armamentarium characterized by agents with severe safety and tolerability risks. Public health officials and physicians alike are calling for immediate action and drug development to address this significant global public health concern. Pending legislation and other government-sponsored efforts, combined with an evolving regulatory landscape, are providing the framework to streamline and promote the development of novel antibiotics, including the FDA’s acceptance of nontraditional clinical development programs for investigational antibiotics intended for conditions for which there is high unmet medical need. The FDA’s recent approval of Merck’s Zerbaxa (ceftolozane/tazobactam) and Actavis/AstraZeneca’s Avycaz (ceftazidime/avibactam) and a promising late-stage pipeline (Tetraphase’s IV/oral tetracycline eravacycline, Achaogen’s next-generation aminoglycoside plazomicin, and The Medicines Company’s Carbavance [meropenem/RPX-7009]) will begin to address some of the clinical challenges in this market. Nevertheless, opportunity remains for effective therapies for GNIs due to CROs that can provide meaningful improvements in clinical cure rates and mortality rates without the risk of serious adverse events that characterize many current treatments in this segment of the antibiotics market.

Questions Answered in This Report:

  • Improved overall survival (lower mortality rates) and higher clinical cure rates are key goals in the treatment of GNIs due to CROs. What are the key primary and secondary clinical trial end points with which new therapies are evaluated? How do U.S. and European infectious disease (ID) specialists weight specific efficacy end points and other drug attributes in their prescribing decisions for GNIs due to CROs?

  • Improvements in microbiological eradication rates and in clinical rates in patient populations infected with CROs and agents associated with a lower propensity to cause nephrotoxicity are key areas of unmet need in this market, according to the insights of surveyed U.S. and European ID specialists. Which therapies in development for GNIs due to CROs are poised to fulfill these needs? What clinical and/or regulatory challenges must drug developers overcome in order to capitalize on these areas of unmet need? What degree of improvement over currently available therapies do surveyed U.S. hospital PDs seek from new therapies on key clinical attributes for which surveyed physicians indicate there is high unmet need?

  • Efficacy outcomes (i.e., survival and clinical response) evaluated in CRO populations and the rate of adverse events are key drivers of physicians’ prescribing decisions and/or are the focus of drug development of new therapies for GNIs due to CROs. What trade-offs across these and other clinical attributes are U.S. ID specialists willing to make when considering the use of emerging therapies for the treatment of GNIs due to CROs? Based on the trade-offs in price and performance across key drug attributes that U.S. ID specialists are willing to make, how do physician preference and prescribing likelihood vary across different target product profiles for GNIs due to CROs?

  • Following its launch in 2018, Achaogen’s plazomicin will emerge as the gold-standard therapy in our Drug Comparator Model because of its superior clinical profile over the key current therapies we evaluated. On what clinical attributes is plazomicin most differentiated from its competitors? Which current therapies are at greatest risk of being replaced by plazomicin and other promising emerging therapies?

Scope:

Attributes included in conjoint analysis-based assessment of target product profiles for the treatment of GNIs due to CROs:

- 28-day all-cause mortality (ACM) rate in patients with confirmed or suspected CRO infections.

- Clinical cure rate in patients with confirmed or suspected CRO infections.

- Microbiological eradication rate in patients with confirmed or suspected CRO infections.

- Propensity for adverse events in patients with confirmed or suspected CRO infections.

- Size of patient population for assessment of safety and tolerability.

- Formulation.

- Price.

Attributes included in assessment of U.S. hospital PDs’ receptivity to new therapies for the treatment of GNIs due to CROs:

- ACM rates in patients with GNIs due to CROs.

- Clinical cure rates in patients with GNIs due to CROs.

- Rates of serious adverse events.

- Dosing frequency and availability in interchangeable IV and oral formulations.

Physicians surveyed: 60 U.S. and 30 European ID specialists.

Payers surveyed: 20 U.S. hospital PDs.

Comprehensive List of Therapies Included in Our Research and Modeling:

Current Therapies

- Tigecycline (Pfizer’s Tygacil/Taigashiru)

- Colistin (JHP Pharmaceuticals’ Coly-Mycin M, generics)

- Meropenem (AstraZeneca’s Merrem/Meronem, Sumitomo Dainippon’s Meropen, generics)

- Amikacin (generics)

Emerging Therapies

- Ceftazidime/avibactam (Actavis/AstraZeneca’s Avycaz)

- Ceftolozane/tazobactam (Merck’s Zerbaxa)

- Eravacycline (Tetraphase)

- Meropenem/RPX-7009 (The Medicines Company’s Carbavance)

- Plazomicin (Achaogen)