What Clinical Improvements Will Differentiate Emerging Therapies in a Market with High Unmet Need and Rising Use of Microbiome-Based Treatments?

Clostridium difficile infection (CDI) and Clostridium difficile-associated diarrhea (CDAD) are often the cause of nosocomial and antibiotic-associated diarrhea in hospitalized patients and other healthcare settings. Although standard-of-care antibiotics are relatively effective, the virulence of CDI is increasing, and standard antibiotic therapies are associated with high initial recurrence rates. Interviewed thought leaders report that severe and severe recurrent CDI/CDAD are areas of critical unmet need, and these physicians are hoping for superior clinical cure and recurrence rates from emerging CDI/CDAD therapies.

Questions Answered in This Report:

  • Key goals in the treatment of CDI/CDAD are to obtain clinical cure and lower the rate of recurrence. What are the key primary and secondary clinical trial end points with which new therapies for CDI/CDAD are evaluated? How do U.S. and European ID specialists weight efficacy, safety, and drug delivery attributes in the prescribing decision for severe and severe recurrent CDI/CDAD?

  • Oral vancomycin (ViroPharma’s Vancocin, generics) is the first-line therapy for severe CDI/CDAD and the major-market sales leader for CDI/CDAD. Fidaxomicin is the preferred second-line therapy and has lower recurrence rates than oral vancomycin. Emerging therapies must demonstrate an improvement in recurrence rate that is at least similar to, if not better than, that of fidaxomicin in order to gain favorable physician opinion. Given the low pricing and broad placement on hospital formularies, what degree of improvement over currently available therapies such as oral vancomycin do surveyed U.S. hospital pharmacy directors seek from new therapies on key clinical attributes for severe and severe recurrent CDI/CDAD? What clinical and cost burden challenges will drug developers need to overcome in order to capitalize on these CDI/CDAD populations of unmet need?

  • Clinical cure and recurrence rates in patients with severe CDI/CDAD are key drivers of physicians’ prescribing decisions and/or are the focus of drug development for new therapies for CDIs. 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 in the treatment of severe and severe recurrent CDI/CDAD?

  • Based on clinical data and thought-leader opinion, current fecal microbiota transplantation (FMT) therapy is the clinical gold standard in our Drug Comparator Model for severe and severe recurrent CDI/CDAD. What attributes do surveyed experts and interviewed thought leaders believe differentiate this therapy from competing current therapies and emerging therapies? Will any therapies in development challenge FMT therapy as the gold standard in 2019?


Attributes included in conjoint analysis-based assessment of target product profiles for severe and severe recurrent CDI/CDAD:

- Clinical cure rate in patients with severe CDI/CDAD.

- Clinical cure rate in patients with severe recurrent CDI/CDAD.

- Recurrence rate of CDI/CDAD.

- Time to resolution of diarrhea symptoms.

- Mode of delivery.

- Delivery burden.

- Price.

Attributes included in assessment of U.S. payers’ receptivity to new therapies for severe and severe recurrent CDI/CDAD:

- Clinical cure rate in patients with severe CDI/CDAD.

- Clinical cure rate in patients with severe recurrent CDI/CDAD.

- Rate of CDI/CDAD recurrence.

- Rate of rehospitalization for severe and severe recurrent CDI/CDAD.

Physicians surveyed: 60 U.S. and 30 European infectious disease (ID) specialists.

Payers surveyed: 21 U.S. MCO PDs.

Comprehensive List of Therapies Included in Our Research and Modeling:

Current Therapies

- Vancomycin (ViroPharma’s Vancocin, generics)

- Fidaxomicin (Merck’s Dificid, Astellas’s Dificlir)

- Fecal microbiota transplantation (FMT) (donor intestinal microbiota stool samples)

Emerging Therapies

- Surotomycin (Merck & Co.’s MK-4621)

- MK-3415A (Merck’s actoxumab + bezlotoxumab)

- Cadazolid (Actelion)

- RBX-2660 (Rebiotix)