LB-27. 10 x '20 Progress: Development of New Drugs Active Against Resistant Gram-negative Bacilli
Session: Poster Abstract Session: Late Breaker Posters
Saturday, October 22, 2011
Room: Poster Hall B1
Background: Infections caused by resistant bacteria, especially the “ESKAPE” pathogens, continue to increase in frequency and cause significant morbidity and mortality.  The lean pipeline for novel antimicrobial (AM) drugs to treat drug-resistant gram-negative bacilli (GNB) is a cause of justifiable alarm.  In a 2009 survey, no AM with a purely gram-negative spectrum had reached phase 2.  We now report on the pipeline for new therapies for these potentially life-threatening organisms.

Method: Literature review, clinical trials registries, interviews with pharmaceutical leaders.

Result: We found 9 IV compounds active vs. resistant GNB in clinical development:  one beta-lactamase inhibitor (BLI) combination in phase 3 study of complicated UTI (cUTI); 6 compounds in phase 2 studies of ABSSSI (1), cUTI (4), and/or cIAI (3), see table.   In addition, some promising compounds are in Phase 1 or preclinical development. We found no ongoing studies of HABP/VABP.  Only 3 compounds demonstrated a novel mechanism of action.

 

Product (Company)

 

Class

Status

1

CXA-201 (CXA-101 + tazobactam, Cubist)

BLI combination

Phase 3 (cUTI)

2

ACHN-490 (Achaogen)

Aminoglycoside

Phase 2 (cUTI)

3

CAZ-104 (NXL-104/ceftazidime, Astra Zeneca/Forest)

 BLI combination

Phase 2 (cUTI)

4

CPT-104 (NXL-104/ceftaroline, Astra Zeneca/Forest)

BLI combination

Phase 2 (cUTI and cIAI)

5

GSK052 (GlaxoSmithKline)

tRNA synthetase inhibitor

Phase 2 (cUTI, cIAI)

6

PMX-30063 (PolyMedix)

Peptide mimetic

Phase 2 (ABSSSI)

7

TP-434 (Tetraphase)

Fluorocycline

Phase 2 (cIAI)

8

BAL 30072 (Basilea)

Siderophore monosulfactam

Phase 1

9

MK-7655/Imipenem (Merck)

BLI combination

Phase 1

Conclusion: Our survey demonstrates tangible progress in development of new drugs that target infections caused by resistant GNB. The prognosis for an ever richer development environment will require progress in clarification of FDA regulatory clinical trial guidances (e.g., HABP/VABP, CABP), economic incentives for small and large pharmaceutical companies and ultimately a stable, robust, and sustainable R&D infrastructure.


Subject Category: A. Antimicrobial agents and Resistance

Helen Boucher, MD, FIDSA, Tufts Medical Center, Boston, MA, David Gilbert, MD, FIDSA, Department of Medical Education, Providence-Portland Medical Center, Portland, OR, Daniel Benjamin, MD, PhD, Duke University Medical Center, Durham, NC, John Bradley, MD, FIDSA, Pediatrics, University of California, San Diego, San Diego, CA; Rady Children's Hospital - San Diego, San Diego, CA, Barbara Murray, MD, FIDSA, University of Texas Medical School, Houston, TX, Brad Spellberg, MD, FIDSA, LABioMed, Torrance, CA; Harbor-UCLA Medical Center, Torrance, CA and George Talbot, MD, Talbot Advisors LLC, Saint Davids, PA

Disclosures:

H. Boucher, Merck: Adjudication committee, Consulting fee
Wyeth/Pfizer: DSMB member, Consulting fee
Durata: Consultant, Consulting fee
PolyMedix: Consultant, Consulting fee

D. Gilbert, achaogen: Consultant, Consulting fee
antiviral inc: Consultant, Consulting fee
merck: Consultant, Consulting fee

D. Benjamin, None

J. Bradley, None

B. Murray, Astellas: Grant Investigator, Research support
Johnson & Johnson: Grant Investigator, Research grant
Intercell: Grant Investigator, Research grant
Cubist: Grant Investigator, Research grant
Durata Therapeutics: Board Member and Consultant, Consulting fee
Rib-X: Board Member and Consultant, Consulting fee
The Medicines Company: Board Member and Consultant, Consulting fee
Pfizer/Wyeth: Board Member and Consultant, Consulting fee

B. Spellberg, Pfizer, Basilea, The Medicines Company, Achaogen, Glaxo Smith Kline, Eisai, Meiji: Consultant, Consulting fee
Cubist, AstraZeneca: Speaker (not on speaker's bureau), Speaker honorarium

G. Talbot, Achtelion, Basilea, Cempra, Cerexa, Cubist, Durata, FAB Pharma, JNJ, Kalidex, Meiji, Nabriva, Pfizer: Consultant, Consulting fee

See more of: Late Breaker Posters
See more of: Poster Abstract Session

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.