Dear Colleagues! Today is Pharma Veterans Blog Post #157. Pharma Veterans shares the wealth of knowledge and wisdom of Veterans for the benefit of entire Pharma Community. It aims to recognize and celebrate the Pharma Industry Professionals. Pharma Veterans Blog is published by Asrar Qureshi on WordPress, the top blog site. If you wish to share your stories, ideas and thoughts, please email to email@example.com for publishing your contributions here.
Continued from last……
Rapid development of bacterial resistance to antibiotics is a serious challenge. While the pace of developing new drugs is slow, the resistance development is faster.
As mentioned earlier, smaller companies have taken up the task of developing new antibacterial drugs. The USFDA is also facilitating by way of early reviews and fast track registrations.
The antibiotics pipeline is still relatively small as compared to other therapeutic categories. It looks like that the major antibiotic groups such as cephalosporins, penicillin and quinolones are not yielding many new molecules.
Recent Discoveries and Approvals
“several antibiotics have been approved recently by FDA. In the area of Gram-positive infections, two new glycopeptides, Dalbavancin (Dalvance©, Xydalba©), Oritavancin (Orbactive©), and one new oxazolidinone Tedizolid (Sivextro©) offer alternatives to the already available choices. (1)
In the Gram-negative area, things are moving slower with only two new cephalosporin-beta-lactamase inhibitor combinations approved by FDA, Ceftobiprole (Zevtera©, Mabelio©) and Ceftolozane-tazobactam (Zerbaxa©), differentiating only in their activity on a molecular level of specific resistance mechanisms.” (1)
“A year ago, a group of scientists led by Dr. Kim Lewis, Director of the Antimicrobial Discovery Center at Northeastern University, reported a new antibiotic, teixobactin, able of killing several types of bacteria, including antibiotic-resistant strains of tuberculosis and staphylococcus (MRSA infections) without detectable resistance developing over time. Teixobactin is a small molecule antibiotic of a new class – the world’s first known medication capable of destroying ‘drug resistant’ bacteria.” (1)
“During the last 6 years the following small molecule antibiotics have received marketing authorization:
- ceftaroline for acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP);
- oritavancin for ABSSSI and CABP;
- telavancin for ABSSSI and CABP;
- dalbavancin for ABSSSI;
- tedizolid for ABSSSI;
- fidaxomicin for difficile colitis;
- ceftazidime-avibactam for complicated urinary tract infection (cUTI) and intraabdominal infection (IAI);
- ceftolozane-avibactam for IAI and cUTI.” (2)
Here is a snapshot of what is next in the pipeline. We may see all or some coming on to market in future. (3)
- VABOMERE ® by Medicines Company was approved by FDA in August 2017. It is combination of Meropenem with Vaborbactam for greater stability against resistant pathogens.
- BAXDELA ® by Melinta Therapeutics is currently in Phase III trial of Community Acquired Bacterial Pneumonia (CABP). It is Delafloxacin in both oral and intravenous injection forms.
- Lefamulin is by Nabriva Therapeutics AG for the treatment of Community Acquired Bacterial Pneumonia has gained attention by showing strong results and flexible dosing. It is Lefamulin
- Fosfomycin, the 45 years old antibiotic is back in news. Fosfomycin injection has been in a pivotal trial of patients with complicated urinary tract infection, including acute pyelonephritis. Fosfomycin injection (ZOLYD – Zavante Therapeutics) was found to be at par with piperacillin-tazobactam combination.
- Cefiderocol, the first siderosphere cephalosporin to reach late-stage development has a distinctive mechanism for penetrating Gram-negative pathogens, including some that are highly resistant to colistin; and carbapenem-resistant strains of Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae.
- Iclaprim, belongs to trimethoprim family and was developed to be more potent than trimethoprim. Unlike vancomycin, there is no evidence of nephrotoxicity with Iclaprim.
- Relebactam, is a new, novel beta-lactamase inhibitor which can be added to imipenem to make hitherto resistant strains, become more susceptible.
- Plazomicin, Omadacycline, Eravacycline were covered in the last blog post.
The list of new antibacterial drugs in not very heavily populated. But the pipeline is not dry either. We should hope to see further development, particularly in the new classes and new mechanisms of bacterial coverage.