On August 14, the FDA approved the anti-TB drug pretomanid, only the third new drug for tuberculous (TB) in almost 50 years. Pretomanid’s developer, TB Alliance has become the first not-for-profit organization to both develop and register an antibiotic. The approved label provides for the use of pretomanid as part of a combination regimen with bedaquiline (Janssen) and linezolid (Pfizer), for the treatment of adults with pulmonary extensively drug-resistant TB (XDR), or treatment-intolerant or nonresponsive multidrug-resistant (MDR) TB. Pretomanid is the first-ever US FDA-approved drug for XDR-TB. The TB Alliance, which is dedicated to finding faster-acting and affordable drug regimens to fight TB, operates with the support of an extensive list of government and philanthropic organizations.
Powerful new results from this new therapy
According to the World Health Organization, TB kills 1.6 million people a year, about 500,000 of whom suffer from drug-resistant strains of the disease. Common TB treatments are ineffective for patients with XDR-TB. The standard of care for patients with this extreme form of the disease can include a combination of eight drugs for 18 months or more. But the drugs can come with serious side-effects, such as deafness, and up to two-thirds of patients with XDR TB are not expected to survive.
In a clinical trial for extensively drug-resistant (XDR) TB and treatment-intolerant or nonresponsive multidrug-resistant (TI/NR-MDR) TB, approximately 90 percent of patients receiving this newly-approved regimen recovered after six months of treatment—almost three times the success rate of prior treatment options. This groundbreaking work also resulted in the award of a tropical disease priority review voucher and sets the stage for a new approach to creating the next-generation of antibiotics for neglected diseases like TB.
Certara’s participation in this program
Certara is honored and humbled to have participated in this novel development program providing scientific support to the TB Alliance and the Bill & Melinda Gates Foundation during the development and regulatory filing processes. Certara contributions included population pharmacokinetic (PK) modeling, QTc (cardiac safety) modeling and analysis, PK/PD (pharmacokinetic/pharmacodynamic) modeling and related dataset construction in support of early decision-making and the regulatory submission.
Peer reviewed publications have already resulted from the contributions [1, 2, 3], with other manuscripts in process.
 Population Pharmacokinetics of Anti-Tuberculosis Agent Pretomanid, by David H. Salinger1, Vishak Subramoney1, Daniel Everitt2 and Jerry Nedelman2 (1Certara, Inc., 2TB Alliance) https://www.ncbi.nlm.nih.gov/pubmed/31405856
 Long-term Effects on QT Prolongation of Pretomanid, Alone and in Combinations, in Patients with Tuberculosis, by Hanbin Li1, David H. Salinger1, Daniel Everitt2, Mengchun Li2, Angelo Del Parigi2, Carl Mendel2, Jerry R. Nedelman2 (1Certara, Inc., 2TB Alliance) https://aac.asm.org/content/early/2019/07/23/AAC.00445-19
 Daily Dosing for Bedaquiline in Patients with Tuberculosis by David H Salinger1, Jerry R Nedelman2, Carl Mendel2, Melvin Spigelman2, David J Hermann3
(1Certara, Inc., 2TB Alliance, 3Bill and Melinda Gates Foundation). Publication pending-Antimicrobial Agents and Chemotherapy. This paper proposes a simplified dosing regimen for bedaquiline (a regimen partner with pretomanid), now being tested in two follow-up trials.
Certara is a Mission Driven Organization
About 6 weeks ago, we shared the launch of Certara Global Health and the expansion of our work with the Bill & Melinda Gates Foundation. Today’s news is another example of our contribution to achieving equity in health for all people worldwide.
In fact, in the past year or so, our contributions to global health have included:
- Certara’s collaboration with Medicines Development for Global Health (MDGH) on its new drug approval for moxidectin for treating river blindness, a neglected tropical disease. Like today’s news of this new TB treatment, MDGH was awarded a tropical disease priority review voucher, which was recently sold to Novo Nordisk so that MDGH can continue to develop treatments for neglected diseases.
- Certara’s scientific support to Siga for the development of TPOXX (tecovirimat), the first drug with an indication for treatment of smallpox. Siga is focused on providing solutions for unmet needs in the health security market that comprises medical countermeasures against chemical, biological, radiological, and nuclear (CBRN) threats, as well as emerging infectious diseases. Our work on dosing for TPOXX can be found here.
Though the World Health Organization declared smallpox, a contagious and sometimes fatal infectious disease, eradicated in 1980, there have been longstanding concerns that smallpox could be used as a bioweapon. According to the FDA, “This is the first product to be awarded a Material Threat Medical Countermeasure priority review voucher. Today’s action reflects the FDA’s commitment to ensuring that the U.S. is prepared for any public health emergency with timely, safe and effective medical products.”
- The selection of Certara by the Centers for Disease Control and Prevention (CDC) to develop a technology platform to strengthen the agency’s death investigation and surveillance systems (press release can be seen here). The technology we are creating will aggregate disparate data in a secure and private structure to facilitate decision-support analysis, visualization, and reporting of toxicology and other key drug-induced death information to address the drug overdose crisis in this country.
- Under contract to the Australian Government, Certara drafted a report and plan, entitled “Medical Countermeasures Initiative: National Capability Audit 2017” https://www.dst.defence.gov.au/sites/default/files/publications/documents/Medical%20Countermeasures%20Initiative%20Summary.pdf. This audit, and reports building from it, provides a framework for Australia to prepare and contribute to the global efforts in medical countermeasures product development.
Triple Bottom Line
The triple bottom line (TBL) is a concept which broadens a business’s focus on the financial bottom line to include social and environmental considerations. While today’s news and the examples shared above provide a clear example of Certara’s TBL commitment, our work every day in support of the development and patient access to safer and effective therapies underlies our mission.