Pretomanid - Approved for Highly Drug-Resistant Tuberculosis

Highlights :

• Pretomanid conditionally authorized by European Commission for the treatment of adults with extensively drug-resistant tuberculosis(XDR-TB) and multidrug-resistant tuberculosis (MDR-TB) who are treatment-intolerant or non-responsive
• Pretomanid is the first anti-TB which is developed by a not-for-profit organization called TB Alliance
• Pretomanid combined with bedaquiline and linezolid offers shorter, more efficacious, and easily manageable treatment for TB patients
• Favorable outcome of 90% was observed in Nix-TB clinical trial

Pretomanid is a new drug developed by the non-profit organization TB Alliance. The drug has been granted conditional marketing authorization by the European Commission (EC). Pretomanid is authorized in combination with bedaquiline and linezolid as a six month, all-oral for the treatment of adults with extensively drug-resistant tuberculosis (XDR-TB) or multidrug-resistant tuberculosis (MDR-TB) for the treatment of highly drug-resistant forms of tuberculosis (TB)who are either treatment-intolerant or non-responsive.

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What is the Three-Drug Regimen for Tuberculosis?

Combined treatment of bedaquiline, pretomanid and linezolid (BPaL) are commonly referred to as the BPaL regimen. BPaL was studied in a trial called Nix-TB in three sites in South Africa. The trial consisted of 109 people with XDR-TB and treatment-intolerant or non-responsive MDR-TB.

The Nix-TB trial showed a favorable outcome in 90% of the patients after about six months of BPaL treatment and post-treatment follow-up.

The results of the study are:

• 98 patients (90%) – a favorable outcome
• 11 patients (10%) – an unfavorable outcome

The unfavorable outcome was defined as either treatment failure or disease relapse during follow-up for six months after the end of the treatment. For only two patients, the treatment was extended to nine months.

Pretomanid has been clinically studied in 14 countries and contains application data on 1,168 people from 19 clinical trials.

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What is Pretomanid?

Pretomanid is a nitroimidazole drug. It belongs to a class of novel antibacterial agents.

TB Alliance developed Pretomanid since 2002. It has now received authorization as an oral tablet formulation as part of the BPaL regimen for the treatment of highly drug-resistant types of tuberculosis.

Pretomanid is the third new-anti TB drug approved by the Food and Drug Administration (FDA) in more than 40 years. It is the first drug to be developed and registered by a non-profit organization.

The drug has many attractive characteristics:

• Novel mechanism of action
• Activity in vitro against drug-resistant clinical isolates
• Activity as both a potent bactericidal and as a sterilizing agent in mice
• No evidence of mutagenicity in standard genotoxicity studies
• No significant cytochrome P450 interactions
• No significant activity against a broad range of Gram-positive and Gram-negative bacteria

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Why is BPaL Regimen Preferred?

Treatment of XDR-TB or treatment-intolerant and non-responsive MDR-TB is usually complex and lengthy. A combination of around eight antibiotics for 18 months or longer.

The World Health Organization (WHO) estimated a treatment success rate of 34% in XDR-TB and 55% MDR-TB before the introduction of BPaL.

BPaL regimen provides a shorter, more efficacious, and easily manageable treatment for patients, which are critical concerns at a time when health systems are being stretched to their limits.

BPaL regimen provides hope with nine out of ten patients achieving a negative culture result after six months post-treatment.

BPaL Adverse Reactions

The most common side effects of BPaL are:

• Neuropathy
• Nausea
• Anemia
• Vomiting
• Headache
• Dyspepsia
• Acne
• Decreased appetite
• Increased transaminases and gamma-glutamyl transpeptidase
• Rash
• Pruritus
• Abdominal pain
• Musculoskeletal pain
• Increased amylase

Distribution of Pretomanid

Pretomanid was granted Priority Review, Orphan Drug and Qualified Infectious Disease Product status.

TB Alliance has collaborated with numerous bodies throughout pretomanid’s development.

TB Alliance’s exclusive commercialization partner in Europe is Mylan. Mylan is a global pharmaceutical company which will market pretomanid.

“The authorization by the European Commission is another step forward in continuing to advance global access to TB treatments for patients in need,” said Mylan President Rajiv Malik.

Completion of long-term follow-up of patients in Nix-TB trial and completion of ZeNix trial is required for conditional authorization.

About Tuberculosis

• The bacteria, Mycobacterium tuberculosis causes tuberculosis (TB). The bacteria generally affects the lungs.
• Tuberculosis is generally spread from person to person through the air. Tuberculosis is preventable and curable.
• Tuberculosis mostly affects adults in their prime years, but all age groups are at risk.
• A total of about 1.5 million people died from tuberculosis in 2018. Globally, tuberculosis is one of the top ten causes of death
• Over 95% of TB cases and deaths occur in developing countries.

In summary, pretomanid has gotten conditional marketing authorization from the European Commission (EC) to treat highly drug- resistant tuberculosis.

References :

1. TB Alliance - (https://www.tballiance.org/about/mission)
2. FDA Approves New Treatment for Highly Drug-Resistant Forms of Tuberculosis - (https://www.tballiance.org/news/fda-approves-new-treatment-highly-drug-resistant-forms-tuberculosis)
3. Pretomanid - (https://www.newtbdrugs.org/pipeline/compound/pretomanid)
4. Tuberculosis - (https://www.who.int/news-room/fact-sheets/detail/tuberculosis)
5. TB Alliance and Mylan Announce Global Collaboration to Commercialize Investigational Drug Pretomanid as Part of Two Regimens to Treat Tuberculosis - (https://www.tballiance.org/news/tb-alliance-and-mylan-announce-global-collaboration-commercialize-investigational-drug)

Source-Medindia