I estimate a 92% probability that the World Health Organization (WHO) will prequalify moxidectin for the treatment of onchocerciasis before January 1, 2027. This forecast reflects confidence in the drug’s demonstrated efficacy, the alignment of prequalification with global health priorities, and the significant resources already dedicated to achieving this milestone.

Moxidectin’s strong clinical foundation makes its eventual prequalification highly likely. The drug is FDA-approved, with clinical trials showing it to be both safe and more effective than ivermectin in reducing skin microfilariae. Its longer-lasting effects and potential to lower treatment costs align with WHO’s goals of improving onchocerciasis treatment and accelerating elimination efforts. These advantages, combined with the unmet need for alternatives to ivermectin, position moxidectin as a compelling candidate for prequalification.

The WHO prequalification process is a rigorous pathway designed to ensure medicines meet global standards of quality, safety, and efficacy. It involves multiple stages:

1. Expression of Interest (EOI): The WHO publishes an EOI for the specific medicine and indication. MDGH has already engaged in this process for moxidectin.
2. Dossier Submission: The manufacturer submits a comprehensive dossier, including data on clinical efficacy, safety, and quality, as well as detailed manufacturing and quality assurance processes.
3. Technical Review: WHO evaluates the dossier through a technical review that includes assessment of clinical data, chemical composition, and quality control measures to confirm compliance with international standards.
4. Inspection of Manufacturing Sites: WHO conducts inspections of manufacturing facilities to verify they meet Good Manufacturing Practices (GMP).
5. Collaborative Process: WHO collaborates with regulatory authorities in countries where the medicine will be used, ensuring alignment on standards and recommendations.
6. Final Listing: If all criteria are met, WHO prequalifies the medicine, adding it to its official list. This step signals to governments, funders, and procurement agencies that the product is ready for large-scale deployment.

Prequalification is particularly critical for global health products like moxidectin, as it facilitates procurement by major donors (e.g., UNICEF, the Global Fund) and regulatory approval in endemic countries. Achieving prequalification is often a decisive step in ensuring widespread adoption and use.

Strategic funding and organizational capacity further bolster confidence. Medicines Development for Global Health (MDGH) has received substantial support, including a $637,549 grant from GiveWell, to address the additional clinical trials and regulatory requirements for prequalification. MDGH’s not-for-profit model ensures a focused approach to meeting WHO’s stringent requirements, leveraging its experience in neglected tropical diseases to navigate this process effectively.

However, risks remain. WHO’s unexpected demand for further clinical trials adds uncertainty to the timeline, and regulatory processes can be subject to delays. The need to address specific issues, such as Loa loa co-infection risks, may complicate the evaluation. These factors, while notable, are unlikely to prevent prequalification entirely, given the strong global health case for moxidectin and the resources dedicated to achieving this goal.

In conclusion, the alignment of moxidectin’s benefits with WHO’s priorities, combined with MDGH’s expertise and strategic funding, strongly supports a high probability of prequalification before 2027. My 92% forecast reflects both confidence in the process and an acknowledgment of potential delays, offering a balanced perspective on this critical development for global health.

Reasons for Optimism

• From what I can tell so far, the ongoing studies are going smoothly and MDGH is well-supported in the approval process.
• According to the WHO FAQ says that the median time to prequalification for a finished pharmaceutical product is ~200 days
• Per the same source, if the product is already approved by a stringent regulatory authority, the median time is generally 1-2 months, since approval does not required approval of the full dossier
• Moxidectin was approved in 2018 by the FDA (officially a "stringent regulatory authority" by WHO standards), but only for ages 12 and older.
• While MDGH hasn't gone through the WHO prequalification process themselves, it seems like they are working with the Tropical Disease Research division of the WHO, which presumably includes people deeply familiar with the process.
• The reasons for the additional studies on pharmacokinetics, safety & efficacy are not fully clear, but seem related to expanding the approval to children <12 and possibly developing an alternative formulation for children too young to safely swallow the pill in its current form.
• At least one study has been completed in 4- to 11- year old children, which MDGH plans to use to apply to the FDA for approval in younger ages.
• As of a few days ago, the Ghana Food and Drugs Authority approved moxidectin for river blindness in children as young as 4, enabling a community rollout program and adding another source of safety and efficacy data on children 4-11 years of age.

Reasons for Caution

• It's not entirely clear why the WHO wants the clinical trials it does for moxidectin, or how unusual this is compared to other drugs that go through the PQ process.
• It's not clear when the MDGH expects the invitation for the PQ process to occur or when they expect to submit their dossier. If there are political factors or safety concerns we aren't familiar with, that could easily affect the process.

It's difficult to estimate the exact time the process of prequalification will take at the WHO, but it seems quite likely it will happen before 2027.

The other parts of the process may not necessarily take all that much time (often less than a month each), but the two parts that can really delay it appear to be the 1) assessing the dossier (target timeline is 270 days) and 2) manufacturing site inspection (target timeline is 210 days). Together they might take approximately 16 months. Assuming the other parts of the process won't take very long, this should be feasible to accomplish by the deadline for the question (which is in 26 months from now).

It's worth noting that the target timelines are only estimates that are usually met, but not 100% of the time. The process may take somewhat longer in some cases, and usually less than that.

It's also worth mentioning that the assessing phase of the process could possibly be partially skipped (from 270 days to 100 days) since FDA already approved it for use once. Even without that, this seems more likely to resolve Yes than not, but especially in that case. I do not have the expertise to judge how likely that is to happen.

"Most importantly, depending on whether previous approval has been granted by another regulatory authority of sufficient maturity,⁵ WHO-PQ may conduct an abridged assessment, rather than a full assessment.⁶"

https://rethinkpriorities.org/publications/an-overview-of-who-prequalification-process-usage-and-potential-improvements

In any case, considering the internal assessment of 80% probability and having apparently plenty of time to spare until the deadline, I went a bit higher than the internal assessment. Perhaps there is some risk of getting stuck in the process that I'm not aware of, but from the publicly available information, it doesn't seem likely at all for it to take so long.