{"id":5500,"date":"2025-09-29T20:08:05","date_gmt":"2025-09-30T02:08:05","guid":{"rendered":"https:\/\/allphasepharma.com\/dir\/?p=5500"},"modified":"2025-09-29T20:08:09","modified_gmt":"2025-09-30T02:08:09","slug":"draft-fda-guidance-for-coccidioidomycosis","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2025\/09\/29\/5500\/draft-fda-guidance-for-coccidioidomycosis\/","title":{"rendered":"Draft FDA Guidance for COCCIDIOIDOMYCOSIS"},"content":{"rendered":"

\"\"<\/a>David Larwood, CEO of VFS, summed it up at the Cocci FDA workshop in 2020: \u201cWhen the market opportunity is limited, finding investment becomes the key issue\u201d.\u00a0 He mentioned other problems as well: \u201cVery low patient numbers for disseminated disease, prolonged therapy, NI trial design, definition of clinical outcome\u201d.[1]<\/a><\/p>\n

Clearly, the cost of developing a new drug has become prohibitively expensive and often requires partnering.\u00a0 It is also clear, that the business model for Cocci is a spreadsheet full of red numbers.<\/p>\n

In the world of infectious diseases, few indications are truly profitable by today\u2019s standards, and these are defined by oncology and autoimmune drugs; none can even come close to the revenue-generating potential of a Keytruda or Humira.\u00a0 There are exceptions, as always, like the latest generation of HCV drugs that were clearly novel, life-saving, and profitable.<\/p>\n

Big Pharma will partner with start-ups when their drugs meet certain criteria: true innovation, chance to be better, large addressable population, first to market, global market, long-term therapy not necessarily curative, reliable biomarkers for early derisking, feasible Phase 3 trials based on regulatory guidance, extension of indication.\u00a0 A long patent life with possibility for extension is also an important reason to invest.<\/p>\n

Take GLP-1 agonists: they pretty much have a checkmark behind all these criteria.\u00a0 The same goes for statins, PD-1 inhibitors, and allergy \/ asthma medications.<\/p>\n

A drug like nikkomycin (Nik Z) falls short in most of these categories:\u00a0 Few severe infections, small US and no global markets, soft outcome biomarkers and clinical benefit criteria, uncertain regulatory pathway, no remaining patent life.\u00a0 It would seem there is simply no way forward.\u00a0 Or is there?<\/p>\n

Just this month, in Sept 2025, FDA released a Draft Guidance for developing drugs for disseminated coccidioidomycosis. \u00a0Why for this indication, and why now?\u00a0 It\u2019s anyone\u2019s guess but there may have been some recent inquiries.<\/p>\n

A new FDA Guidance takes much uncertainty out of the development pathway and is always welcome.\u00a0 But this Cocci Draft Guidance is a bit of a downer: it does not introduce anything that we have not seen before; it follows the well-known Feel \/ Function \/ Survive (F\/F\/S) mantra.<\/p>\n

There is nothing wrong with the concept, but is it workable in this chronic disease?. Can any company ever enroll sufficient patient numbers for a NI trial with disseminated Cocci patients?\u00a0 Death is a relatively rare occurrence within a 1-2 years observation period, typical for such trials.\u00a0 How are we to assess the \u2018Feel\u2019 component?\u00a0 FDA seems to think that PRO tools could be developed to discern between \u2018stable disease\u2019, \u2018slowly progressive disease\u2019, and \u2018slowly improving disease\u2019.<\/p>\n

Agree with reservations: PROs can work in the context of Orphan drug development.<\/p>\n

Let\u2019s have a look at a recently completed Omadacycline Phase 2b trial in NTM infection, an equally slowly progressive disease.\u00a0 In 2023 Paratek announced that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) had recommended a positive opinion for orphan medicinal product designation.\u00a0 Results were posted recently indicating that it does not take a huge study to assess this orphan population.[2]<\/a>\u00a0 Only 66 patients were enrolled; clinical response, the primary efficacy outcome parameter, was based on a PRO, the NTM Symptom Assessment Questionnaire, at Day 84 Visit.<\/p>\n

Here is another example. To assess treatment response in ALS patients, Neurofilament Light (NFL) was felt to be a useful biomarker.\u00a0 Levels in CSF and serum correlated reasonably well with disease activity.\u00a0 While the FDA was ambivalent about accepting this biomarker, an Ad Board convinced Regulators to make an exception and grant \u2018conditional approval\u2019 for the drug.[3]<\/a>\u00a0 This helped a small start-up company execute a more definitive larger trial.\u00a0 When this study failed to confirm the earlier positive trend, the drug was withdrawn. Case closed.\u00a0 We feel this is the right course to take: give drugs a chance for rare diseases that cannot possibly be tested by the strictest of criteria, as long as there is no safety concern.<\/p>\n

In Cocci, we only have serology as a potential objective biomarker, but it is not very good at assessing \u00a0progression or improvement over time.\u00a0 Low sensitivity and specificity are issues, and so are reproducibility and accuracy.\u00a0 EIA, ID or CF tests are too coarse to serve as quantitative tools; textbooks still advise concurrent testing with a baseline sample in order to compensate for the biologic variability inherent with testing.\u00a0 What we need are tests that are sensitive to drug effect and\/or disease progression.<\/p>\n

In addition to a full roster of mycology experts, FDA invited leaders from pharma companies that were developing antifungals with activity against Cocci to the 2020 Public Workshop.[4]<\/a>\u00a0 Here is the list of companies and the fate of their projects 5 years later:<\/p>\n