{"id":1079,"date":"2014-10-16T16:15:22","date_gmt":"2014-10-16T20:15:22","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=1079"},"modified":"2014-11-10T22:27:07","modified_gmt":"2014-11-11T03:27:07","slug":"nikkomycins-are-finally-getting-some-respect","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2014\/10\/16\/1079\/nikkomycins-are-finally-getting-some-respect\/","title":{"rendered":"Nikkomycins Are Finally Getting Some Respect"},"content":{"rendered":"

Besides azoles, candins and the polyene class of antifungals there is not much to select from when it comes to systemic fungal infections.\u00a0 Until the recent arrival of voriconazole and posaconazole, infections caused by molds always required amphotericin B to control.\u00a0 Only for Candida several good treatments exist on the market, the fungistatic azoles and the fungicidal candins.<\/p>\n

For the endemic mycoses (histo, cocci, blasto) treatment options are still rather limited.\u00a0 Itraconazole remains a useful drug for severe or progressive forms of histo but the best therapeutic approach for cocci is less clear.\u00a0 In the absence of solid data supporting a specific antifungal or class, azoles, candins and amphotericin are all potential agents to be tried sequentially.[1]<\/a>\u00a0 There is no truly curative therapy as of yet and many patients relapse even after prolonged courses of therapy.\u00a0 Cocci meningitis is a dreaded disease which is practically untreatable.\"Nikkomycin<\/a><\/p>\n

The nikkomycins could fill this gap. Nikkomycins are peptide-nucleoside drugs that act as chitin synthase inhibitors. Despite this new mode of action, impressive fungicidal activity and a good safety record in early clinical trials, they have not attracted much attention or funding.\u00a0 This lack of interest by Big Pharma is clearly related to NikZ\u2019s narrow spectrum which is confined to cocci and blasto.<\/p>\n

A group of researchers\/clinicians with a long track record in this field are now taking matters into their own hands.\u00a0 With the help of the Univ. of Arizona, they formed Valley Fever Solutions, Inc. with the single-minded goal of developing NikZ as an orphan drug for cocci.\u00a0 Of note, on Oct. 7, 2014, NikZ received QIDP status<\/span> and Fast Track designation from FDA.\"ValleyFeverSolutions\"<\/a><\/p>\n

As already mentioned, nikkomycins are chitin synthase inhibitors.\u00a0 Despite the fact that chitin is part of the most fungal cell walls, the activity spectrum is narrow.\u00a0 Here a short summary of the antifungal spectrum based on animal (murine) data:<\/p>\n

    \n
  1. Coccidioidomycosis: This is the primary intended use for nikkomycins. Seminal studies conducted by Richard Hector at Bayer showed that nikkomycins can convert a mortality rate of 100% into a survival rate of 100%.[2]<\/a><\/li>\n
  2. Blastomycosis: Studies by Clemons showed that nikkomycin is more active than itraconazole and probably equipotent (at high doses) to amphotericin B.[3]<\/a><\/li>\n
  3. Histoplasmosis: There seems to be at least partial activity against Histoplasma. In a murine model, nikkomycin prevented mortality and reduced pulmonary fungal CFU\/g in tissue (the latter not as much as treatment with itraconazole or amphotericin).[4]<\/a><\/li>\n
  4. Cryptococcus: There are few studies addressing the activity of nikkomycins against this pathogen.\u00a0 Combination therapy with azoles provided additive \/ synergistic activity.[5]<\/a><\/li>\n
  5. Candida sp.: Although the chitin synthase in Candida is very prone to inhibition by nikkomycin, NikZ has little activity against intact fungal cells.\u00a0\u00a0 Candida are not susceptible to nikkomycin monotherapy but combination therapy with azoles may provide additive \/ synergistic activity 6<\/sup><\/li>\n
  6. Aspergillus sp.: In the mouse model, Nikkomycin monotherapy\u00a0 was ineffective, however, when combined with the candin micafungin survival was significantly improved.[6]<\/a><\/li>\n<\/ol>\n

    In summary, there is good to excellent animal efficacy data for cocci and blasto. Future\u00a0clinical data will clarify the usefulness of NikZ in man and in these and other fungal infections. \u00a0There is great need for better therapies and more treatment options for patients with Valley Fever.\u00a0So far, it looks like NikZ could\u00a0fill this gap.<\/p>\n

    References:<\/strong><\/p>\n

    [1]<\/a> http:\/\/emedicine.medscape.com\/article\/215978-overview
    \n    [2]<\/a> R Hector AAC 34: 587, 1990
    \n    [3]<\/a> K Clemons\u00a0 AAC 41: 2026, 1997
    \n    [4]<\/a>\u00a0J Goldberg.\u00a0 AAC 44:1624 2000
    \n    [5]<\/a>\u00a0R Li.\u00a0 AAC 43:1401, 1999
    \n    [6]<\/a> K Clemons.\u00a0 Med Mycol.\u00a02006 44:69, 2006<\/p>\n","protected":false},"excerpt":{"rendered":"

    Besides azoles, candins and the polyene class of antifungals there is not much to select from when it comes to systemic fungal infections.\u00a0 Until the recent arrival of voriconazole and posaconazole, infections caused by molds always required amphotericin B to control.\u00a0 Only for Candida several good treatments exist on the Continue reading Nikkomycins Are Finally Getting Some Respect<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":1083,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":false,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[19,3],"tags":[471,309,650,225,220,648,651,644,642,649,646,5,647,150,641,622,645,643,604],"class_list":["post-1079","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-qidp_antibiotic","category-the_news","tag-amphotericin-b","tag-antifungal","tag-aspergillus","tag-azole","tag-bayer","tag-blastomycosis","tag-candida","tag-candin","tag-coccidioidomycosis","tag-cryptococcosis","tag-endemic-mycoses","tag-fda","tag-histoplasmosis","tag-itraconazole","tag-nikkomycin","tag-nikz","tag-orphan-drug","tag-valley-fever","tag-valley-fever-solutions"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/10\/cocci-slider.jpg?fit=640%2C200&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-hp","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":5500,"url":"https:\/\/allphasepharma.com\/dir\/2025\/09\/29\/5500\/draft-fda-guidance-for-coccidioidomycosis\/","url_meta":{"origin":1079,"position":0},"title":"Draft 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garnered an indication for invasive aspergillosis. However, it failed where other azole antifungals succeeded: in a pivotal trial, not yet published, the drug was inferior to Caspofungin in the treatment of invasive candidiasis\/candidemia in non-neutropenic patients\u00a0[1]. To provide some background: in\u2026","rel":"","context":"In "QIDP Antibiotics"","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"Crescemba Gamble copy","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/03\/Crescemba-Gamble-copy.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/03\/Crescemba-Gamble-copy.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/03\/Crescemba-Gamble-copy.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":5569,"url":"https:\/\/allphasepharma.com\/dir\/2025\/10\/16\/5569\/the-antifungal-landscape-1\/","url_meta":{"origin":1079,"position":4},"title":"The Antifungal Landscape – 1","author":"Harald","date":"October 16, 2025","format":false,"excerpt":"Some newer azoles are still in development, but most only target candidiasis.\u00a0 Many years ago we saw development of nikkomycin (Nik Z), a drug mainly for coccidioidomycosis (Valley Fever).\u00a0 It has no appreciable activity against candida or aspergillus.\u00a0 Then there is ibrexafungerp, a promising new agent against C. albicans and\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/10\/antigungals-table.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/10\/antigungals-table.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/10\/antigungals-table.jpg?resize=525%2C300&ssl=1 1.5x"},"classes":[]},{"id":344,"url":"https:\/\/allphasepharma.com\/dir\/2014\/06\/19\/344\/the-amazing-sulfonamides\/","url_meta":{"origin":1079,"position":5},"title":"The Amazing Sulfonamides","author":"Harald","date":"June 19, 2014","format":false,"excerpt":"Sulfonamides really cover more infectious territory than most other antibiotics. 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