Separating fact from fiction: US regulatory timelines

One of the goals of the CLINUVEL News & Facts website is to help ensure accurate information is published on the Company. Select pieces on the CLINUVEL News & Facts website – including this one – have been written to address an imbalance of information online. To learn more about the site, click here.

CLINUVEL’s drug SCENESSE® (afamelanotide) was approved by the US Food and Drug Administration (FDA) on 08 October 2019 for adult patients with erythropoietic protoporphyria (EPP). In June 2019 it was announced that the FDA had requested an extension of the Prescription Drug User Fee Act (PDUFA) date, which was ultimately set on 08 October 2019, when approval was granted. Dr Wolgen provided some more context on this moment in his 2019 Annual Report letter:

On 31 May, the FDA used its discretionary tool to request a three month extension to the formal review user fee goal date, providing a new target date 6 October.* We assessed the delay as a positive measure, since the Agency had had ample opportunity to reject the submission, issue a Refusal to File or even request a withdrawal. None of the events had occurred during our submission or review, and our teams kept working towards satisfying all outstanding questions from the agency. It was a period whereby many around us were tested, but the overwhelming majority of investors kept having faith in our teams. A key ingredient to CLINUVEL’s success continues to be our consistency.

* The FDA later clarified the target date as 08 October 2019, see below.

A brief history of announcements on US regulatory interactions and US clinical trials for EPP to date is provided below.

Date Announcement
29 Jul 2008 FDA grants CLINUVEL orphan-drug designation
23 Dec 2008 CLINUVEL lodges IND in US
29 Jan 2009 FDA allows IND status for CLINUVEL’s afamelanotide
30 Mar 2010 FDA allows US clinical trials of afamelanotide in EPP
Breakthrough Australian drug to commence US patient trials (media release)
09 Nov 2010 FDA provides positive guidance on CLINUVEL’s EPP program
09 Feb 2011 CLINUVEL completes first Phase II US study
03 Nov 2011 CLINUVEL demonstrates positive treatment effect of afamelanotide in US Phase II study
15 Mar 2012 CLINUVEL, FDA agree in principle to Phase III study with SCENESSE® (afamelanotide)
22 May 2012 CLINUVEL commences US Phase III trial of SCENESSE® in rare light and UV disorder
11 Nov 2013 Clinical significance and benefit from SCENESSE® in US Phase III EPP study
27 Aug 2015 FDA grants CLINUVEL a Type C Meeting
05 Oct 2015 CLINUVEL and FDA discuss EPP indication and regulatory pathways for SCENESSE®
06 Jul 2016 FDA awards SCENESSE® Fast Track designation for treatment of EPP
18 Jul 2016 FDA accepts SCENESSE® clinical data package for NDA submission
13 Oct 2016 FDA, CLINUVEL to discuss SCENESSE® at pre-NDA meeting (media release)
24 Oct 2016 FDA erythropoietic protoporphyria (EPP) scientific workshop
09 Nov 2016 CLINUVEL agrees with FDA on New Drug Application timelines
19 Sep 2017 CLINUVEL provides update on SCENESSE® FDA filing
14 May 2018 CLINUVEL regulatory update
25 Jun 2018 CLINUVEL completes SCENESSE® FDA filing
05 Sep 2018 US FDA update
10 Jan 2019 US FDA sets PDUFA date for SCENESSE®
03 Jun 2019 US FDA review for SCENESSE® extended by three months (media release)
02 Oct 2019 FDA clarifies SCENESSE® PDUFA date
09 Oct 2019 FDA grants Marketing Approval for SCENESSE®
16 Apr 2020 First US patients to be treated with SCENESSE®


    • Me as a patient Im eagerly looking forward to that one for sure.
      If possible, give us an update on timelines please.

  1. According to your above referenced regulatory filing published to the ASX, Clinuvel submitted its New Drug Application to the FDA for validation on or about June 25th, 2018.

    However, FDA records reflect that they received the NDA and commenced the 60 day validation period on November 8th, 2018.

    Can you explain the discrepancy between these dates?

    • John,
      Have a look at the announcement on 05 September 2018, outlining the FDA request for further information.
      – CUV team

      • Thank you for your response. However, the wording in the 05 September 2019 announcement is the source of my confusion.

        In your 10 January 2019 announcement informing the public of the PDUFA date for Scenesse, you state that the application was filed under 21 CFR 314.101(a), which is the only regulatory pathway available in the US to file a New Drug Application.

        The language in 21 CFR 314.101(a)(1) and 21 CFR 314.101(a)(2) is very precise:
        “”(1) Within 60 days after FDA receives an NDA, the Agency will determine whether the NDA may be filed. The filing of an NDA means that FDA has made a threshold determination that the NDA is sufficiently complete to permit a substantive review.

        (2) If FDA finds that none of the reasons in paragraphs (d) and (e) of this section for refusing to file the NDA apply, the Agency will file the NDA and notify the applicant in writing.””

        The law is very specific in that the FDA MUST file a New Drug Application within 60 days of receipt unless they find one of the deficiencies enumerated in sections (d) and (e). There is no allowance for “requesting further information”. The application MUST be filed within 60 days unless it is found to be deficient.

        We agree that the application was not filed within 60 days of 25 June 2018, and in fact was filed almost 7 months later, with and official FDA submission date of November 8th, 2018.

        From a regulatory standpoint, there are only 3 things that could have possibly occurred:
        (1). The FDA issued a Refusal to File (RTF) letter to the June 25th submission, and Clinuvel corrected the identified deficiencies in a subsequent resubmission on November 8th.
        (2). Clinuvel voluntarily withdrew its June 25th NDA submission sometime before the end of the 60 day validation period, and later resubmitted the NDA on November 8th.
        (3). Clinuvel did not in fact submit the final module of the NDA on June 25th, and instead submitted it on November 8th.

        Based upon the information Clinuvel has released to the market over the relevant period, these are the only 3 scenarios the law allows for.

        The statement that the “FDA requested further information” does not adequately explain what occurred. For example, if Clinuvel had received a Complete Response Letter instead of marketing approval, Clinuvel could technically claim that they received a “request for further information” in the letter, but that does not adequately explain what regulatory action occurred.

        We are in agreement that the FDA did request further information from Clinuvel during the filing period, however, my question is very specific: what regulatory action occurred that resulted in the NDA not being filed until almost 7 months after it was initially submitted?

        Thank you for your consideration.

        • John,

          The Company does not agree with all the statements in your comment and does not verify their accuracy. The suggestion that an RTF was issued is incorrect and has been clearly addressed. The specific regulatory action was a request for additional information, as disclosed. As our final response on this matter, the NDA was submitted under rolling review in June 2018 (the product received Fast Track designation to facilitate this process). Following a request from the FDA, as outlined in the September update, further data were submitted and the FDA validated the dossier in January 2019.

          – CUV team

  2. So… are you guys going to actually answer questions, or are you just going to hide the ones you don’t like?

    • Dear JB,
      CLINUVEL has been evaluating potential further clinical uses of afamelanotide based on scientific evidence and where the greatest impact can be made. At this stage, we are not further investigating the use of SCENESSE® to treat polymorphous light eruption. The Company does not publish information on the number of patients treated in any country. For a review of the distribution of SCENESSE® in the United States, please see our recently published annual report, here.

  3. Dear Clinuvel,

    thanks for the clarification and all of your effort to help patients with rare diseases!



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