Well the best DEP news SPL has ever had probably. The TRAEs...

Well the best DEP news SPL has ever had probably. The TRAEs (Treatment Related Adverse Events) are no surprise to me - but they lead to the possibility of higher doses for patients which may improve PFS (Progression Free Survival) and OS (overall survival). Looking into that was not the purpose of this trial.

For Prostate cancer related mCRC, the 2022 Esmo results were 3.9m PFS, vs these results at 4.4m.It may be with more time we would get a slightly higher result again.
PSA about the same - no surprise.
TRAE's - the same at 16%.

So there seems to be some news to come. The DEP Docetaxyl and Covid trials obviously. But also the status of applying for early marketing approval to avoid a phase 3 trial, based on 505(b)(2) - see below. Looks like reasonable odds of success to me, but I am biased as an SPL holder. I still think the market is unaware of this pathway, and expects a phase 3 trial is required, when there appear good odds of far earlier marketing approval.


505b2 Guidance for industry: https://www.fda.gov/media/72419/download


Four categories of acceptable changes:


· Dosage form. An application for a change of dosage form, such as a change from a solid oral dosage form to a transdermal patch, that relies to some extent upon the Agency's finding of safety and/or effectiveness for an approved drug. (My comment - fortunately we aren't going anywhere near as far as that example, which has qualified)

· Strength. An application for a change to a lower or higher strength.

· Route of administration. An application for a change in the route of administration, such as a change from an intravenous to intrathecal route.

· Substitution of an active ingredient in a combination product. An application for a change in one of the active ingredients of an approved combination product for another active ingredient that has or has not been previously approved.


Examples of what may be acceptable:


· Formulation. An application for a proposed drug product that contains a different quality or quantity of an excipient(s) than the listed drug where the studies required for approval are beyond those considered limited confirmatory studies appropriate to a 505(j) application.

· Dosing regimen. An application for a new dosing regimen, such as a change from twice daily to once daily.

· Active ingredient. An application for a change in an active ingredient such as a different salt, ester, complex, chelate, clathrate, racemate, or enantiomer of an active ingredient in a listed drug containing the same active moiety.

· New molecular entity. In some cases a new molecular entity may have been studied by parties other than the applicant and published information may be pertinent to the new application. This is particularly likely if the NME is the prodrug of an approved drug or the active metabolite of an approved drug. In some cases, data on a drug with similar pharmacologic effects could be considered critical to approval.(comment - for Irinotecan)

· Combination product. An application for a new combination product in which the active ingredients have been previously approved individually.

· Indication. An application for a not previously approved indication for a listed drug.

· Rx/OTC switch. An application to change a prescription (Rx) indication to an over-the-counter (OTC) indication.

· OTC monograph. An application for a drug product that differs from a product described in an OTC monograph (21 CFR 330.11), such as a nonmonograph indication or a new dosage form.

· Naturally derived or recombinant active ingredient. An application for a drug product containing an active ingredient(s) derived from animal or botanical sources or recombinant technology where clinical investigations are necessary to show that the active ingredient is the same as an active ingredient in a listed drug.


Not acceptable:


· An application that is a duplicate of a listed drug and eligible for approval under section 505(j) (see 21 CFR 314.101(d)(9)); or,

· An application in which the only difference from the reference listed drug is that the extent to which the active ingredient(s) is absorbed or otherwise made available to the site of action is less than the listed drug (21 CFR 314.54(b)(1)); or,

· An application in which the only difference from the reference listed drug is that the rate at which its active ingredient(s) is absorbed or otherwise made available to the site of action is unintentionally less than that of the listed drug (21 CFR 314.54(b)(2)).