Novogen - Dosages and comments

Check out the following. Look closely at the comments where Novogen say Phenoxodiol is required at levels no less than 5ug/ml to work.

The stage one trials used Phenoxodiol at levels less than 5ug/ml and therefore shouldn't have worked at all and yet they saw the anti cancer effect even in the least intensive treatment (weekly injection as the drug was only in the body for around 2 hours a week).

Now looking forward, Phase II trials will ramp the dose up to well above the 5ug/ml and probably continuously. Surely we should see a much more potent anti-cancer affect. Now add the duel drug which increases death receptors and the anti-cancer effect should be even greater.

Comments by Novogen:

The key objective of Phase 1 trials is to determine how safe the drug is and what side-effects might be expected. Given that sphingosine kinase is such a critically important protein in all cells, both normal and cancer, this obviously is of vital interest to us.

But we have a second important objective, and that is to determine how best to use the drug. We know that in order to work, phenoxodiol probably needs to be present in blood at levels no less than about 5 ug/ml. We would assume that the longer we can hold this blood level, then the better the drug will work, but we do not know the minimum time that we need to hold it. The drug has a short half-life (45 minutes) meaning that a single dose (either a single intravenous injection or a single oral dose) would only give meaningful blood levels for about 2 hours.

We are developing both an intravenous form and an oral tablet form of phenoxodiol. The intravenous form is being developed as means of delivering high blood levels to patients with advanced cancers in order to achieve maximum effect. The oral form would be used for long-term maintenance therapy.

Trials #1, 2 and 3 are using the intravenous dose form. The reason for doing three trials is that we need to build up the intensity of our treatment regime carefully until we confirm that the drug is safe.

Trial #1 (Sydney) is almost complete. The early data was presented recently to a cancer conference in Miami and released via the ASX and Nasdaq. This trial used the least intensive treatment regime of a single intravenous injection once weekly. That is, these patients had meaningful blood levels (> 5 ug/ml) of phenoxodiol for only 2 hours each week. Because of such a short period of effective blood levels, we regarded this as a regime that would be highly unlikely to yield any anti-cancer response.

Not unexpectedly the drug has proven to be well tolerated, the only toxicities being mild and temporary. But quite unexpectedly, the drug also showed an anti-cancer effect, stopping growth of aggressive tumours in 3/17 patients. Given the relatively low intensity of this treatment regime, this is a highly encouraging outcome.

Trial #2 (Sydney) involves giving the drug by continuous intravenous infusion over 7 days followed by 7 days of rest, and then repeating that at least twice. Despite these patients receiving on a weekly basis up to 50x the amount of drug that patients in the first study received, the levels of phenoxodiol in the blood of these patients are still below 5 ug/ml and will not achieve that level until the last 3 patients are started. The number of patients already with stabilisation of tumours has not yet been publicly announced.

Trial #3 (Cleveland, USA) involves the same regime as Trial #2 but rises ultimately to a much higher dose. We currently have 10 patients on this study, with the number already showing stabilisation of aggressively growing tumours not yet publicly announced. It is this trial that has received expedition from the FDA to now allow higher doses to be administered to cancer patients sooner than would have been the case under the previous protocol.

The patients in Trials #1-3 have advanced cancers across a broad range, excluding leukaemias. The tumours that have responded to phenoxodiol in these trials represent many types including melanoma, pancreatic cancer, renal cancer, adenocarcinoma, and prostate carcinoma.