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Biotech / Medical : PARANOID! TIRED OF TALKING TO YOURSELF? LET'S TALK(TTP) -- Ignore unavailable to you. Want to Upgrade?

To: NeuroInvestment who wrote (264)	1/21/1999 12:02:00 AM
From: John Metcalf	Read Replies (2) \| Respond to of 626

"no real news has emerged other than Novartis reaffirming what was already in print--and enlarging the total Phase III target from 2600 to 3300" That was big news to me. First, Novartis is spending big money, therefore sees big value. Second, only 600 of these trial participants will be in the US (18%). This means that Novartis sees value beyond lessening of the agranulocytosis side effect of their Clozaril. In the US, weekly blood levels are required for Clozaril users, and this accounts for more than half the annual cost of use. In Europe, the standard of care is to reduce lab work if no problems are encountered in the first few months. If Novartis had weighted the trials heavily towards the US, I would have concluded that they were aiming at a Clozaril replacement with lower monitoring costs. However, the ZEUS trial is slanted 82% towards the rest of the world, so I suspect Novartis is anticipating other advantages.

To: NeuroInvestment who wrote (264)	1/21/1999 1:55:00 AM
From: Miljenko Zuanic	Respond to of 626

Hi NI: Welcome and hope You will continue to contribute on this and other SI thread. Even if I have to leave and do not post further. Nonetheless, it is more likely that we will continue to see things differently. << MZ and I have a long history of not seeing things similarly, so here is another one.>> OK, than I will tried to clarify myself or defend, whatever one chose. << My information from CFO was that the Pivanex trial in squamous cell lung cancer is 36 pts, and if positive--to be known sometime in 2Q99, it could then be expanded into a pivotal PhII/III.>> Pivanex did show hint of efficiency in their PI/II trial, so this trial is to confirm or denied drug benefit. I wrote in my last post: “By now their PII trials should be at half of the first PII phase. “ first PII phase not first PII trial, so I mentioned by this two or more PII phases for this PII trial. Based on their news release about this trial (July 98). This type of protocol where first pts group is analyzed for efficiency/safety parameters and according to trial end-point is normal for almost all first indication PII trial (or PIIa which can be expanded to PIIb/III). There are no need to put additional cancer patients at risk if drug do not have initial positive results (I thing that ~5-10% of pts , depend on indication, must have clinical positive respond). Nonetheless, butyric acid anticancer property are known for some time and it is not new. However, butyric acid (as free drug) is to toxic at therapeutic dose and it is trick and research desire to chemically modify compounds in to less toxic drug (pro-drug) and at the some time with significantly improved pharmakokinetic property. If You are not familiar with pivalyloxymethyl ester modification for acids or alcohols and this pro-drug advantage, learn about. I am not saying that Pivanex will work, but I do have strong filing that it is worth a shoot. TTP will not go bankrupt after conducing trial for 36 pts. I guess You did read HMR Iloperidone package (from preclinical studies to PII trials results). For sure nothing is granted in drug development process, not even positive PIII trials (IPIC or ERGO). So, regardless the PII iloperidon data (from two doses) the better approach will be to value drug based on up to date results, whole development process, and Novartis intention. John nicely explain and argue about Novartis commitment to this drug. I have few more thing to add. Based on TTP Aug.98 news, where Novartis guy confirmed start of Ilo clinical programs (PIII trial with Ilo two dose and Holoperidol as control arm), I will assume that this trial is repeated PII protocol and with HMR Ilo pills. It means that drug is for hospital setting and certain enrollment conditions and/or acute schizo-pts conditions. As You know, Novartis has full control and manufacturing right to this compound. HMR pills supply (two dose) wasn't (from CFO) sufficient for large multiple PIII. So, Novartis needed to manufacture itself drug clinical quantity (three independed batches), bulk drug and pills. Validate process, run pills stability and some short animal studies (specially if they chose to reformulate drugs which I will not be surprised based on their experience with CNS drugs). All this postponed start of the pivotal PIII clinical trials programs. Many of my on-line friends know that I never lost confidence on Iloperidone or Novartis comitment. << I am not devaluing iloperidone's potential, just noting that no real news has emerged other than Novartis reaffirming what was already in print--and enlarging the total Phase III target from 2600 to 3300.>> Second news on PIII trials was not repeated of the Aug. news. Trial is for different setting, different protocol, three doses, different pts population, .... IMO. Why will Novartis initiate two times some trials? In Aug. Novartis started clinical program for Iloperidone with the first PIII trial in US for chronic schizo (actually this may be test trial) and now is expanding with additional PIII trials. From NAMI (9-1998): “New drug in development” nami.org <<Iloperidone Iloperidone, a mixed D2/5HT2 antagonist with preferential affinity for FHT2A receptors in humans, has shown good activity against both positive and negative symptoms of schizophrenia and very low EPS liability. A trial is being conducted to evaluate the safety of two titration schedules and to evaluate the effect of iloperidone on cognitive functions. The target population includes chronic schizophrenic patients who are not adequately benefiting from their current antipsychotic treatment. Later in the year at approximately 180 sites in 21 countries, larger clinical trials will be conducted to evaluate the drug's effect on different aspects and symptoms of schizophrenia including: depressive symptoms, cognitive functioning, and reduced incidence of extrapyramidal symptoms. Novartis Pharmaceuticals Corporation is currently conducting Phase III trials. >> So who is wrong and who correct? Is this news for initial PIII trial, or news on additional PIII with Ilo clinical development plan? And, this new PIII trials are with much higher importance than first one, started in Aug. If I am confused here, my apologize to readers for misunderstanding the current Ilo clinical status. However, I will not jump like YOU and indicate that this was news without event. It is significant news for TTP, but many didn't get it yet. Miljenko PS: Lelim, Novartis is not company which will disclose what are their real intention. So, this little news is going long way. Specially after Abbott, Pfizer and Lilly (label expansion) failed.

To: NeuroInvestment who wrote (264)	1/21/1999 1:47:00 PM
From: scaram(o)uche	Respond to of 626

Dr. Tracy: Thanks for the numbers re. piv phase II. Big difference, and important. We get a lot of key stuff from you. Don't know what to say about (1) your first sentence, and (2) your interpretation of the delay for the phase III. First, I value and use the opinions and information posted/shared by both you and MZ. I have made nice profits, repeatedly, by following Miljenko's research. It doesn't make much sense, IMO, for anyone to point at inconsistencies, when the effort to openly share research is so apparent. The delay in trial launch.... I took the Novartis steps to control manufacturing as a positive (of course, I was out of the stock during the period of confusion, so it's easy for me to have that attitude). >> and enlarging the total Phase III target from 2600 to 3300 << A very expensive commitment to the development of ilo. I'm glad to see that you are on piv in addition to ilo, and enthusiastically look forward to your further insights. Rick