Wow! We got trolled by a not smart middle schooler

Wow! We got trolled by a not smart middle schooler yesterday! Fun!

I've been catching up on much of the ctix buzz. There is a lot of it. Much excitement. Like many of you, I look at the solid work this company is doing and believe that Kevtrin will prove to be efficacious. So far - things look good. A confidence inducing aspect of this small company's communication is their factual prs. They do not pump. They are obviously an evidenced-based team and present only solid, not speculative, reports. I do see much speculative buzz - not a bad thing - but many posts on another board are claiming the pr stated-without-stating efficacy. Biotech investors can often fall into the trap of reading what they want to see behind the black and white words of their company's prs. This drug may have already shown efficacy. It may not have. Such a claim was not made in their recent pr or in the email from Leo to Kelt.

I have read many posts claiming that the starting dose was large. Not true. Starting dose based on cumulative preclinical results of animal mtd - humans are started at a fraction of that. We are unique and unpredictable creatures. First cohort is a test run. Newer cancer agents with more direct molecular actions are safer to start than the old chemo drugs - but any novel agent first administration is done cautiously. So doubling it for second cohort again does not indicate large dose. Leo reminds us of this when he says to Kelt: "Remember that the dose given is very low as per the clinical protocol, and dosing escalates on every future cohort."

What we know: "the group of subjects has been reported to be within normal parameters of the clinical protocol."  Pharmacodynamic monitoring has shown that the patients have not suffered negative effects in their blood counts, renal function, hepatic function. Specifically mentioned dose limiting toxicity measures in trial protocol were thrombocytopenia, neutropenia, fever.

"we have not seen any of the toxic side effects that are commonly associated with chemotherapy at this point." This drug is being well tolerated so far. Toxicity in this usage refers mostly to negative side effects experienced by the patient, nausea, vomiting, diarrhea, and the negative alterations in hematologic, renal or hepatic profile. That is all we know.

Continuation of treatment to first cohort is commonly allowed if no evidence of toxicity exists. Continuation does not indicate efficacy, just lack of toxicity. Do no harm. Hope alone can extend lifespan. The FDA knows this and thus allows patients to continue treatment beyond their initial cohort phase if the drug is well tolerated. I have read posts indicating some people believe the first cohorts dose will be increased and that is most unlikely. If approved, they will continue to receive their first cohort dose and the next cohort will receive increased dose. That is the way it is usually done in cancer trials. The lack of toxicity indicates that the IRB will approve continuation of therapy for the first cohort. CTIX prespecified a couple of parameters that must be met for cohort continuation in their trial protocol: "

• For patients to be eligible for a new treatment cycle, ANC must be greater than or equal to 1000 cells/mm3 (ANC means absolute neutrophil count)
  


• Platelet count greater than or equal to 100,000/mm3. For patients to be eligible for a new treatment cycle, platelet count must be greater than or equal to 75,000 /mm3

In Kelts query to Leo - Kelt asked "is there anything these latest samples could reveal that earlier samples might not?". Leo didn't really answer - so I will. The routine (pharmacodynamic) monitoring done so far has been testing for toxicity. Really safety testing. Is this drug putting strain on the kidneys? Is this patients platelet count being suppressed (thrombocytopenia)? Is this patient at risk for hemhorrage? These patients have had their safety monitored very closely since the first Kevetrin administration. Now - the pharmacokinetic testing is a bit different than that routine  monitoring that has definitely been taking place since that start of the trial. The batch of 84 samples undergoing pk evaluation will show the drugs action in the body - information about the drugs therapeutic window will begin to emerge. When does Kevetrin reach peak levels in the blood after administration? How long are those peak levels sustained? How is the drug distributed throughout the body?How many times does it go through the liver before the body excretes it? What does the liver do to the drug? How does the body excrete it?Can a multiple dosing regimen be created to keep the drug concentrations high enough,ie, can we mathematically derive a therapeutic dosing window? This early pk testing is exciting. I want to read into it and say something wonderful about possible efficacy but such a thing would not be reality. It is hard not to read too much into the information that has been given to us. This is an exciting drug. Perhaps the most exciting one of our time. But early pharmacokinetic testing does not mean efficacy has been seen yet.

One statement in Leo's letter to Kelt does have me doing a little of that 'read between the lines' thing that got me started on this post to begin with. It is this: " As far as the lab tests for the p21 biomarker, we have not received word on the timing of these tests.  As per the title of the study, p21 (biomarker for p53) is a secondary goal.  We dont know when they will do such."  He says they have not received word on the timing of those tests. Now that is truly careful wording on his part...Those tests could be done already. He didn't say "we do not know when that testing will begin". Just...no word on the timing...Hmmm...