Replies to post #948 on Biotech Values

[mr sunshine]

Dew; what is your take on the Pars presentation? $10,000,000 expected this year from B. and L.;Cardiac surgery, etc. ; 3 or 4 expected announcements this year. Enroll end soon; unblinding before year end; ( I assume some traders were expecting some big surprize announcement; and sold today.)

[mid_swe]

Dew, I will carefully follow QTc-prolongation in the comming abstracts, but I feel you are only looking at the worst case senario. "One of these patients had pre-existing "significant cardiac risk factors and underlying, asymtomatic, severe coronary artery disease."

From a Oxigene PR in 2002.

"One patient with anaplastic thyroid cancer had a complete response and is alive 30 months after the treatment," the article states. Two other patients, one with metastatic colon cancer and the other with metastatic thyroid cancer, experienced prolonged (more than one year) freedom from disease progression.

Dr. Remick and his team found no significant myelotoxicity, stomatitis or alopecia. Researchers noted four episodes of dose-limiting toxicity, including two episodes of acute coronary syndrome. One of these patients had pre-existing "significant cardiac risk factors and underlying, asymtomatic, severe coronary artery disease." In the other patient, EKG changes normalized and there was no elevation of any serum marker indicative of cardiac damage. No cardiac events were observed in the two other completed Phase I studies.

"The drug appears to have demonstrable clinical activity early in its clinical development," the article reports. "Important clinical observations with CA4P include: a lack of traditional cytotoxic effects." The authors conclude that combining this compound with other modalities including cytotoxic drugs, radiation and antiangiogenesis agents will likely be an attractive prospect.

For AMD I pass my comments until I see some trial results.

[rph_in_wi]

Re: local formulations of CA4P.

I agree with Dew that these questions are definitely important factors for the long-term use of CA4P.

Localized formulations of ophthalmic medications are not always the answer to eliminating cardiac effects. There are a number of currently available ophthalmics that are absorbed into the systemic circulation and cause significant clinical effects, even at low doses. An example would be Timoptic, a betablocker used for glaucoma, that can cause significant slowing of the heart rate.

Also, in the past 10 years, I have seen numerous medications get pulled off the market due to a newly found cardiac side effect. The fact that they have an idea about some QT elongation should cause the FDA to, in the least, force more study of these effects. IMO, this could delay/hold any approval.

RPH

[DewDiligence]

Second addendum on CA4P’s QTc-prolongation:

On the OXGN board on Yahoo (#30626) “jeffreyvs/ azpharmacygirl” has cited a reference from Bayer on QTc-prolongation:

http://tinyurl.com/3dlul

According to the guildines in the above reference:

“Any prolongation of less than 30 milliseconds seems to be of no concern about a potential risk. Prolongation of more than 60 milliseconds raises a clear concern.”

By implication, QTc-prolongation between 30ms and 60ms inclusive is a cause for some concern.

In trying to make a case that CA4P’s QTc-prolongation is not worrisome, “jeffryvs” from the Yahoo board ends up making a strong argument for the opposite conclusion.

At 4 hours after treatment, the mean QTc-prolongation of patients in the CA4P trial was 30.8ms (see bottom of iHub message #908: #msg-2178433), which is within the middle range (30-60ms) that indicates possible trouble. Moreover, this 30.8ms figure was an average figure for the patients in the CA4P trial and hence the QTC-prolongation values of some patients in the trial must have been greater than this average.

One must conclude that a significant proportion of CA4P patients in the trial in question had QTc-prolongation values that would at least warrant extra caution and a high level of continuing scrutiny.