So I'm sure several people so the article put out today by the Street. Any thoughts? My understanding concerning the data he put forward was that when Endocyte did their trials, they initiated them with a specific intent. Most of the things he mentioned I don't feel were in line with the intent of the trial. Is there another drug out there that can treat platinum resistant ovarian cancer? I don't think there is. I do have to agree with him to some extent that Europe may wait to see the results of phase III. I'm interested in what everyone's thoughts or perspective.
Folks, this piece is so full of distortions. Let's look at at the claims the article makes a bit more closely.
1. "In fact, the entire vintafolide benefit Endocyte observed in the phase II Precedent study is readily explained by the fact that vintafolide-treated patients in this unblinded study received significantly more PLD than the control patients (162.5mg vs. 100mg.) The baseline characteristics of the control patients were also better than patients in the vintafolide arm."
Two things wrong here.
- Both arms received 50 mg PLD.
- "The baseline characteristics of the control patients were also better than patients in the vintafolide arm". Exactly. That would make the control patients healthier, so that would work in ECYT's favour, not as is implied against them. In fact when this difference is taken into account there is a strong OS benefit.
2. "What appears to be "futility" of vintafolide monotherapy in the lung cancer study -- even though that term was not used by independent monitors -- raises significant concerns about the drug's anti-cancer activity and portends equally negative results from the vintafolide-docetaxel combination therapy arm."
The review board did not ask to stop the single arm vintafolide trial which means that vintafolide is likely to have the same effect as Doxil, which is what preclinial studies also showed. No surprises there. That's way off from being futile. If two drugs with equal effect are combined, it is likely that there will be improvement. Preclinical data also shows just that.
3. "The vinca alkaloid class of drugs -- of which vinblastine is a member -- have been shown in much larger clinical trials to be equivalent to taxanes. Krazkowsi et al compared vinflunine (another vina alkaloid) to docetaxel in 551 second-line lung cancer patients. Docetaxel dosing and schedule was the same as used in the Endocyte study. The result: No difference in response rate, PFS or overall survival between vinflunine and docetaxel."
Here the vinca alkaloid class is shown to be as effective as doxil. Not bad. Combine the two and you'll likely see improvements. The trial after all is comparing Doxil + Vintafolide against Doxil alone. So get your comparisons straight. But it gets worse.
4. "Why is this bad for Endocyte? Because the vinflunine dose in the Krazkowski study was significantly higher than the vintafolide dose by Endocyte in its lung cancer study. Total vintafolide exposure for the first three weeks of dosing is 10mg, or more than 30-fold (on a mg-to-mg basis) lower than total vinflunine exposure. When looking at the molecular weight of each drug, the vinflunine dose was 60 times higher than vintafolide."
Oh boy. Vinflunine is a much less potent drug than vinblastine which is what Vintafolide is based on. We are talking about two orders of magnitude. Please read the article "Antimitotic and tubulin-interacting properties of vinflunine, a novel fluorinated Vinca alkaloid" where the two are compared.
Sentiment: Strong Buy
I am extremely optimistic about the likelihood of EU approval. I am a physician and I read the PRECEDENT study carefully. They met their primary endpoint, which is progression free survival. Although overall survival was not met, this was a secondary endpoint. Furthermore, there was a trend toward statistical significance in people with high folate receptor activity (and I suspect that if there were more patients enrolled with high folate receptor activity, an improvement in overall survival in that subset of patients would be statistically significant). If for some chance there is a delay in EU approval, I have no doubt that this mechanism of action is very promising and will inevitably do well in the long run.
Sentiment: Strong Buy
I am also a physician. I concur with your opinion. PFS is extremely important and if Endocyte can duplicate the PFS shown previously, then the chances of EU approval are very good. Anyone with cancer can attest to the significance of PFS in terms of morbidity and quality of life. The company is certainly part of the movement towards personalized medicine.
Thank you for that post and the encouragement. I feel this company has a promising approach to treating cancer. I failed to post this in my original post but in the last conference concerning the nsclc trial that 80% of the folks decided to stay on it. I felt that was huge and rather contradicts what that article states. I have high hopes for this company. I just hope they don't get dashed, haha.