Now here’s an embarrassing admission for a drug development company to have to make …
According to a media release issued earlier today by Nymox Corp., the company is unable to accurately determine the efficacy of a randomized, 142-patient, Phase II study (NX03-0040) of its investigational drug NX-1207 in the treatment of prostate cancer.
The primary efficacy endpoint, the percentage of subjects with undetectable prostate cancer (negative biopsy) 45 days post-treatment in the region of the prostate where the baseline cancer was detected, proved to be unable to be assessed because of the high percentage of false negative repeat biopsies in the active surveillance control arm.
How do they know that these negative biopsies were “false negative”? Maybe there was just a high occurrence of spontaneous remissions!
As many of our regular readers will be well aware, the ability to accurately re-biopsy small areas of tumor in a specific portion of the prostate is low — unless such biopsies are all done under sophisticated multiparametric MRI/TRUS fusion guidance (and it can be hard even then). Because this was a three-arm trial (46 men in an NX-1207 high-dose arm; 47 in an NX-1207 low-dose arm; and 48 in a control arm), there was always going to be little leeway for difficulties in being able to accurately re-biopsy the men in any arm of the trial.
The company goes to great pains to point out a series of positive results from the trial, as follows:
- There was an overall benefit in terms of reduced progression in patients with low-grade, localized prostate cancer (clinical stage T1c) treated with a single injection of NX-1207 into the area of the prostate where cancer was found.
- There were no significant safety issues or side effects associated with treatment with NX-1207 (and this is consistent with earlier clinical trial experience).
- Patients who received a single targeted injection of NX-1207 had less evidence of cancer progression in the treated area than untreated patients (0.9 vs 6.3 percent; relative risk = 0.15) as determined by Gleason grade.
- Overall, the number of biopsy cores showing higher grade of malignancy was significantly lower among the patients treated with NX-1207 than among the control patients
- In the treated area of the prostate (p = 0.032)
- In the treated lobe of the prostate (p = 0.004), and
- In the prostate overall (p = 0.004).
- The total volume of more malignant cancer detected in the treated area and throughout the prostate was apparently statistically significantly reduced in the NX-1207 treated patients compared to the controls.
- PSA levels decreased more from baseline in drug-treated patients receiving a high dose of NX-1207 (15 mg) compared to those receiving a low dose (2.5 mg), and the PSA levels in the controls were unchanged.
- In the small subgroup of patients with an increased Gleason grade on repeat biopsy, the mean PSA in NX-1207 treated patients also decreased as compared to controls (in whom the PSA levels were unchanged).
But the bottom line is that Nymox is unable to tell whether there was a statistically significant impact on the primary endpoint for the study.
Apparently,
… an unexpectedly high proportion of enrolled patients had baseline biopsies with only evidence of an extremely small tumor (5 percent or less of their single positive core biopsy). This included 68.8 percent of the active surveillance control patients. For 85 percent of these control patients, the second biopsy was unable to detect the known cancer tumor found by the original baseline biopsy, making meaningful analysis of the percentage of subjects with a negative second biopsy impossible.
The company’s management is apparently fully committed to moving forward with the development of NX-1207 for the treatment of low-risk prostate cancer. However, any Phase III trial will need to be conducted with a great deal more focus on the ability to re-identify cancer in any men in a control arm.
The Nymox CEO is quoted as stating that,
We emphasize that these results are based on a single focal injection of drug, which is a minimal treatment. A multiple injection regimen is expected to further increase efficacy.
The “New” Prostate Cancer InfoLink is of the opinion that Nymox would be wise to clearly demonstrate efficacy with a single, focal injection of NX-1207 before exploring the potential value of multiple injections.
Filed under: Diagnosis, Living with Prostate Cancer, Management, Risk, Treatment | Tagged: endpoint, NX-1207, outcome, Phase II, trial |
THE "NEW" PROSTATE CANCER INFOLINK 
This is a very odd company, and I sort of wonder about the validity of anything they are doing. Years ago I had a very enlarged prostate. (It has been surgically reduced now.) Nymox was touting this very same drug as an almost miraculous treatment for BPH. Supposedly, one injection would radically shrink the prostate and last for many years. (It was supposed to be much more effective than the two drugs used for this purpose … with no side effects.) I had tried one of the drugs, and couldn’t tolerate the side effects, so I was looking forward to this coming to market. The thing is, it never came to market. Suddenly, they were testing the drug for effectiveness against low level prostate cancer and I can find nothing more about its supposed original purpose. The company is publicly traded … so, color me skeptical.
Doug:
The Phase III BPH trial is ongoing. Indeed, the final results of this trial must be imminent.
However, I tend to agree with you that (at least to date) the evidence for the value of NX-1207 in treatment of anything is not exactly compelling (yet).
Does anyone know what NX-1207 is? Is it an anti-inflammatory?
Doug
Doug:
Nymox’s CEO has been quoted as having stated that NX-1207 is a “proprietary protein that leads to apoptosis [cell death].” That seems to be as much as anyone at Nymox has ever been willing to say about the product and/or its mechanism of action.
If it were “proprietary”, they could file for a patent and make the info public.
Doug:
One of the key “tricks” to developing profitable biopharmaceuticals is to delay one’s patent application for as long as one can. Why? Because the longer you can delay filing the patent, the longer you have before anyone else can discover or elucidate exactly what it is your product is and does (so as to be able to develop a direct competitor) and, even more importantly, the greater the time you have to make money from the product if it is approved for marketing. It is of course perfectly possible that a patent was filed on NX-1207 years ago, but that it was done in a manner that has made it extremely difficult to identify that patent. It would actually be very unusual to get into Phase III trials with a non-patented product.
Thanks for the explanation.
If the product actually works, and they had opened it up to the research community, we would know whether it works or not.
We need a better system to test and get these drugs out more quickly.
I was injected with NX-1207 for BPH. Several months into the trial, my PSA spiked. The urologist heading the trial pushed for immediate biopsy and then pushed for a radical prostatectomy, right away. When I asked about other treatments, he got agitated and barked, “Why would you want to keep that tissue!” I left the trial that day. I later found out that the cancer was low grade and that I could adopt a watchful waiting attitude.
AJ:
You are not the first person that I have heard/read about that was “strong-armed” by the urologist/support team. I realize this was a while back, but would be curious to hear a little more information on your experience if possible … not expecting a response given its been 2+ years since you last commented and this article was posted but worth a shot
Thanks