My ears were burning (one of the unmentioned side effects of Adcentris BTW).
Yes my sons (and daughters) I'm still with you but in stealth mode. Posting on this board (ANY equity) is tantamount to the wall and head banging act.
So please be assured I'm watching this board and (in) SGEN. After all, $10 isn't that far away on the down.
(LOL. I thought you'd get a kick out of that).
XO and carry on.
I believe you meant that the bar of acceptance can be lowered which was surely the case of Provenge. If memory serves, phase 3 results were: No anti-tumor activity observed. 20% of patients lived an average 8weeks longer. The reason was unknown. It still manages to sell half a billion per year. PGNX has already proven better efficacy. I was surprised FDA set it that low. To me this is still an unmet need and PGNX is a buy.
I'm a bit hesitant with the PSMA-ADC as PSMA had never been a good target for earlier PC antibodies. I believe it is also not very strictly localized to PC cells, but my knowledge is very much incomplete. At one point, I read much about PSMA bec of the SGEN ADC, but have not followed developments. I know PGNX earlier clinical trial reports were not very convincing. Good luck with that anyway. If they report great results, that's when I'll buy in.
Thanks a lot for your insights in this. It helps me a lot in making my investment decision. I bought PGNX a while ago around $5 a share. I am looking forward to a great ASCO report in late January.
Based on the observations following treatment of the patients in the chemotherapy experienced cohort, Progenics has initiated treatment of a cohort of chemotherapy naive patients who have progressed on hormonal therapies. This cohort is now enrolling. Progenics expects that an additional 35 patients will be included in this chemotherapy naive group.
Many thanks to you!
I have not been following the Progenics ADC drug very closely at all.
However, based on the reports you cited it does appear that their drug is associated with a notable and varying degree of suppression of neutrophil production. I suspect that this could possibly be due to cleavage of the toxin from the antibody and release into the systemic circulation and then into the bone marrow to exert its adverse effect on neutrophil production. Other possible mechanisms exist. As the very serious and life threatening effect was seen, in the two patients cited, very early ( within two weeks ) after initiation of treatment, subsequent dosage adjustment downward was not apparently an option. As these were chemotherapy experienced patients, it is unclear as to what degree of related myelosuppression was present in each individual at baseline, before treatment, and if this may have been a ( or the ) critical factor in the severity and poor outcome. As the trial is now being expanded into a cohort of chemo naive patients, it will be informative to observe the frequency and severity of this particular adverse effect in that group in comparison.
Ultimately, the degree of benefit of a drug prospect will have to be weighed against the risks. With very serious or life threatening disorders ( such as metastatic cancer ) the bar of acceptance can be naturally and liberally raised a bit. Also patient selection and timing of initiation of therapy ( e.g. time post chemo to allow fuller bone marrow recovery....as an example ) as well as consideration of initiating treatment at lower doses could become possible treatment strategies to maximize the benefit / risks ratio.
Looking forward to seeing the ASCO report. Hopefully, that will show a quite notable and very encouraging benefit.
I agree that tumor marker and genetic testing to predict response to different therapeutic options is in the upcoming vanguard of clinical practice. However, I do not presently follow this company nor have any opinion presently.
While not directed to me, febrile neutropenia is a common complication for most oncology patients. Since Progenics proceeded with Ph 2 trial for this ADC, as well as a recent extension to that Ph 2 study, with results expected to be released pretty shortly, I doubt that they were too concerned with the safety profile of their ADC.
Our PSMA Development Company LLC subsidiary has a collaboration agreement with Seattle Genetics, Inc. under which SGI has granted us an exclusive worldwide license to its proprietary ADC technology. We have the right to use this technology, which is based in part on technology licensed by SGI from third parties, to link chemotherapeutic agents to our monoclonal antibodies that target prostate specific membrane antigen and will utilize technology licensed to us from Sloan-Kettering. We are responsible for research, product development, manufacturing and commercialization of all products, and are obligated to make maintenance and milestone payments and to pay royalties to SGI and its licensors, as applicable, on a percentage of net sales. The SGI agreement terminates at the latest of (i) the tenth anniversary of the first commercial sale of each licensed product in each country or (ii) the latest date of expiration of patents underlying the licensed products. We may terminate the agreement upon advance written notice; SGI may terminate if we fail to cure a breach of an SGI in-license after written notice; and either party may terminate after written notice upon an uncured breach or in the event of the other party's bankruptcy.
AE's Report (Cont..)
The initial 12-week clinical trial period of the phase 1 study evaluated up to four intravenous doses of PSMA ADC administered at three-week intervals. Following completion of the four doses, patients were offered, at their physicians' discretion, the option to continue treatment with PSMA ADC for up to an additional 39 weeks. The anti-tumor effect of the compound as measured by changes in PSA levels and number of CTCs was observed in the study across doses ranging from 1.8 mg/kg to 2.8 mg/kg, and durable responses were seen in some of these heavily pre-treated patients. PSMA ADC was generally well tolerated in patients at doses up to and including 2.5 mg/kg. Dose limiting toxicities, primarily neutropenia, were seen at 2.8 mg/kg. The most commonly reported AEs were anorexia and fatigue. Five patients experienced SAEs, two of which resulted in death. One patient dosed at 1.8 mg/kg died from multi-organ failure due to acute pancreatitis: while no data suggested this event was drug-related, a possible relationship could not be definitively ruled out. A second patient died 11 days after receiving study drug at 2.8 mg/kg: septic shock was cited as the cause of death. The investigator considered septic shock as probably related and febrile neutropenia as definitely related to PSMA ADC.
AE's Report (Cont..)
Eight patients experienced serious adverse events (SAEs) which included febrile neutropenia, neutropenia, sinus tachycardia, gastrointestinal disorders, fatigue, infections and dehydration. Two deaths occurred after treatment with PSMA ADC. The first, a patient hospitalized ten days following his first dose of study drug (2.5 mg/kg) with febrile neutropenia and E. coli positive blood cultures, progressed despite treatment to septic shock and died; both the investigator and Progenics considered this patient's septic shock as probably related to PSMA ADC. The second patient developed a rash and fever and was hospitalized for neutropenic fever, where further assessment revealed Strep Viridans bacteria (suspected to be from a tunnel catheter) in blood. Approximately two weeks after receiving study drug (also 2.5 mg/kg), this patient was intubated due to hypoxia and respiratory failure, and died three days after being removed from a ventilator. The investigator considered sepsis as unlikely, bacteremia as probably, febrile neutropenia as definitely related to PSMA ADC; Progenics assessed sepsis as probably, bacteremia as unlikely, and febrile neutropenia as definitely related to PSMA ADC. A third patient died before receiving study drug.
The phase 2 trial was undertaken after review and analysis of results from a phase 1 dose-ranging study of the compound in 52 mCRPC patients whose cancer had progressed despite prior treatment with taxane-based chemotherapy regimens.
AE's Report (Cont..)
PSMA ADC. We are conducting a phase 2 trial of PSMA ADC to assess its anti-tumor activity and tolerability. In this open-label, multicenter U.S. study, participants with metastatic castration-resistant prostate cancer (mCRPC) have received initial doses of drug starting at either 2.5 mg/kg or 2.3 mg/kg; in some cases subsequent doses were adjusted based on tolerability. The study endpoints evaluate the anti-tumor effect of the compound as measured by changes in prostate specific antigen (PSA) levels, number of circulating tumor cells (CTC), pain scores, and tumor size as measured under RECIST criteria. Safety is also being assessed. Progenics announced in December 2013 that it has completed enrollment of 83 chemotherapy experienced patients in this trial and has initiated treatment in an additional trial cohort of up to 35 chemotherapy naive patients who have progressed on hormonal therapies.
Adverse events (AEs) associated with PSMA ADC observed in this phase 2 study through mid-2013 have been consistent with those observed in the phase 1 study noted below; the most common grade 3 or higher AEs in this study have been neutropenia (grade 4: 6.7% at 2.3 mg/kg and 11.4% at 2.5 mg/kg) and peripheral neuropathy (grade 3 or higher: 6.7% at 2.3 mg/kg and 5.7% at 2.5 mg/kg).
Progenics licenses SGEN ADC technology (ADCETRIS) in its phase 2 PSMA ADC Study for Metastatic Castration-resistant Prostate Cancer (mCRPC). The top-line result is scheduled to release at the 2014 ASCO in January. However, there are some AE's related to the drug being used in the trial that including 2 drug related deaths.
Is this a big concern?
Thanks a lot for your time.
As always, thank you very much for your time and kindness to share with us your insights about ICt-107. I am sorry for the off topic in this message board but it may benefit some of us who are invest in both SGEN and IMUC.
With regards to what I have stated in part I of this discussion, I think it is too early to close the book completely on ICT-107. I believe that further observation of the present survivors ( especially those whose disease has not progressed thus far ) in the phase II study is critical. The best case, arguing for a notable survival benefit would be to witness very long term survival limited mostly or almost exclusively to those on the drug rather than those given "placebo" or other standard of care. That observation may not clearly ultimately fall within the realm of "statistical significance" for the present trial as a whole, but may point towards a high degree of potential clinical relevance. This outcome could be explored in an, appropriately, much larger future study with adjusted patient selection, timing of drug administration and more consistent product manufacturing.
In terms of an investment, I consider IMUC to be very high risk and a speculative stock. However, I am a bit ( but not overwhelmingly ) encouraged by insider buying of the shares recently combined with what I have discussed above.
Recently, I have purchased a small bit of shares at about .93 to .95 as a highly speculative investment.......complete loss of capital a distinct and real possibility, with a much lower probability of multiple gains.