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.
Its always a concern when a drug does not meet its primary endpoint, which is the case of ICT-107 in the initial readout of the phase II trial results.
My purely "gut" feeling is that ICT-107 does prolong survival in certain patients with GBM but only considering the following:
The vaccine when administered must elicit a strong immunologic response. In particular I am still unsure if the product used in the Phase II study was precisely identical in terms of method of manufacture as compared to the Phase I drug. Also, administration very close to the time of chemotherapy could possibly blunt the immune response needed to offer survival benefit.
There may be a lag time ( a "long tail" ) before the full effect may be seen. The problem is that with a disease as aggressive as GBM some patients, unfortunately, will not survive long enough to experience the benefit of what is essential a "slow acting" drug.
The patient's tumor must have the target or targets that match the antibodies or cellular response which are being stimulated by the vaccine. In the case of ICT-107, we don't yet have the analysis of the tumor antigens in the trial and how they correlated with patient PFS or OS.
Because of the "long tail" of the immune system stimulation response ( as noted above ) there may be patients in a particular trial cohort who, indeed, do survive for much longer periods or potentially experience dramatic survival improvement. However, one has to wait much long to document this effect. In these longer term survivors one can then correlate their tumor antigens and level of immune response and use this information to compare with the larger trial population. ......and then possibly use this information in future patient selection. ( part II of the response to follow )
Nhan knows that I follow this SGEN board closely, so he placed his question here knowing that I would see it. Thanks, in advance, for your understanding of the reason for the brief off topic discussion here.
Do you have any concerns about ICT-107 that shows a statistically significant increase in progression-free survival among patients suffering early stages of the aggressive brain tumor type glioblastoma multiforme but fails to hit statistical significance in overall survival for the intent-to-treat population? Given that the OS is the primary end point.
Thanks a lot for your time!
My expectation has long been that until 1/14 the stock was shackled to $40 by LEAP OPEX. However pressure built so much that advance knowledge of the news coming on at the JPM conference on 1/13 begun blowing the lid off a couple of days in advance but SP was successfully if hardly contained just above the $40 watermark. With 1/14 gone, PPS are now steaming ahead presaging more upbeat news to be disclosed at the 2/11 CC. The smoke signs for good things to come were pretty clear from significant open market purchases from at least 2 significant tutes holders and trading patterns seem to imply that such buys are still ongoing while what was ~ 13 million shares short at last count, are panicking to cover ahead of the dreaded 2/11. My expectation was that SP would be between $55 and $60 around the Q4 CC date and while it may have looked a little looney at the time of first disclosure does not look much so right now.
Looking ahead to mid to late summer, barring an overall market meltdown, I'm anticipating that data from other ongoing trials (the HL over 60 in particular) will begin the percolate out from under the lid and the SP will melt up to the $ 80 to $ 100 zone.
Just my unqualified opinion.
It's not $9M in royalties--those are just the milestone payments.
SGEN pps did very well this week--hoping there won't be too much backsliding next week.
See the posts below regarding the SGEN presentation at JP Morgan's conference on Monday. Lots of upbeat information, suggesting many upcoming positive catalysts. Stock has been doing very well nearly every day since that presentation.
I bought back in 2003. Glad to see this stock is starting to pay off my loyalty. But 9 million in royalties sure does not seem like a lot, or not enough of a catalyst to spur the stock as it did today. Is there more news?