Jakafi oral side effects Drug Overview, Webb MD
The following common side effects are associated with Jakafi oral:
Abnormal Liver Function Tests; Severe
Decreased Blood Platelets; Severe
Decreased Neutrophils a Type of White Blood Cell; Severe
Why is IMETELSTAT with clearly less effects, certainly none severe set to much higher standards of LFT data procurement by the FDA in the clinical trial requirement phases on ET & MF?
The FDA is clearly complicit in this matter concerning the hold.
"Tefferi of the Mayo Clinic in Rochester, Minnesota, gave follow-up information on the reversibility of hepatotoxicity for all patients who received imetelstat in the MF trial, and the FDA informed him in a letter Wednesday that the trial could continue"
So now that MF1 trial can continue the multi centred larger cohort trial can proceed. The FDA was obviously satisfied by the MAYO's LFT reversibility data and could not further deny a clinical hold in place on MF studies. Reversibility is achievable. One cancer down, how many more to go? JAKI a far inferior treatment was given borrowed time by the FDA when granted approval given it's serious side effects.(approval likely bought and paid for). This lift means GERN will prevail and that IMET can & does save lives; this nobody can deny..
Congrats to all those especially Irish and John that have gone to bat to get this done. Thankyou. And above all fur answer to prayer that this hold will be lifted to enable MF patients to benefit from the treatment.
Now Chippy get off that golf course and into the ball park to get that phase 2 BAT application batting average up to snuff. You need to hit one out of the park. The ferri did his part, now it's your turn.
Well Scarlet finally just came out and said the LFT were such a low grade signal that "you wouldn't notice it unless you were looking for it". This supports what you have been telling us all along about John's response Irish and underlines the stupidity that abounds around this clinical hold. No doubt the JAK1 lobby who were first to notice and alert the FDA to take procedural protocol wrt Hy's Law when in fact this 'slight' elevation appeared to have been overlooked a year or so ago by the FDA ( deemed as insignificant at the time) after receiving previous ET trial data submission. This sudden immediacy on the part of the FDA a considerable time after the fact points to some complicity wrt to the timing of the FDA's hold response. Why now? The irony is that if Jak1 was applying in today's environment based on their limited efficacy and serious side effects they would never had made the FDA grade of approval.
Finally we get some positive signal from management. This calls fur a splish splash!
from geron's press release page: Geron Presents Positive Results from Phase 2 Study of Imetelstat in Essential Thrombocythemia at the American Society of Hematology Annual Meeting
Update on Phase 2 Trial in Multiple Myeloma
"A Phase 2 trial of imetelstat in patients with multiple myeloma was designed to measure the effect of imetelstat on the progenitor cells responsible for the disease. Preliminary data from this trial showed a rapid ad significant decrease in myeloma progenitor cells that were detected in the blood over the course of imetelstat treatment in EIGHT out of NINE patients. In addition, several patients experienced delayed, but sustained, clinical responses as measured by standard criteria. The data have been published in an abstract in the journal, Blood (ASH Annual Meeting Abstracts) 2012 (*they list a link to the publication) Yahoo won't post it. Geron expects that full clinical data from all patients enrolled in the multiple myeloma trial will be available in 2013
"The frequency of circulating MM CSCs (CD19+CD27+ALDH+) was quantified by flow cytometry. Circulating MM CSCs could be detected prior to the initiation of imetelstat (mean 10.7 x 10e3 cells/ml, range 17–53 x 10e3) in 8 of the 9 pts who have completed at least 2 cycles of treatment with imetelstat. In the single remaining patient, circulating CSCs were assessed from Cycle 2 onwards. Over the course of treatment, the frequency of MM CSCs decreased significantly, on average 2 fold every 30 days (Fig 1), in 8 of the 9 patients studied despite no upgrades in clinical response as per IWG criteria. In two pts who received 4 and 6 cycles of single agent imetelstat respectively, standard responses detected as decreasing or plateaued serum M protein or light chain levels were sustained over 4 months following discontinuation (Fig 2). Moreover, these delayed responses occurred in the absence of any additional therapy.
These findings demonstrate that imetelstat rapidly decreases circulating MM CSCs. In addition, several patients experienced delayed, but sustained, clinical responses as measured by standard criteria. Therefore, imetelstat may have therapeutic implications for MM and other malignancies driven by CSCs
hepatotoxicity are not an FDA issue with Jakafi already approved which has shown much higher LFT abnormalities as well as many other toxicity issues than Imet. comparatively.
the MAYO MF trials were with 3rd & 4th stage patients that had no other options. Without seeing all the data Ièm thinking the FDA`s reversal was taking into account the severity of the prognosis weighing it with mild LF elevations that have appeared to be reversible. PV & ET wasn`t in the same category but you`re right in that JAKAFI with many severe side effects is still expanding it`s indication applications to the FDA reaping $billions on a slight reduction in spleen size attribution but has yet to show CR or reversal of the cancer.
INCYE wouldn't require combo therapy if they had a drug that could offer clinical remissions like IMET, soon to become complete remissions without toxic side effects like their lead candidate RUX presently does. With a $20 decline in INCY's SP the current value of GERN should be $20. After phase II or fast tracked BAT designation it will be much higher.
Hay I didn't forget. Those were listed as moderate side effects of Jakafi, not worthy of FDA concerns wrt clinical trials. We won't get into sudden death syndrome and brain lesions caused by Jakafi on this public forum. Could end up becoming targeted road kill critters.
It ticks me off that FDA has apparently no bar set on Jakafi's severe side effects, a drug that has very limited effects on MF cancer patients but yet places an ambiguous low liver function test hold on Imet for far less severe, if any, classified side effects.
Irish needs to start a petition bringing forth the obvious double standard set by the FDA wrt to these two treatments. New MF patients are dying every day this hold is on.
Again Irish thanx fur keeping us critters abreast of John's progress. I do acknowledge your sacrifices in this effort to save his life and others afflicted by this disease. As investors we are driven by a profit motive which if it comes to fruition are bountiful but dwarf in comparison to the gift of extending the life of a loved one. My prayers in the Pugwash Chapel today are fur all the IM patients, the MAYO and fur the powers to be to lift the hold on IMET.
" Imetelstat currently is known to be effective only for high risk patients and not so for low-risk patients" ....how do we know this currently? Imetelstat has only been used on high risk advanced stage patents to date. There have been no low risk studies conducted yet.
... "this hold was about procedure (brought on by politicking behind the scenes?)" No question mark needed BJ. Given all the legal meadow muffins being hurled around currently, if Chippy wasn't dead sure the LFT were of such insignificance he wouldn't have made such a statement. This was clear and encouraging and we needed to see his teeth.
"such a low signal that 'you wouldn't notice it unless you were looking for it". I bet the JAK1 lobby were first to notice and alert the FDA to take procedural protocol wrt Hy's Law when in fact this 'slight' elevation appeared to have been overlooked a year or so ago by the FDA apon receiving previous ET trial data submission. This sudden immediacy on the part of the FDA points to some complicity wrt to the timing of the FDA's hold response . Now come on FDA, tear down this wall and lift this hold!
Squalamine in the verks on cancer, macular degeneration, diabetic retinopathy, and fibrodysplasia ossificans progressiva. Ohr Pharmaceuticals is currently evaluating squalamine in a Phase II study for angiopathic retinopathy (WET AMD) applied topically to the eye. Add Trodusquemine to the pipeline and this becomes a one stop pharma. All that's missing is a breakfast cereal topping....wait I think I have another possible indication.
"Additionally, Squalamine has shown promise in the treatment of solid tumors such as ovarian cancer using the intravenous formulation in significantly higher doses than the eye drop formulation. In a Phase IIa study, patients with stage III and IV refractory and resistant ovarian cancer received Squalamine in combination with carboplatin, with approximately two thirds of the patients achieving a complete response, partial response or stable disease. Squalamine has been awarded Orphan Drug Status by the FDA for the treatment of late stage resistant or refractory ovarian cancer. We expect to publish or present the survival data on the completed phase IIa study in the second half of calendar year 2014 at a scientific conference or appropriate forum. Because of funding constraints, Ohr is seeking a development partner to further advance development of this indication; however we currently do not have plans to enter into such a transaction and there is no assurance that the Company will complete such a transaction"
OPTI's BOARD "we keep it real" ...if you call bashing 24/7 based on your baseless conjectures keeping it real, I hardly think so. Your agenda is to short OHRP and get the SP low as possible or convince retail into selling. With a relatively small float and limited shares traded it becomes an easy target for those that make gains by creating volatility. Your handle showed up when the SP started moving up to $19.99 from which you've played puts and issued calls and although you bring up several concerns on timing, you have not brought up any concrete evidence that squalamine doesn't get to the back of the eye. Livermore has (ad nauseam) dissertated every molecular reaction in the scientific process and gives a pretty convincing argument for supporting the drug's efficacy. His trading advice was not as convincing however and only a fool would believe the lofty price targets he was putting out there. Not to subtract from his enthusiasm, given positive results and no major issues arising, a ten banger in the works is possible. You can accept it or challenge it but with your condescending bashing on anyone or argument contrary to your 'short position' you take personal aim at them or it without substance. Surprise Yahoo lets you get away with it.
Contrary to Liverwurst, if you didn't agree with him he was courteous enough to accept your opposing view. Stewy and Liverwurst would be arguing efficacy for months on end but at least they kept it civil.
You add personal insult in order to add to confrontation. Enjoy talking to yourself, by yourself on your board.
...what big gain? It's merely heading back to where it was bfr the FDA retardedly placed the drug on a full clinical hold.
Are you talking about the already FDA approved treatment Jakafi for MF that shows severe irreversible hematologic toxicity LFT(up to 5x) not to mention irreversible peripheral neuropathy, or irreversible neurological brain MRI?
Imet has not yet shown conclusively it causes low level symptoms nor that these can't be reversed. Of course the FDA is setting the bar much higher for GERN than INCYTE that is experimenting with Jakafi as a breakfast cereal topping