It will be a separate infusion and packaged separately. The dates and times are going to be different than those for the other chemo drugs.
Off label use doesn't really happen in oncology with chemo. But if PEG has the kind of success we anticipate, there will be LOTS of studies using it in all kinds of combinations that patients can get into before formal approval for those indications.
... and realize that Celgene's success, from Revlimid to Abraxane, and everything inbetween, came from acquiring companies with cancer products they recognized as blockbuster, not from internal development.
Background: Poor outcome in pancreatic cancer (PDA) has been associated with tumor stroma limiting access of chemotherapy drugs. PEGPH20 (PEG), PEGylated recombinant human hyaluronidase, which depletes hyaluronan (HA) in tumors, has demonstrated anti-tumor activity in preclinical PDA models. In a KPC model of PDA, PEG + gemcitabine (Gem) significantly prolonged survival compared to Gem alone. In Phase 1 PEG monotherapy studies, the MTD was 3µg/kg. The most common adverse events (AEs) were musculoskeletal events. Methods: This was a phase 1b study to determine the recommended phase 2 dose of PEG + Gem in patients (pts) with previously untreated Stage IV pancreatic cancer. PEG was given at 1, 1.6, or 3µg/kg IV twice weekly Wks 1–4 and weekly Wks 5–7, followed by 1 wk rest. Gem was given at 1000mg/m2IV once weekly for Wks 1–7, then 1 wk rest. Thereafter, PEG + Gem were given once weekly for 3 wks in 4-wk cycles. Dexamethasone was given pre and post PEG doses. Due to evolving SOC, the study was discontinued before initiation of the phase 2 randomization. Results: Twenty-eight pts were enrolled in the study. The majority of the patients (89%) had metastatic sites in the liver. Four, 4 and 20 pts received PEG at 1, 1.6 and 3µg/kg, respectively. The most common AEs related to PEG were muscle spasm (54%), myalgia (39%), arthralgia (29%), peripheral edema (29%), fatigue (25%), and extremity pain (18%). Median progression free survival (PFS) and overall survival (OS) were assessed and were 154 and 200 days, respectively. In an exploratory analysis, tumor biopsies from 17 pts were evaluated for HA levels (HAhigh or HAlow). 6 pts were determined to have HAhigh tumors and 11 pts had HAlow tumors. The median PFS and OS for HAhigh pts were 219 days (95% CI: 159-276) and 395 days (95% CI: 210-578). For HAlowpts median PFS and OS were 108 (95% CI: 14-163) and 174 days (95% CI: 34-293). Conclusions: PEG + Gem is generally well tolerated in advanced pancreatic cancer and shows promising clinical activity, especially in pts with HAhigh tumors. ClinicalTrials.gov Identifier: NCT01453153.
It will be, but don't count on much in the way of revenues. There is no "moat" with diagnostic testing. If they charge too much, any other company can replicate the test with a little research.
The investigators in the PCRT team have developed a therapeutic regimen which attacks both the tumor compartment and the stromal compartment of pancreatic cancer and induces complete responses in a small percentage of patients with advanced stage IV pancreatic cancer.
The gemcitabine + nab-paclitaxel regimen had outstanding activity in a 67 patient phase I/II trial with all patients at the recommended phase II doses (n=44) having a decrease in CA19-9, some complete responses and a median survival of 12.2 months. The proposed regimen that is devised for this study is a bold, innovative approach with the specific aim of utilizing a relentless pursuit approach to try to make the complete response rate 70% and have this response be durable (which the PCRT has defined as lasting at least 6 months) and to dramatically enhance the percent of patients who survive one year (try to make the rate 70%).
The induction regimen the investigators propose collapses the stroma (gemcitabine + nab-paclitaxel) and addresses the use of a non-cross resistant active regimen (FOLFIRINOX) as a consolidation regimen. Both should improve the chance of driving tumor markers down dramatically. The investigators think that FOLFIRINOX with the stromal collapse induced by the initial regimen, plus the totally non-cross resistant shot against the disease (consolidation), will maximize the chance of achieving a complete response with an attendant improvement in survival.
After the consolidation, the patient will be maintained on a less toxic targeted therapy selected by molecular profiling plus the use of the antimetabolomic agent metformin which has consistently been associated with better survival in multiple retrospective studies (Jiralerspong et al., 2009).
I think maumar on the iHub board found the trial. Unfortunately, it doesn't use PEG.
There is a ton of doubt. So much about what is described in the lay press doesn't add up.
The investigator is up to his neck in cancer vaccine research. PEG is not in trials with those.
There isn't ten in any PEG cohort.
There isn't any plans to present data on PEG in Philly this year.
There isn't a PEG study that includes follow on maintenance with any of the trial drugs.
PEG isn't associated with personalized genetic testing in any trial yet.
That PEG is being used in the same institution this pt is being treated in isn't enough. The "barrier treatment" quote is suggestive but too general to overcome the above descrepancies, IMO.
That said, tomorrow will be very interesting for many other reasons.
"Phil Zeblisky is one of 10 people involved in the clinical trial. Borazanci said that the results will be announced in April at a medical conference in Philadelphia"
Phil is also part of another new clinical study that tests the effectiveness of maintenance therapy."
Doesn't sound like PEG
I would love to know if the agreement with J&J precludes Merck from using HALO technology also if Remicade is one of the drugs. A little light on how the royalties and milestones are structured would be nice. The Q&A on the next CC should be full of such questions.
I'm happy they did. The J&J partnership should also help with future PEG collaborations.
I believe it is still a good negotiating tacit for HALO to engage with the generic competitors.
Well, it is an example to express the main idea that HALO has options to expand on their SC delivery platform.
The reason Remicade might be a good candidate is that, even in the face of the SC competition I listed, Remicade IV is still a blockbuster because it is a better drug than the others.
South Korea's Celltrion is one such company. I believe they have about a $3-4 billion market cap and have solid revenues. There is no reason why HALO needs to limit its partnerships to big pharma to help them fend off biosimilars. Of course, Roche might not really appreciate HALO partnering with someone who is also trying to copy Herceptin and Rituxin. But the threat that HALO might take its technology to the competition might help to motivate big pharma to cut some deals now.
Can you do something beside ask dumb questions? Bring a fact or an idea to us please. At least read more carefully the post your are responding to.
I don't propose HALO get into the biosimilar business. I propose. HALO negotiate with the companies already producing the Remicade biosimilars. If I were HALO, I'd go knocking at their door with Prezi in hand showing them how they can steal business away from J&J faster than simply offering a cheaper version. Offer to skip the upfront and milestone payments and, perhaps, kick in a little developmental cash in exchange for a much larger percent of sales revenue.
It is a 2.5 hour IV infusion every 4 to 8 weeks, for a variety of immune mediated inflammatory conditions, that sells about $9 billion per year for J&J and Merck. Biosimilars are going thru Europe's approval process now. European and U.S. Patents end in 2015 and 2018 respectively. Now would be a good time for HALO to get involved. The market for SC Remicade is nearly certain.
For most of these diseases, patients are started on the home use of the SC drugs, Enbrel and Humira. When these fail, the superior antibody, Remicade is used. Imagine the temptation to use Remicade earlier when it also can be given at home.
If J&J and Merck aren't interested, perhaps one of the biosimilar companies would be.
The old 10% igsc uses about a third more product than the IV or Hyqvia. Not sure, but I believe that would be the same for the new 20% solution.
So, when comparing conventional SC to Hyqvia, fezz is correct, it uses more IG product. Sorry if I missed that implication. I just don't think conventional sc competes AT ALL because of the dosing frequency. It is the IV use that is far more common and it is current IV users that will be switching to Hyqvia if market share is to grow.
The Ig dose is the same, 300-600mg/kg/month, regardless if IV or Hyqvia.