Source : Medical Technology Stock Letter
report from September 27, 2012
We have just discovered a major positive protocol change in the ibrutinib Phase II clinical trial for multiple myeloma that has increased our confidence not only for the upcoming ASH meeting but also for the drug’s potential in multiple myeloma:
THE CHANGES ARE SIGNIFICANT –
a) BIG INCREASE IN THE SIZE OF THE STUDY - The trial has been expanded from 35 patients to 164 patients, an almost 5-fold increase.
Why is this meaningful? As the company stated it would expand the study from the initial cohort of 13 patients, expectation were that the trial would then move on to the next 13 patient cohort. By raising the sample size this much is an extremely encouraging sign that there is activity in single agent ibrutinib in relapsed/refractory MM.
b) THREE MORE ARMS ADDED - The number of arms has also been increased from one to four:
ibrutinib 420 mg per day (the original protocol)
ibrutinib 560 mg per day + 40 mg dexamethasone once per week
ibrutinib 840 mg per day
ibrutinib 840 mg per day + 40 mg dexamethasone once per week
The addition of oral dexamethasone is important as when it was combined with CELG’s pomalidomide, the drug increased response rates from 9% as a single agent to roughly 30% in combination with dex. In addition, preclinical trials of ibrutinib in MM have suggested synergy in combination studies. Raising the ibrutinib dose is, in our view, a smart move that might result in greater efficacy, as the side effect profile is so clean. (Reminder, the company tried 840mg in CLL only to show similar efficacy at 420mg). So, we believe there is activity in MM at 420mg but could be greater at a higher dose and with dex.
c) REGISTRATION STRATEGY BEGINNING TO EVOLVE - Adding to our enthusiasm is the fact that MM drugs can be approved on Phase II data when they show they have an effect on refractory patients. In a major unexpected decision, ONXX’s Kyrpolis was recently approved on Phase II data – with a 22% single agent activity, poorly tolerated drug (esp. compared with ibrutinib). Celgene has copied the strategy and will go in front of an FDA advisory panel with Phase II data in refractory MM on November 7. PCYC has yet to comment on its regulatory strategy for MM, but this trial is clear evidence of the company’s aggressive move forward.
d) WHAT TO EXPECT AT ASH? While we have no idea exactly what the company will present at ASH, we are confident that the efficacy hurdle rate of 22% (the ONXX Krypolis response rate) has been met. Coupled with the much cleaner side effect profile, in our view ibrutinib will be a very competitive drug to treat refractory multiple myeloma. Because there are 3-4 registration trials starting and/or underway in other B-cell indications, the company is likely to remain conservative in its MM disclosures. And while we doubt the above study will qualify for a registration study, in our view, investigators will be eager to replicate that early data in larger studies like the above changes include.
This is important new information that, while still early, the Street has yet to report on and that PCYC stock has yet to reflect. The potential in MM represents a very large additional market opportunity for ibrutinib and the release of abstracts and Phase II data at ASH could drive the stock close to our $105 target. We again reiterate our BUY limit of $70 and remind subscribers to read the BLOOD article, the above clinical trial(s) and be fully invested before the abstracts are released on November 5.
On a technical note, the stock has bounced off support after touching 70 in early September and dropping briefly below 60 last week – a healthy pullback. With the above news and upcoming catalysts, in our view, the stock should resume it upward momentum.
Source: Medical Technology Stock Letter,
Ordinarily I would say today's trading on the basis of early results of a Phase 1 dose finding study is silly. But given the expectations built by this thread, it's probably good to get these wild expectations out of the system.
Ibrutinib takes time to work and has some weird manifestations. Even in CLL, Ibrutinib can take a long time to see clinical benefit, which is preceded by apparently worsening blood cell counts as cancer cells leave the lymph noded and enter the blood stream.
Excellent post. They also added a secondary endpoint (DCB) and a warfarin use exclusion.
DCB is defined as the time from first confirmed response of Minor Response or better to first progressive disease or death.
It's hard to imagine a conclusive finding 6 months after opening the trial. So I'm not as positive yet. But the new endpoint suggests they already have at least minor responses on the timer. My bet is most patients are still on ibrutinib and we'll see something like the early CLL results (100% still on treatment).