Re: Arzerra (ofatumumab) in rituxan refractory lymphoma

[Guest guest]

Karl

Fresh from the Pink Sheet today.  It still should get approved for CLL this

fall, but who knows how GSK will want to market the drug.  I agree that this

trial should not have expected great results since it is still another antiCD-20

antibody.

 

The NHL trial in 116 refractory patients reported an overall response rate of

just 10 percent in the arm receiving the highest (1,000 mg) dose of Arzerra.

This was well below expectations. Although Genmab never formally announced its

goal for this trial, analysts claim that company executives had mentioned a

hoped-for response rate of 25 percent. And, according to UBS analyst Guillaume

van Renterghem, Wall Street was expecting 40 percent.

This data may affect more than just the drug's prospects in NHL, where Piper

Jaffray analyst Parkes had been forecasting peak sales of up to $800

million. Parkes claims the data may taint physician perception of the drug in

chronic lymphocytic leukemia too, and says it " represents a severe blow to GSK's

marketing plans, " given that data from refractory CLL trials, in his view, had

suggested some differentiation versus rituximab. Jefferies analysts reckon that

oncologists may now be less likely to use Arzerra off-label in other diseases.

Parkes nevertheless still expects FDA approval in CLL, for which the partners

submitted a BLA in January 2009 and for which a PDUFA date - extended by three

months - is set for October 31, 2009. But " CLL is only a small opportunity, "

Parkes said in an interview, adding that he had predicted peak sales in that

indication of just $350 million. Data in fludarabine-refractory CLL, reported

late in 2008, was more promising, showing an almost 50 percent response rate in

previously-treated patients.

From: KarlS@... <KarlS@...>

Subject: Arzerra (ofatumumab) in rituxan refractory lymphoma

nhl-malt , nhl-info ,

nhl-follic , nhl-dlc , MantleCell ,

cns-PAL , ,

PAL-datafork

Date: Monday, August 24, 2009, 6:26 AM

 

re: Genmab shares drop by 35% after a disappointing proof of concept study for

blood cancer drug

Here's a drug that's almost certainly at least as good as Rituxan, but

struggling to find a way to marketing approval. The sponsor chose to test

Arzerra (ofatumumab) in a lymphoma population that was resistant to rituxan -

the same class of drug. Why? Because this is where the clinical need is - or

more accurately, the marketing opportunity.

What was the " proof of concept " ? That this or any anti-cd20 drug could provide

clinical benefit in patients refractory to another anti-cd20 drug. An ambitious

(or foolish) inquiry with an irony: radioimmunotherapy (radio-labeled anti-cd20)

has already proven itself able to do just that, convincingly. This exploration

of next generation cd20 mabs being yet another signal that companies do not find

radioimmunotherapy appealing as a drug product ... from a marketing perspective.

~ Karl

Patients Against Lymphoma

Non-profit | Independent | Evidence-based

www.lymphomation. org

[Guest guest]

re: Interesting report today on Veltuzumab, the " other " 2nd-generation

CD20 Mab. Seems like a pretty good result in a difficult-to-treat

population. Perhaps the difference is that the patients in this study were

not entirely comprised of people refractory to rituxan?

http://www.allbusiness.com/pharmaceuticals-biotechnology/pharmaceutical-agents/1\

2714230-1.html

==

Thanks for commenting. I expect so and consider the term

" relapsed/refractory " population to mean any patient in need of second or

third line therapy ... that sponsors tend to use the word " refractory " too

liberally, particularly in press releases.

We could hope that one of the half-dozen next-gen cd20 antibodies will

deliver when Rituxan fails, but I wouldn't bet the farm on it.

More likely (just opinion) some next-gen cd20s will provide equal --- to

signficantly better activity in those who would benefit also from rituxan,

perhaps with less risk of reactivity-based toxicity (being humanized).

To win approval based on superiority of the new anti-cd20 to Rituxan (in

Rituxn naive patients) would take a randomized controlled study -- a very

expensive and time consuming venture.

It would be good (assuming equivalence or better) to have at least some of

the next-generation anti-cd20 antibodies reach the market so that we can

have competition drive down costs .. in the way that generic drugs drive

down costs when the drug patent expires (coming soon for Rituxan). Noting

that producing generic prorducts for biologics, like Rituxan, might not be

as feasible as it is for chemical drugs.

The second path to approval is to select a population with an unmet medical

need- the truly refractory. That's what was tried with Arzerra in

Rituxan-refractory FL (and it failed to deliver), but also in high-risk CLL.

The company could well win approval for CLL based on the outcome in that

study ... In such refractory populations a head-to-head randomized study is

not required to win accelerated approval.

~ Karl

cc: Other lymphoma support lists because this topic might be of general

interest. Note: Full names and email removed from this reply to protect

privacy

Subject: [nhl-follic] Re: Arzerra (ofatumumab) in rituxan refractory

lymphoma

Interesting report today on Veltuzumab, the " other " 2nd-generation CD20

Mab. Seems like a pretty good result in a difficult-to-treat population.

Perhaps the difference is that the patients in this study were not entirely

comprised of people refractory to rituxan?

http://www.allbusiness.com/pharmaceuticals-biotechnology/pharmaceutical-agents/1\

2714230-1.html

" This is a multicenter phase I/II dose-finding study in relapsed/refractory

B-cell non-Hodgkin's lymphoma (NHL) evaluating veltuzumab, a humanized

anti-CD20 antibody with structure-function differences from chimeric

rituximab. Eighty-two patients (median age, 64 years; 79%stage III/IV, one

to nine prior treatments) received four once-weekly doses of 80 to 750

mg/m(2) of veltuzumab. "

" Veltuzumab was well tolerated, with no grade 3 to 4 drug-related adverse

events despite short infusion times (typically 2 hours initially, 1 hour

subsequently at doses < 375 mg/m(2)). In follicular lymphoma, 24 (44%) of 55

patients had objective responses (OR), with 15 (27%) complete responses

(CRs) or CRs unconfirmed (CRus) by International Working Group criteria, and

with some responses occurring despite two to five prior rituximab-containing

regimens, less favorable prognosis (elevated lactate dehydrogenase, tumors >

5 cm, and Follicular Lymphoma International Prognostic Index >= 2), and at

all dose levels.The CRs/CRus were durable (median duration, 19.7 months),

with five patients still ongoing (15.9 to 37.6 months duration). "