Pfizer’s failure provides clarity for Arqule

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Yesterday Pfizer (PFE) announced that Sutent failed to prolong survival of lung cancer patients when given in combination with Tarceva. The drug led to an increase in progression free survival (PFS), which was the secondary endpoint of the study. The results are not published and there are several open questions such as the extent of PFS improvement, benefit across different subtypes and use of Sutent in patients from the placebo cohort after progressing on Tarceva. Nevertheless, chances to see Sutent+Tarceva  as a standard of care for 2nd/3rd  line NSCLC are slim.

Pfizer’s failure provided some clarity for Arqule (ARQL) and its partner Daiichi Sankyo, who plan to initiate a phase III study for ARQ-197 in combination with Tarceva. The indication Arqule is pursuing is very similar to that pursued by Pfizer, so had the Sutent trial been successful, it would have adversely affect ARQ-197’s prospects in general and potentially the required clinical route.

Although the Sutent study does not have a direct impact on the performance of ARQ 197 in the pivotal trial, it could have made things more complex. For instance, positive results could create a new standard of care, with direct implications on study design and availability of patients. As ARQ-197 trial design is being negotiated with the FDA for the sake of obtaining a special protocol assessment (SPA), a new standard of care might force Daiichi and Arqule to change the study as well as patient recruitment.

This demonstrates the inherent risk in drug development and how biotech companies can be affected by events on which they have no control whatsoever. In this case, it seems that the Sutent trial was the last phase III study evaluating an investigational agent for NSCLC in combination with Tarceva. Sutent joins the long list of drugs that did not show benefit in combination with Tarceva in lung cancer, including Avastin, Nexavar and multiple chemotherapy drugs. In that sense, Arqule is facing a great challenge, but unlike other drugs that failed, it is armed with a good (albeit not perfect) efficacy signal from a randomized phase II trial.


Pfizer’s pipeline of targeted therapies has experienced multiple setbacks recently. Sutent’s failure in lung cancer comes just several months after the discontinuation of another phase III trial in liver cancer. Earlier this year, Pfizer said it was postponing activity with tanezumab in osteoarthritis. Pfizer also terminated two phase III studies with its IGF1-R antibody, figitumumab, in lung cancer in late 2009 and early 2010, respectively.

One ray of light in Pfizer’s oncology pipeline is crizotinib, which is on its way to fast approval in a genetically defined subset of NSCLC patients. Another promising drug is tasocitinib, a JAK inhibitor with pivotal rheumatoid arthritis data expected at ACR this November. On top of the efficacy issue, a lot of attention will be given to the side effect profile of the drug. Incyte (INCY), who is also developing a JAK inhibitor but with a different selectivity profile will be affected by Pfizer’s data, but in this case, Incyte investors should hope for positive data from Pfizer.


19 thoughts on “Pfizer’s failure provides clarity for Arqule

  1. Thank you so much for this. I bought a few chares of ARQL today. It’s a bargain. Not to belabor the point, but have you checked out CHTP lately, which I mentioned a couple of times? I sold it at $4. Happy hunting.


  2. Sorry JR, I don’t follow CHTP. Looks liky they have an important binary event next month.

    Sam, I think you brough up a good point so I’ll try to tackle it anyway. Yes, ARQ-197 did not meet the predefined primary endpoint but unlike the Sutent study, Arqule’s phase II was not a registration trial and was intended to generate a signal. It indeed generated some interesting signals such as a stat sig improvement in non-squamous patients as well as an improvement in OS (which was just a trend). Even if you look at the entire population, factoring in imbalances which are validated wrt Tarceva response, the data looks positive.
    If ARQ-197 doesn’t meet the primary endpoint in the phase III study which will hopefully be balanced and optimally designed then we can say the drug failed as well.



  3. The fact ARQ 197 generated such an OS signal is even more impressive given the fact 40% of the control arm crossed over to receive the combination. btw, a handful of crossover patients achieved actual tumor shrinkage, which is also a nice indication.I doubt the p3 trial will allow patients to cross over.



  4. Hello Ohad,

    you mentioned the JAK inhibitor of INCY. Have you an opinion to the JAK inhibitor CYT398 of YM BioSciences? They say their data is consistent with INCY’s 18424, has an improved selectivity and a favorable side effect profil.

    Regards Toby


  5. Toby,

    It is hard to say. I guess that they are seeing activity and a reasonable safety profile but their data is still early and limited (and unpublished). JAK looks like a great arena but don’t forget there are plenty of active programs and companies like YM will probably have to face at least one established JAK inhibitor in the market.
    You now have Sanofi,Onyx and AZN in the race as well, so YM will have to differentiate their product.



  6. Ohad, FDA just rejected fast track of TDM1…pushed back to mid 2012…what’s your analysis on this announcement? Is there still promise in TDM1 and IMGN’s guided missile technology? Thanks.


  7. In the short run -very bad news
    In the long run – no meaningful effect as the phase III trials are more important for T-DM1’s commercial success.

    This rejection doesn’t mean anything in terms of the value of IMGN’s technology.

    Will try to publish something next week



  8. hello ohad,

    what stocks are you personally long in the portfolio?

    In the seekingalpha article you disclosed that you were long arql, phizer, and incy (of course those were the only bio’s mentioned in that article).



  9. sam, I don’t want to clog Ohad’s blog with too much off-topic posts, so you’re welcome to email me at I don’t have a lot of positions and nothing changes very often — so I don’t even use computers that much and check email about once or twice per week. Best regards. JR


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