My personal hematological oncologist is a "pure clinician." (He doesn't even attend ASH.--LOL) For new drugs and new treatment regimens he told me he looks to Juan Cortes for guidance. He considers Cortes THE thought-leader in hematological oncology. (And all these guys and gals at the top hospitals know one another.) Cortes has been very vocal about the reasons for using Ponatinib in front-line therapy. Another thought-leader, Michael Mauro, is pushing even harder than Cortes. I wouldn't be so quick to deny that Ponatinib has a chance to be used in front-line therapy.
Projections for peak Ponatinib revenues are higher by some analysts than most are projecting here.
Back to Front Page
Ariad: Peak Sales Projections for Ponatinib (Phase III/CML) Could Reach $1.5B; AP26113’s Dual ALK/EGFR
Inhibition Properties Could Expand NSCLC Market Opportunity Four-Fold
Ariad’s (ARIA) R&D day reinforced our belief that ARIA has one of the most compelling emerging oncology pipelines in
all of biotech. We continue to believe that ponatinib (Phase 3 for CML) is the key value driver going forward but that
AP26113 (IND pending for NSCLC) could also evolve into a critical part of the story.
Encouraging physician commentary on ponatinib, consistent with the medical community in general. In his review
of ponatinib, Dr. Michael Mauro from Oregon Health & Science University described the pilot CML data as “quite
outstanding” and also stressed that ponatinib generated better responses in 3rd-line CML patients than the second-gen
TKI’s (Sprycel/dasatinib and Tasigna/nilotinib) showed in 2nd-line patients.
PACE update - a potentially major 4Q11 catalyst. The PACE trial is enrolling well ahead of schedule. This pivotal
study (under an SPA) is now expected to enroll ~400 patients vs. the 320 planned (~51% of patients from N. America,
~36% from EU, and ~13% from Asia-Pac). Enrollment is expected to complete in early 3Q, and the first look at data is
expected at ASH, which we believe will be a major event. Moreover, ARIA expects to file for U.S. and EU approval by
mid-2012, with potential approval in the U.S. by the end of 2012.
ARIA provided guideposts in assessing ponatinib’s market potential. ARIA believes that among new patient starts for
front-line CML, ~20% currently receive a 2nd-gen BCR-ABL inhibitor (either Sprycel or Tasigna) and that this could
grow to ~50% by 2015 (when Gleevec goes generic in the U.S.). With this in mind, ARIA reiterated its global sales
projections for ponatinib in CML/Ph+ ALL of >$600M in yr 5 with use in only resistant/intolerant patients (>$900M at
peak) and >$800M in yr 5 with use in newly diagnosed patients (>$1.5B at peak). These are clearly not risk-adjusted
projections and pricing remains an uncertain yet critical dynamic. That said, these numbers only assume use in the
incidence population and not in the prevalence pop.
AP26113: novel ALK/EGFR inhibitor could be the next leg to this story. ARIA expanded upon the previously
released pre-clinical results for ‘113, a once daily oral drug candidate for NSCLC. Until just Thursday, ‘113 was publicly
thought to be a potent inhibitor of just ALK (same target as PFE’s crizotinib). However, it’s now known to also inhibit the
EGFR T790M mutant that confers resistance to current EGFR inhibitors (a large unmet need). To highlight the
importance of this, ~50% of patients develop resistance to current EGFR inhibitors due to the T790M mutation. In
addition, when tested against the native form of EGFR, ‘113 lacked activity, indicating a favorable selectivity for
activated EGFR which is encouraging as native EGFR inhibition is believed to be associated with toxicity.
Furthermore, several mutations in ALK that confer resistance to crizotinib did not do so with ‘113, including the L1196M
mutation that has been observed in patients who responded to crizotinib but then relapsed. In her presentation, Dr. Alice
Shaw from Mass General stressed that all patients develop resistance to TKIs such as Tarceva (EGFR inhibitor) and
crizotinib (ALK inhibitor), and that ~30% are due to the emergence of a mutation.
AP26113’s dual inhibition properties could expand market opportunity four-fold. As an ALK inhibitor, ‘113’s target
market includes ~4% of NSCLC patients, or ~40,000 patients WW. However, considering the drug’s apparent ability to
target the EGFR T790M mutation in NSCLC as well, another approximate 125,000 patients globally could be theoretical
candidates for ‘113.
We believe AP26113 could have an expedited development pathway, much like ponatinib. ‘113’s IND will be filed
this month, and a Phase 1/2 trial should begin in 3Q11. Even as a new clinical candidate, ARIA stated that pivotal testing
could begin by 2013. In our view, this targeted approach and rapid development path can significantly accelerate the time
to value creation (see ponatinib and crizotinib in addition to products like Incyte’s ruxolitinib). Based on this type of
precedent, we believe ‘113 could be the next big driver for ARIA shares (post ponatinib).
Source: JPMorgan/Kasimov, June 20, 2011
Oncology Indication: Multiple
Keyword: Clinical Trials/Pipeline
Bladerunner
Market Data 
Markets 
AI
