Ariad’s (NASDAQ:ARIA) drug Taltorvic (ridaforolimus) is a novel small-molecule inhibitor of the protein mTOR interferes with cell growth, division, metabolism and angiogenesis. The FDA independent committee will discuss, debate and decide whether this drug should, or should not be approved for metastatic soft tissue sarcoma or bone sarcoma whose disease has not progressed after at least 4 cycles of chemotherapy.
The FDA has posted on its website the following question for its committee:
Given the small differences in median progression-free survival (NYSE:PFS) and overall survival (OS) between arms, the adverse event profile of ridaforolimus, and its positioning as a maintenance therapy in patients with soft tissue and bone sarcoma, is the risk-benefit assessment favorable for the use of ridaforolimus in the treatment of patients with soft tissue and bone sarcoma who have received prior chemotherapy?
Before we speculate over the committee’s decision on Taltorvic, we must bear in mind that the drug is not the only mTOR inhibitor drug that exists. Three mTOR inhibitor drugs have already reached the market in the US. The first is sirolimus (Rapamune), developed by Wyeth for the prophylaxis of organ rejection for ≥13 years old patients receiving renal transplants. There has been some off-label use of this drug. The second mTOR inhibitor drug, everolimus (Afinitor) developed by Novartis (NYSE:NVS) for advanced renal cell carcinoma (RCC) in patients who have been treated unsuccessfully with other medications. Afinitor is also approved for subependymal giant cell astrocytoma (SEGA), a brain tumor seen with a genetic condition called tuberous sclerosis (NYSE:TS). It is for patients who need treatment but are not candidates for curative surgery. A third mTOR inhibitor is temsirolimus (Torisel) developed by Pfizer (NYSE:PFE) and approved for advanced, relapsed renal cell carcinoma.
With regard to the upcoming FDA committee’s meeting, we believe that the approval or denial of approval of this drug will not depend in its entirety on the drug’s side effects alone. The side effects are almost exactly the same as those of the three-mTOR inhibitors that have already been granted approval for various cancers. From the clinical trial results’ point of view, the drug has technically met the PFS endpoint. Considering the fact that no drug exists for the category of patients targeted for treatment with Taltorvic, we are persuaded that the PFS trials’ results, regardless of how modest they might be, are sufficient for approval. Afinitor, the mTOR inhibitor developed by Novartis was granted approval in spite of the fact that while it shrank the tumor, it failed to demonstrate Improvement in disease-related symptoms and in survival. This fact would probably cross the committee members’ minds, insinuating that the presence of mTOR inhibitors, including Taltorvic’s on the market is badly needed and should be considered a plus, rather than a minus.
As a matter of fact, oncologists in top prestigious cancer centers, including Sloan Kettering Cancer Center have expressed terrible need for new drugs that can fill the treatment void in post chemo soft tissue and bone sarcoma. The question becomes: Are there any reasons to believe that Ariad’s/Merck’s drug Taltorvic might actually offer opportunity to fill the void oncologists believe must be urgently filled? The committee should also consider the future use of the drug in combination regimens that can expand its efficacy and increase its safety. If the drug were marketed, the decision upon this consideration will not be restricted to Merck and Ariad, but dictated by the experience oncologists would gain treating thousands of patients. Oncologists’ familiarity with new drugs tremendously raises the odds for a successful pinpointing the best combination regimens that makes the drug safer and more effective.
What about in case the committee votes against approval?
Responsible investors are familiar with Ariad’s product pipeline and their promises. They are aware of Ariad’s decision to file for ponatinib’s approval in the second half of this year and that the approval of the drug is expected early next year. The broad potential of penatinib is well demonstrated in results from clinical trials in patients with chronic myeloid leukemia (CML) or Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), who are resistant or intolerant to dasatinib or nilotinib or who have the T315I mutation. Important to know that Ariad is alone on this drug and will not have to share the revenues.
Having said that, we believe that in case the committee votes against the approval of Taltorvic, we expect investors’ negative reaction to be minimal. Our strategy in this case is not to let the opportunity slip. We will accumulate ARIA at the lower price.
Disclosure: We Long ARIA.