On Friday, December 14, the FDA granted early and accelerated approval of Ariad's (ARIA) further reaching tyrosine kinase inhibitor Iclusig (ponatinib) for the treatment of adult patients with chronic, accelerated or blast phase chronic myeloid leukemia (CML) that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) that is resistant or intolerant to prior TKI therapy.
Inclusig's approval is great news. We have no doubt about it. The drug and the firm behind its creation should be celebrated the same way Gleevec's designers were honored and celebrated when the first tyrosine kinase inhibitor has proven it has, indeed, turned the deadly blood cancers into chronic diseases, saving many lives. This drug, however, couldn't save all the patients. Some did not respond to the drug in the first place, and some of the initial their cancers became resistant to it.
Here comes the role Ariad's drug has demonstrated it can successfully play, i.e., taking care of those patients who are left behind. Inclusig's primary target is BCR-ABL, the same as that of the legendary Gleevec. The difference though is that Iclusig™, which is internally discovered at Ariad, selectively inhibits other tyrosine kinases, including FLT3, RET, KIT, and the members of the FGFR, PDGFR and VEGFR families of kinases. Ariad's early approved drug was designed using Ariad's computational and structure-based drug design platform to specifically inhibit the activity of BCR-ABL. Ponatinib targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation. As a matter of fact, Inclusig is the only FDA-approved TKI that demonstrate efficacy against the T315I mutation.
At the most recent Annual Meeting of the American Society of Hematology (ASH). Ariad presentedtwelve-month follow-up data from the pivotal PACE trial of Inclusig in heavily pretreated patients with resistant or refractory chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The study demonstrated that 56 percent of chronic-phase CML patients in the trial, including 70 percent of patients with a T315I mutation, achieved a major cytogenetic response (MCyR), the primary end-point for chronic-phase CML patients.
Jorge Cortes, M.D., professor and deputy chair, Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX, stated, "These results reinforce Inclusig's impressive anti-leukemic activity in heavily pretreated CML patients, regardless of their mutation status or disease stage." He added, "Ponatinib demonstrated early responses in chronic-phase patients with thirty-four percent of these patients achieving a major molecular response and fifteen percent of those patients achieving a complete molecular response. Of particular importance, responses to ponatinib appear to be durable, with 91 percent of chronic-phase CML patients projected to remain in major cytogenetic response at one year.
When Gleevec was approved for these blood cancers in 2001, the drug was hailed allover the world. The media called it the savior and, like a celebrity, the drug container made the cover of TIME magazine as the "magic bullet" to cure cancer. Those who contributed to the drug received the Lasker-DeBakeyClinical Medical Research Award eight years later, in 2009 and a decade later they were awarded the Japan Prize.
What about those who contributed to the design of development of Inclusig? What about the drug that is bringing hope to the patients who are left behind?
Before dealing with the stock market's reaction on Friday, the day of the drug was approved, which we believe was irrational and irrelevant here are some important facts:
- Inclusig is not a mere addition to a market crowded with drugs, mostly TKI that aim at treating adult patients with chronic, accelerated or blast phase chronic myeloid leukemia (CML). The drug is offering a hope that none of the TKI drugs is able to offer, which is conquering resistant cancers or intolerant to prior tyrosine kinase inhibitor therapy or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) that is resistant or intolerant to the TKI therapies, including those that are newly approved. Indeed, Inclusig works in patients not helped by all targeted and non-targeted available drugs.
"The approval of Iclusig is important because it provides a treatment option to patients with C.M.L. who are not responding to other drugs," Dr. Richard Pazdur, director of the agency's office of cancer drugs, said in a statement. .
- Tasigna from Novartis (NVS) and Sprycel from Bristol-Myers Squibb (BMY) that also aim at inhibiting the same target as Gleevec are also facing resistance. Some cases do not respond to them in the first place.
- Iclusig was approved for all patient who has tried one of the other three drugs without success.
- The FDA not only granted early approved to Inclusig, but approved it three months before the deadline for the early approval. This FDA decision, no doubt about it, demonstrates how urgently important is Inclusig is for rescuing patients not responding to the current treatments.
Important to note that Ariad is conducting clinical trials aimed at getting Inclusig into first line treatment for the indications it has been approved for.
All said, on Friday, the day the drug was approved, instead of rejoicing, Wall street cremated Ariad's stock. Why? They mention the side effects and a warning box that analysts didn't know about. These reasons are totally irrelevant. The adverse effects mentioned related to Ariad's Inclusig are inherent in all tyrosine kinase inhibitors. Indeed, all drugs that end with the suffix tinib, including imatinib (Gleevec) and all other targeted drugs approved for the same leukemias have the same side effects of Ariad's drug Inclusig. These include all hematologic side effects from cytopenia, to neutropenia, thrombocytopenia and anemia. They also have the same cardiovascular and liver side effects.
The good news is that oncologists have become familiar with these side effects and are doing a great job with the help of the patients thanks to education in overcoming them. The warnings in the package inserts have always contributed to the cooperation between physicians and patients towards avoiding, or early managing drugs' adverse effects.
We congratulate Ariad and we are confident that the drug will end up benefiting all patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), in addition to other cancers.
Gleevec generated around $4.7 billion in sales. We believe Inclusig can generate the same.
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