A few weeks ago, I detailed the two hottest pieces of oncology-related property for Ariad (NASDAQ:ARIA). In that article, I provided an overview of ARIA's technology development in lung cancer, noting that its lead compound, brigatinib, gained breakthrough therapy and orphan drug designation.
But the company surprised me, announcing that it has initiated a rolling NDA to gain approval for brigatinib in patients who are resistant to crizotinib therapy.
In the release, the CEO stated:
"We are ahead of our previously announced schedule for initiating the submission of our brigatinib NDA to the FDA and we are grateful to have breakthrough status from the FDA, which provides the opportunity to utilize the rolling submission process. If approved, we believe that brigatinib will become an important new medicine for ALK+ NSCLC patients who have become resistant or intolerant to prior crizotinib therapy and will offer additional hope to these patients and their families."
The pivotal study results
Ariad will pursue approval of brigatinib on the basis of ALTA, a phase 2 study in patients with crizotinib-resistant NSCLC. Results of ALTA were just presented at this year's ASCO meeting. The overall response rate varied from 46% to 54%, depending on the dosage group. These response rates might be even higher upon further assessment, as several patients in each group had a response that had yet to be confirmed by central review.
Median progression-free survival ranged from 8.8 to 11.1 months in the study. This figure compares well to the published study of ceritinib therapy, which found median PFS of 6.9 months in crizotinib-pretreated patients. Of course, we must be wary of any comparison in a non-randomized context, but it bodes well for the utility of brigatinib.
The only potential hiccup noted by clinicians about brigatinib so far is the risk of a specific adverse event: early-onset pulmonary toxicity. This is uncommon, occurring in 6% of patients in ALTA, and it typically resolves itself in about a week. However, ARIA will need to have a clear plan for clinicians set out to monitor and manage this toxicity, lest it affect the drug's potential approval and subsequent integration into clinical practice.
Potential financial impact of approval
Novartis's (NYSE:NVS) anti-ALK drug, ceritinib, which is approved in the same setting that ARIA is going for, currently nets annual sales of nearly $80 million, and this figure is growing rapidly. The first-line agent crizotinib commands nearly $1 billion in worldwide revenue for Pfizer (NYSE:PFE). If brigatinib is approved for relapsed disease, it will give ARIA the chance to capture some of this market.
Currently, ARIA recognizes around $33 million per quarter in sales revenue, driven almost entirely by its drug for heavily treated CML: ponatinib. Approval of a new kinase in a totally new tumor type will go a long way toward getting the sales figures to the level that investors hoped for back in the halcyon days of 2013, where the company sat at a market cap north of $3 billion.
This NDA is a big opportunity for potential investors. ALK+ NSCLC represents a large market, and patients need more options than the ones they have now. Crizotinib, ceritinib, and alectinib are all good drugs, but inevitably, patients will relapse, oftentimes with resistant mutations.
Brigatinib may provide one more lifeline to patients and ARIA investors alike.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.