BASEL, Switzerland—Novartis AG announced March 15 thatits investigational compound LDK378 had received breakthrough therapydesignation by the U.S. Food and Drug Administration (FDA) for the treatment ofpatients with anaplastic lymphoma kinase positive (ALK+) metastatic non-smallcell lung cancer (NSCLC) who had progressed during treatment with, or wereintolerant to, crizotinib. Crizotinib is marketed by Pfizer under the brand name Xalkori.
The designation is important—and appropriate—Novartisnotes, as there exist very limited treatment options for patients with ALK+NSCLC, who tend to be non-smokers and younger than NSCLC patients without anALK translocation.
The FDA has indicated that the breakthrough therapy designation is intended to expedite the development and review of drugsthat treat serious or life-threatening conditions if the therapy hasdemonstrated substantial improvement over an available therapy on at least oneclinically significant endpoint. This designation includes all of the featuresof FDA's fast-track program, with the addition of more intensive FDA guidance.The Breakthrough Therapy designation is considered a distinct status from bothaccelerated approval and priority review, which can also be granted to the samedrug if relevant criteria are met, Novartis explains.
"LDK378 is a strong example of our researchapproach, which focuses on identifying the underlying cause of diseasepathways," said Alessandro Riva, global head of oncology development and medical affairs at Novartis Oncology."This breakthrough therapy designation will allow us to collaborate moreclosely with the FDA and potentially to expedite the availability of animportant new treatment option for patients with ALK+ NSCLC."
Initial results from a Phase I study investigatingthe maximum tolerated dose, safety, pharmacokinetics and anti-tumor activity ofLDK378 in 88 patients with ALK+ advanced malignancies and who had progressedduring treatment with, or were intolerant to, crizotinib, showed markedresponses in a majority of patients. According to Novartis, a response rate(including complete response, partial response and unconfirmed partial response)of 80 percent was observed in the patients who had experienced diseaseprogression after crizotinib treatment.
Two Phase II clinical trials are already underwayto further evaluate the compound in this patient population, with plans to beginseveral Phase III clinical trials later this year. First regulatory filing isanticipated by early 2014.LDK378 is one of the at least 14 blockbuster drugs Novartis said in November 2012 that it intends to bring to market by 2017.
NSCLC is the most common type of lung cancer,accounting for as much as 90 percent of all lung cancer cases. Somewherebetween 3 percent and 8 percent of patients with NSCLC have the ALK genemutation.