The hurdles for Breakthrough Designation are somewhat high as it requires substantial improvement in a clinically significant endpoint over available therapies. The big difference between Breakthrough and Fast Track, is that developers can obtain FT with preclinical data. Likewise when you compared BT with Accelerated, developers can hop on the accelerated path by demonstrating a benefit on a surrogate endpoint that is likely to predict clinical benefit. It doesn't guarantee success, but Breakthrough is rarefied air.
And entering the Breakthrough club today among giants like Genentech, GSK, Pfizer, Merck, Lilly, Amgen, Novartis, BMS, J&J, and Gilead is tiny Immunomedics Inc., who just received Breakthrough approval for IMMU-132. And when I say tiny, I mean teensy. Immunomedics entire market cap (~$200M, after ripping 24% today) is just about equal to Imbruvica's 2014 SG&A net expense.
IMMU-132 (aka sacituzumab govitecan) is an antibody drug conjugate that targets TROP2 to deliver SN-38 (which is the highly potent, active metabolite of irinotecan). Inotuzumab Ozogamicin (an ALL therapy under joint development by Pfizer and UCB) is the only other ADC to have received Breakthrough Designation (which it received last October).
So why is IMMU-132 so important? Well in an aggressive cancer such as TNBC, IMMU-132, as a single agent therapy, demonstrated a significant clinical benefit in a highly pretreated patient population (median of five therapies [range 2-12], including taxanes). According to a release put out by AACR, in which they interviewed Aditya Bardia, MD, MPH of Harvard Medical School, Bardia stated:
"Patients treated with other agents used to treat heavily pretreated metastatic TNBC have a median progression-free survival [PFS] of three to four months in general, while in our phase II clinical trial, patients on IMMU-132 had an interim median PFS of seven months. The response rate to standard agents is usually 10 to 20 percent, while the response rate with IMMU-132 was approximately 30 percent. If you include patients with stable disease, the clinical disease control rate, which is complete response [CR] + partial response [PR] + stable disease, was about 75 percent. Two patients had a CR to treatment, something which is rarely seen in patients with heavily pretreated metastatic TNBC.”And better yet, not only did IMMU-132 produce an interim overall response rate of 31% (by RECIST 1.1) and extend PFS, IMMU-132 did it with minimal adverse events (diarrhea and neutropenia).
Adding to their success in TNBC, Immunomedics has observed similar results in NSCLC, SCLC and UC (although these studies had fewer patients). It's also worth noting that about one year ago Immunomedics received Fast Track Designation for IMMU-132 in TNBC (January 2015), and in May of last year they also received Fast Track Designation for NSCLC. Based on the promising results so far in NSCLC, Immunomedics will likely follow their TNBC success with a Breakthrough Designation in 2016 for IMMU-132 in NSCLC as well.
After 35 years in business, maybe its time teeny-weenie Immunomedics finally gets some love from their brethren. Even if they don't, I love it when the little guy manages to break in and grab a seat at the table. Come to think of it, seat at the trough may be more accurate of late. Knowing how interested they've been in ADC technology (especially safe drugs that work), I scratch my head wondering why the big boys haven't yet snapped up tiny little Immunomedics and its non-toxic ADC.
Perhaps they're worried they'll trample them...