Tag Archives: ASH2013

The other side of drug development

dwtf_lgBringing a new drug to market is very expensive. There is a lot at stake and investors follow the process closely. For the record, Monday morning biotech stock market quarterbacks or financial analysts are driving my nuts. When I try to research drug development news and updates, there is probably 10 articles by these market analysts for every 1 clinical or scientific one. It’s like search engine SPAM. This one came to my inbox this morning and is almost depressing. ASH 2013 just wrapped up a week ago. There are no good , effective FDA approved treatments for my particular chromosomal mutation. For me, this drug IPI-145 seems to be working miracles in managing my disease but to the analysts, it’s too little too late in a market that seems to be getting crowded in recent months.

Why Investors Are Writing Off Infinity Pharma

Looking back to the beginning of 2013 it was thought that Infinity had the best in class PI3K inhibitor and the development lead held by Gilead could be overcome with better efficacy. ASCO threw a giant wrench in that thesis as many started to worry about the higher rates of serious infections (although this is another story as the rates were similar to idelalisib.)  Regardless of whether the rates were higher or not, the fact was IPI-145 was no longer seen as a clearly better drug. Thus the development lead of Gilead became a much larger hurdle.

ASH was the chance to present additional data that highlighted both the improved efficacy of IPI-145 and allay concerns over the rate of infections. Given the extremely negative sentiment, this seemed like a good contrarian bet (assuming good data). In many ways, IPI-145 held up its end of the bargain as the data were fine but the stock continues to sell. Why?

The issue was that many saw the data as good as, but not obviously better than, idelalisib. The consensus was that it was not nearly enough to overcome the development lead and commercial experience of Gilead. As such, sentiment went beyond negative.  How can sentiment move beyond extremely bearish? It moves into indifference and that was what I detected at ASH. People wrote off IPI-145.

Way to ruin a good thing. Fooey on you guys!

Infinity Pharmaceuticals, Inc. – News Release

Feels like I’m part of an elite club.


IPI-145 Data in Patients with CLL The presentation, “Preliminary safety and efficacy of IPI-145, a potent inhibitor of phosphoinositide-3-kinase-δ,γ, in patients with chronic lymphocytic leukemia” (Abstract #677), included 67 patients evaluable for safety and 47 evaluable for clinical activity. Among the 67 patients enrolled in the study, 52 had advanced disease and had progressed during or were refractory to, intolerant of, or ineligible for established therapy. An additional 15 treatment-naïve patients were enrolled who were age 65 or over or high-risk, defined as having 17p deletions or p53 mutations.Clinical ActivityUpdated data from the ongoing Phase 1 study showed that IPI-145 is clinically active in patients with relapsed/refractory CLL. Treatment with IPI-145 at doses ≤ 25 mg BID in patients with relapsed/refractory CLL led to a nodal response rate of 89 percent and an overall response rate of 48 percent as defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria1, including one complete response and 12 partial responses among 27 patients evaluable for response. The median time to response was less than two months. Seventy-five percent of patients (six of eight) treated for 12 months or longer remain progression-free on treatment.Among 12 patients evaluable with 17p deletions or p53 mutations who received IPI-145 at doses ≤ 25 mg BID, there were six partial responses, five patients with stable disease, and one disease progression due to Richter transformation. Patients with CLL with 17p deletions or p53 mutations generally have a poor response to chemotherapy and worse prognosis.2 Preliminary data in treatment-naïve patients showed a reduction in adenopathy in all six patients. Three of these six patients had nodal responses, including nodal responses in two patients with p53 mutations.

ASH 2013


The ASH 2013 (American Society of Hematology) annual meeting kicks off in New Orleans today. There will be many presentations; this one I am most eagerly awaiting. It presents current data on the Infinity Pharmaceuticals ipi-145 clinical trial I am enrolled in. The presenter, Dr Ian Flinn is my Hematologist/Oncologist. You can read the full abstract here. Here’s a tidbit.

#677 Preliminary Safety and Efficacy Of IPI-145, a Potent Inhibitor Of Phosphoinositide-3-Kinase-δ,γ, In Patients With Chronic Lymphocytic Leukemia

Program: Oral and Poster Abstracts
Type: Oral
Session: 642. CLL: Therapy, excluding Transplantation: Clinical Trials of B Cell Receptor Signaling Inhibitors
Monday, December 9, 2013: 5:30 PM
295-296 (Ernest N. Morial Convention Center)

Ian Flinn, MD, PhD1, Manish Patel, MD1,2*, Brad S. Kahl, MD3, Steven M. Horwitz, MD4, Francine M. Foss, MD5, Yasuhiro Oki, MD6, Pierluigi Porcu, MD7, Jennifer Sweeney, BS8*, Kerstin Allen, MA8*, Kerrie Faia, MS8*, Patricia Harris, MPH8*, Joi Dunbar, PharmD8*, Howard M. Stern, M.D., Ph.D.8*, Patrick Kelly, MD8 and Susan O’Brien, MD6

Clinical activity has been observed in R/R CLL pts at all doses of IPI-145 studied from 8 mg to 75 mg BID and in pts with R/R high-risk disease (TP53 mut/17pdel).  Treatment-related lymphocytosis is rapid, with the median ALC return to baseline within 6 cycles of treatment.  Reduction in adenopathy occurs early with no apparent dose-dependence.  Nodal responses (>50% reduction in adenopathy by CT assessment) occurred in 79% of pts after 2 treatment cycles.  Best overall response (based on investigator assessment per IWCLL) in evaluable pts to date (median [range] number of cycles 5.1 [1-21.1]) is 52%, with 1 CR, 15 PR, 14 SD and 1 PD. The ORR for the 19 evaluable pts treated at ≤25 mg BID is 53% (10/19; including 1 CR) and 7 of the 8 SD pts achieving nodal response.  Resolution of lymphocytosis may lead to an increase in best ORR for SD pts who remain on study.  R/R pts with high-risk disease (TP53 mut/17pdel) had similar ORR.
Conclusions:  IPI-145, an oral, potent PI3K-δ,γ inhibitor, appears well tolerated and has shown promising clinical activity in pts with R/R CLL across the range of doses examined.  The PK/PD and clinical activity suggest that 25 mg BID is a biologically active dose in R/R CLL, and this dose has been selected for an upcoming randomized Phase 3 trial in R/R CLL. Updated data from treatment-naïve CLL pts who received IPI-145 at 25 mg BID and R/R CLL pts who received IPI-145 at 25 mg and 75 mg BID will be presented.