Mining ASCO 2018's Gold, Part 12: Let's Talk About Blood, Baby

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Includes: ABBV, GILD, JNJ, SNY, TGTX
by: Zach Hartman

Summary

Today we take a very brief tour into the wide world of heme malignancies.

Interesting developments from big pharma could spur competition, particularly in myeloma.

TPT subscribers gained exclusive access to a discussion on an under-the-radar anti-B-cell drug.

Welcome to "Mining ASCO 2018's Gold," a series dedicated to helping you identify upcoming investment gems in biotech based on under-reported studies being presented at this year's big cancer meeting.

But first, did you happen to miss any of the previous editions? If so, please do give them a look!

Note: These articles come in groups of 4, but subscribers to the Total Pharma Tracker got an exclusive extra. So that's 10 potential investment ideas that you're missing out on if you are not a member. Join today for a free two-week trial!

TG Therapeutics’s PI3K drug appears to work even if patients have failed on prior PI3K inhibitor treatment

Abstract 7530 - A phase 2 study to assess the safety and efficacy of umbralisib (TGR-1202) in pts with CLL who are intolerant to prior BTK or PI3Kδ inhibitor therapy

Chronic lymphocytic leukemia (CLL)

TG Therapeutics (TGTX)

One of TGTX’s main contenders in hematologic malignancies is the next-generation PI3K-delta inhibitor called umbralisib. As most of us recall, toxicity sidelined Gilead’s (GILD) entry into this space, idelalisib. But TGTX hopes to pick up where GILD failed, testing umbralisib specifically in patients who were intolerant to prior BTK inhibitor (i.e., ibrutinib) or PI3K inhibitor therapy. 40 patients were enrolled in the study, 10% of whom ultimately discontinued due to adverse events. However, no patients discontinued therapy as a result of an adverse event that caused them to stop prior therapy.

Furthermore, after 6.5 months of treatment (at the median), 90% of patients remained progression free, giving a favorable sign that umbralisib is also re-establishing disease control. This is an interesting first: patients who failed on a PI3K inhibitor wouldn’t normally be considered for an alternate version, but this study seems to support that it is feasible and potentially effective if you make the right switch. It’s still early days for this strategy, but I think it’s encouraging!

Outlook: Neutral to positive

AbbVie looks to move its CLL tag team to the combo realm

Abstract 7502 - Phase 2 CAPTIVATE results of ibrutinib (ibr) plus venetoclax (ven) in first-line chronic lymphocytic leukemia (CLL)

Chronic lymphocytic leukemia (CLL)

AbbVie (ABBV)

ABBV is currently on track to rule the roost when it comes to targeted therapy in CLL treatment. The company has two drugs considered potential best-in-class in ibrutinib and venetoclax. Its drugs are the de facto standard of care for a lot of patients. But what happens when you put them together? This phase 2 study asked that question. A total of 163 patients were provided both drugs at the same time, and during the safety run-in, no dose-limiting toxicities were observed in 14 patients, and all 14 achieved a response. By leading in carefully with ibrutinib, then venetoclax, tumor lysis syndrome was avoidable in this study. Moreover, many of these patients also achieved minimal residual disease elimination.

These are very encouraging results, overall, but it is disappointing to see no analysis of the larger data set, which was not presented at ASCO. Oh, well. This would probably have been a much higher-profile study, and we can consider it a taste of things to come. Could ABBV own the first-line standard of care come 2019?

Outlook: Positive

Sanofi sells a gem in relapsed multiple myeloma

Abstract 8038 - Final results of a phase Ib study of isatuximab (ISA) plus pomalidomide (Pom) and dexamethasone (dex) in relapsed/refractory multiple myeloma (RRMM)

Multiple myeloma

Sanofi (SNY)

SNY has a bead on Johnson & Johnson’s (JNJ) growing power in multiple myeloma, thanks to its outstanding CD38 antibody daratumumab. But what no one seems to know is that SNY also has a CD38 antibody on deck called isatuximab. And at ASCO 2018 it reported findings from a phase 1 study combining this agent with pomalidomide and dexamethasone in relapsed/refractory multiple myeloma.

A total of 45 patients were enrolled in the study. And the treatment was generally well-tolerated, with perhaps the most worrisome adverse event being high rates of severe neutropenia, but this did not lead to a major increase in serious infections. Moreover, the overall response rate was 62%, which is similar to what has been observed in a similar study investigating daratumumab.

SNY considers these results highly encouraging, and it means that a competitor may soon be nipping at the heels of JNJ in this space. And a phase 3 trial to confirm these findings is ongoing.

Outlook: Positive

AbbVie poises to break venetoclax into myeloma therapy?

Abstract 8004 - Phase 2 study of venetoclax plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma

Multiple myeloma

AbbVie (ABBV)

To date, in spite of the general nonspecificity of Bcl-2 function in cancer cells, ABBV has yet to make a break with venetoclax outside of the strict confines of CLL. And this is a shame, because the drug has a lot of promise in a number of cancer types, particularly the hematologic malignancies. This phase 2 study enrolled 26 patients with relapsed multiple myeloma to undergo standard carfilzomib-dexamethasone along with venetoclax.

Overall, the therapy combo was well-tolerated, with no dose-limiting toxicities being reported in the study. Grade 3/4 neutropenia and hypertension were the most common high-grade toxic events, and this may grow higher if the number of patients exposed to the drug was increased. Out of the 17 patients who could be evaluated for response, 8 achieved some form of response, and another 3 had stable disease.

These findings provide an interesting efficacy signal for ABBV’s investigational combo. We need more data before we draw a firm conclusion, but this one is definitely not DOA, and the study continues to enroll patients.

Outlook: Neutral

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.