Roundup: 58th Annual Meeting of the American Society of Hematology

Several key pharmaceutical announcements were delivered during the four-day 58^th Annual Meeting of the American Society of Hematology that concludes today in San Diego. Below are some of the major research, trial and data updates presented at the show.

Highlights:

AstraZeneca: Early data demonstrate clinical activity of acalabrutinib in difficult-to-treat chronic lymphocytic leukemia.

Janssen Research & Development, LLC: Data show strong, lasting efficacy of Imbruvica (ibrutinib) through five years of treatment for chronic lymphocytic leukemia/small lymphocytic lymphoma; Daratumumab (Darzalex) combination therapy showed consistent clinical benefit for previously-treated patients with multiple myeloma.

Novartis: Results presented from first global registration trial of CTL019 in pediatric and young adult patients with r/r B-ALL; Data shows treatment-free remission rates are consistently above 50% regardless of reason for switch to Tasigna from Gleevec.

Takeda and Seattle Genetics: Reported positive Phase 3 Alcanza clinical trial data of Adcetris (brentuximab vedotin) for CD30-expressing cutaneous T-cell lymphoma.

Sanofi Genzyme: Announced start of Phase 3 study of Isatuximab for relapsed and refractory multiple myeloma.

Alnylam: Reported positive interim Phase 1 results for Fitusiran in hemophilia A and B patients with inhibitors.

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Details:

AstraZeneca and its hematology Center of Excellence, Acerta Pharma announced preliminary results from the Phase I/II ACE-CL-001 clinical trial of acalabrutinib in subsets of patients with two difficult-to-treat forms of chronic lymphocytic leukemia (CLL), the most common type of leukemia in adults.

The trial includes data from individuals with intolerance to ibrutinib and those with Richter transformation, when CLL transforms into a more aggressive lymphoma. Acerta Pharma chief executive officer, Flavia Borellini, Ph.D., said: “The data at ASH further validate previous clinical trial findings and continue to demonstrate the potential of acalabrutinib in the treatment of B-cell malignancies.”

Acalabrutinib is an investigational, highly selective, potent Bruton tyrosine kinase (BTK) inhibitor shown to minimize off-target activity in pre-clinical studies. The Phase I/II findings presented are part of an extensive and ongoing clinical development program for acalabrutinib in B-cell cancers including CLL, mantle cell lymphoma (MCL), Waldenström macroglobulinemia, follicular lymphoma and diffuse large B-cell lymphoma.

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Janssen Research & Development, LLC announced the longest follow-up results to date of patients treated with Imbruvica (ibrutinib) for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), showing high and lasting responses through five years.

The updated Phase 1b/2 data demonstrated an overall response rate of 89%, including patients with genetic mutations associated with poor outcomes. A complete response (CR) was observed in 29% of patients treated in the first-line setting. Progression-free survival (PFS) was improved with earlier initiation of therapy across treatment-naïve (TN) and relapsed/refractory (r/r) patients.

Janssen also announced new data from two post-hocanalyses of the pivotal Phase 3 POLLUX and CASTOR clinical studies, demonstrating that daratumumab (Darzalex) in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, significantly improved progression-free survival (PFS) and overall response rates for previously-treated patients with multiple myeloma, regardless of prior treatment exposure or cytogenetic risk.

According to a post-hoc analysis of the POLLUX study, daratumumab in combination with lenalidomide (an immunomodulatory agent) and dexamethasone reduced the risk of disease progression or death by 64 percent, compared to lenalidomide and dexamethasone alone, in patients with multiple myeloma who had received one to three prior lines of therapy.

According to a post-hoc analysis of the CASTOR study, daratumumab in combination with bortezomib (a proteasome inhibitor [PI]) and dexamethasone reduced the risk of disease progression or death by 61 percent, compared to bortezomib and dexamethasone alone, in patients with multiple myeloma who had received one to three prior lines of therapy.

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Novartis reported findings from clinical trial ELIANA evaluating efficacy and safety of CTL019, an investigational chimeric antigen receptor T cell (CAR T) therapy, in relapsed/refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL). The global Phase II study found that 82% (41 of 50) of infused patients achieved complete remission or complete remission with incomplete blood count recovery at three months post CTL019 infusion.

For all patients with complete remission, no minimal residual disease was detected. In addition, the estimated relapse-free rate among responders was 60% (95% CI: 36, 78) six months after infusion with CTL019.1. The results set the stage for filing CTL019 with the US Food and Drug Administration (FDA) in early 2017 for pediatric and young adult patients with r/r B-cell ALL.

Novartis also announced new data from the Tasigna (nilotinib) ENESTop Treatment-free Remission (TFR) study, which demonstrate that TFR rates are consistent among Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) patients who switched from Gleevec (imatinib mesylate) due to intolerance, resistance or physician preference. ENESTop evaluated stopping Tasigna treatment in eligible Ph+ CMLadults with chronic phase disease after they achieved and sustained deep molecular response (MR) for at least one year with Tasigna but had not achieved and sustained this response previously with Gleevec.

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Takeda Pharmaceutical Company Limited and Seattle Genetics, Inc. announced data from the Phase 3 Alcanza clinical trial evaluating Adcetris (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL). Topline data were reported in August 2016 demonstrating the Alcanza trial met its primary endpoint of achieving a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4).

Based on the study results, the FDA granted Breakthrough Therapy Designation to Adcetris for the treatment of the most common subtypes of CTCL, mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL). Adcetris is an antibody-drug conjugate (ADC) directed to CD30 which is expressed on skin lesions in approximately 50 percent of patients with CTCL. Adcetris is currently not approved for the treatment of CTCL.

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Sanofi Genzyme, the specialty care global business unit of Sanofi, announced the initiation of the ICARIA-MM Phase III trial of isatuximab, an investigational anti-CD38 monoclonal antibody being studied for the treatment of patients with relapsed and refractory multiple myeloma. The trial will compare isatuximab in combination with pomalidomide and dexamethasone against pomalidomide and dexamethasone. The primary endpoint of the study is progression-free survival. Key secondary endpoints include overall response rate and overall survival.

The initiation of Phase III development for isatuximab is supported by encouraging Phase I and II clinical trial results. The randomized, open label study will enroll 300 patients at trial sites around the world. Isatuximab has been granted orphan designation in the U.S. and European Union.

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Alnylam Pharmaceuticals, Inc., an RNAi therapeutics company, announced positive interim results from Part D of its ongoing Phase 1 study with fitusiran, an investigational RNAi therapeutic, in patients with hemophilia with inhibitors.

New clinical data showed that once-monthly subcutaneous administration of fitusiran achieved lowering of AT and increases in thrombin generation, resulting in a median estimated annualized bleeding rate (ABR) of zero in patients with hemophilia A or B with inhibitors (N=16).

In addition, fitusiran was generally well tolerated through the data cut-off date, October 6, 2016, with no thromboembolic events, including in circumstances when bypassing agents were administered to treat breakthrough bleeding events.

(Sources: AstraZeneca, Janssen Novartis, Takeda, Alnylam, Sanofi, Business Wire, Associated Press)