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BioCentury Extra
As published Tuesday, December 06, 2016 6:56 PM PST


  • BCMA-targeting therapies in ASH spotlight

    At the American Society of Hematology meeting in San Diego, presentations late Monday highlighted data from Phase I studies of two candidates targeting tumor necrosis factor (TNF) receptor superfamily member 17 (BCMA; TNFRSF17; CD269) to treat multiple myeloma. One was a chimeric antigen receptor (CAR) T cell therapy from Novartis AG (NYSE:NVS; SIX:NOVN), and the other an antibody-drug conjugate (ADC) from GlaxoSmithKline plc (NYSE:GSK).

    Data showed that depth of responses to Novartis' CART-BCMA correlated with degree of T cell expansion. Among six evaluable patients, the therapy led to one stringent complete response (sCR) ongoing at seven months, one very good partial response (VGPR) that progressed after five months, and two minimal responses (MR). There was one case of stable disease (SD) and one progressive disease (PD). The sCR and VGPR patients achieved peak T cell counts of 174,110 and 220,081, respectively, compared to 302 cells in the PD patient.

    Five patients experienced cytokine release syndrome, including two grade 3 events. Researchers reported one case of dose-limiting toxicity that included severe delirium, recurrent seizures, obtundation and cerebral edema. All six patients expressed BCMA, but the trial did not require pre-specified expression levels. Patients had received a median of nine prior therapies. The candidate is an autologous T cell product engineered by lentiviral transduction to express a human BCMA-specific CAR with CD3z and 4-1BB signaling domains.

    In a separate study in which 24 patients were evaluated for efficacy, GSK's GSK2857916 led to one VGPR, three PRs, and two MRs. Eight patients remain on treatment, while 14 discontinued due to disease progression. There were eight serious adverse events in six patients, including one case of unresolved limbal stem cell deficiency that investigators considered drug-related. No dose-limiting toxicities were reported, although four patients required dose reduction due to adverse events.

    The study evaluated MM patients who were previously treated with alkylators, proteasome inhibitors, immunomodulators and stem cell transplantation, if transplant eligible, and who had documented disease progression on or within 60 days of last therapy. GSK2857916 is a humanized IgG1 anti-BCMA antibody conjugated to the microtubule disrupting agent monomethyl auristatin-F via a stable, protease-resistant maleimidocaproyl linker.

    Last week, bluebird bio Inc. (NASDAQ:BLUE) said its anti-BCMA cell therapy, bb2121, produced a 78% overall response rate among nine evaluable patients, with two stringent complete responses. Celgene Corp. (NASDAQ:CELG) and bluebird share rights to the autologous T cells transduced ex vivo with an anti-BCMA-2 CAR lentiviral vector delivering the CAR targeted to BCMA (see BioCentury Extra, Nov. 30).

  • GNS identifies disease drivers from CoMMpass data

    GNS Healthcare Inc. (Cambridge, Mass.) said it has identified four genes as "top drivers" of high-risk multiple myeloma. Using its machine learning technology, the company is collaborating with the Multiple Myeloma Research Foundation (MMRF) to analyze data in the foundation's patient-driven, real-world CoMMpass study.

    GNS said the four are cyclin dependent kinase 1 (CDK1; CDC2); maternal embryonic leucine zipper kinase (MELK); protein kinase, membrane associated tyrosine/threonine 1 (PKMYT1); and NIMA-related kinase 2 (NEK2). The company also said its analysis showed that targeting certain translation elongation factors and ribosomal genes may drive durable responses in MM. It presented its results at the American Society of Hematology (ASH) meeting in San Diego.

    Launched in 2011, CoMMpass is studying 1,000 newly diagnosed, treatment-naive patients. MMRF is collecting sequential tissue samples to identify how patients' molecular profiles affect clinical progression and treatment response (see BioCentury, Dec. 14).

    According to ClinicalTrials.gov, the Astex Pharmaceuticals Inc. subsidiary of Otsuka Pharmaceutical Co. Ltd. (Tokyo, Japan) and the MMRF have completed a Phase II study of AT7519, an inhibitor of of CDK1, CDK2, CDK4, CDK5 and CDK9, alone and in combination with Velcade bortezomib in previously treated MM patients. Takeda Pharmaceutical Co. Ltd. (Tokyo:4502) and Johnson & Johnson (NYSE:JNJ) market Velcade.

    GNS said MELK inhibitor OTS167 from OncoTherapy Science Inc. (Tokyo:4564) has shown "a synergistic effect" with other MM treatments, but has not yet been tested clinically for the disease. According to ClinicalTrials.gov, the candidate is in a Phase I/II study to treat multiple leukemias.

  • New data out for Btk inhibitors Imbruvica, acalabrutinib

    Data presented at the American Society of Hematology (ASH) meeting in San Diego showed response rates for Bruton's tyrosine kinase (Btk) inhibitors Imbruvica ibrutinib to treat graft-versus-host disease (GvHD) and acalabrutinib (ACP-196) to treat chronic lymphocytic leukemia (CLL).

    Johnson & Johnson (NYSE:JNJ) and AbbVie Inc. (NYSE:ABBV) market Imbruvica. AstraZeneca plc (LSE:AZN; NYSE:AZN) and Acerta Pharma B.V. (Oss, the Netherlands) are developing acalabrutinib.

    In a Phase II study, J&J said Imbruvica led to an overall response rate (ORR) of 67% among 42 evaluable GvHD patients who failed prior systemic therapy. At a median of 14 months of follow-up, nine patients had a complete response and 19 had partial responses. Among the responders, 20 (71%) had a sustained response of at least five months. Imbruvica is a Btk inhibitor that covalently binds to cysteine residue 481.

    Separately, AZ and Acerta reported data from the Phase I/II ACE-CL-001 trial in patients with relapsed or refractory CLL who were intolerant to Imbruvica and patients with Richter transformation of CLL. Among the study's 33 evaluable Imbruvica-intolerant patients, acalabrutinib led to an ORR of 79%. Median progression-free survival (PFS) had not yet been reached. Among 21 evaluable patients with Richter transformation of CLL, acalabrutinib led to an ORR of 38%, with a median PFS of 2.1 months. Median duration of response was 5.2 months.

    In a June 2016 investor presentation, AstraZeneca said acalabrutinib had led to an overall response rate of 85% in a Phase I/II study to treat relapsed or refractory CLL, and 88% in a Phase I/II study to treat first-line CLL.

    Acalabrutinib is a second-generation Btk inhibitor.

  • AZ reports Tagrisso's PFS benefit in NSCLC

    Newly announced data from the Phase III AURA3 trial of Tagrisso osimertinib from AstraZeneca plc (LSE:AZN; NYSE:AZN) showed that the drug improved progression-free survival (PFS) by 5.7 months vs. chemotherapy in patients with non-small cell lung cancer.

    Tagrisso has accelerated approval from FDA to treat EGFR T790M mutation-positive, locally advanced or metastatic non-small cell lung cancer patients who progressed on or after an EGFR tyrosine kinase inhibitor (TKI). The drug is conditionally approved in the EU to treat NSCLC in EGFR T790M mutation-positive patients, irrespective of previous EGFR TKI treatment.

    The company described the trial as confirmatory. Spokesperson Makini Nyanteh declined to say whether the company believes the new data are sufficient to gain full approval from regulators, or to give a timeline for submission.

    AURA3 evaluated Tagrisso in the second-line setting. The drug led to a PFS of 10.1 months vs. 4.4 months for doublet chemotherapy (HR=0.3; 95% CI: 0.23, 0.41; p<0.001), meeting the study's primary endpoint. Tagrisso also significantly improved objective response rate (ORR), a secondary endpoint (71% vs. 31%, p<0.001). Overall survival (OS) data are not yet mature.

    Data were presented at the World Conference on Lung Cancer in Vienna and published in the New England Journal of Medicine. AstraZeneca said in July that Tagrisso had met the study's primary endpoint, but the company did not release detailed data at the time (see BioCentury Extra, July 18).

    Tagrisso is an oral irreversible inhibitor of EGFR-activating mutations and the T790M EGFR resistance mutation.

  • Gladstone launches Tenaya with $50M series A round

    The Gladstone Institutes said it launched cardiovascular newco Tenaya Therapeutics Inc. (San Francisco, Calif.) with a $50 million series A round. Tenaya President JJ Kang told BioCentury that The Column Group contributed about $48 million to the tranched round, while angel investors provided the balance. Kang is also an associate at The Column Group.

    Kang said Tenaya is aiming to develop two platforms to treat heart failure. It intends develop gene therapies to regenerate heart muscle through cellular reprogramming. It will also seek to discover small molecule candidates to treat heart failure via multiple disease models. She said both platforms are in discovery stages, and declined to give a timeline for clinical studies.

    Tenaya scientific co-founders include Gladstone investigators Benoit Bruneau, Bruce Conklin, Sheng Ding and Saptarsi Haldar, plus Eric Olson from the University of Texas Southwestern Medical Cener.

    Gladstone said Tenaya is the first company formed from its BioFulcrum initiative, which is designed to bring together scientists, non-profits and industry partners to speed drug development.

    Kang and The Column Group's David Goeddel joined Tenaya's board.

  • SillaJen slips in first trading day

    SillaJen Inc. (KOSDAQ:215600) lost W2,150 (14%) to W12,850 in its first day of trading Tuesday after it raised W150 billion ($135 million) through the sale of 10 million shares at W15,000 in an IPO.

    The company is conducting a Phase III trial of Pexa-Vec pexastimogene devacirepvec to treat advanced liver cancer. The therapy is a recombinant vaccinia virus that expresses GM-CSF and lacks thymidine kinase.

  • Oxford Biodynamics ticks up after IPO

    Biomarkers company Oxford Biodynamics plc (LSE:OBD) gained 1p to 159p in its first day of trading Tuesday. Last week, the company raised L7.1 million ($8.8 million) through the sale of 4.5 million shares at 158p. Existing investors raised L12.9 million ($15.9 million) through the sale of 8.2 million shares in a concurrent private placement.

    Based on the offering price, Oxford Biodynamics had a postmoney valuation of L136 million ($167.8 million). Stifel was the placement agent.

    Oxford Biodynamics develops epigenetic biomarkers using its EpiSwitch platform.

  • Vermont releases drug pricing report

    In its first report since the passage of a new price transparency law, the Vermont Attorney General's office identified drugs with substantial increases in wholesale acquisition cost (WAC). The document named three branded therapies -- EpiPen, Prevacid lansoprazole and Humira adalimumab -- with triple-digit percentage increases from 2012-16.

    The report, produced in consultation with the Department of Vermont Health Access (DVHA) and the Green Mountain Care Board (GMCB), is required under legislation signed into law in June (see BioCentury Extra, June 3).

    DVHA and GMCB identified eight branded drugs and two generics whose WAC increased by at least 50% over the last five years or at least 15% over 12 months, and on which the state spends a "significant" amount. The largest price hike was attributed to generic doxycycline from Mutual Pharmaceutical Co. Inc. (Philadelphia, Pa.), with a 4,788% increase over five years. EpiPen's WAC rose 205% over the same time period, Humira's 114% and Prevacid's 103%, the report said.

    The report included comments from drug manufacturers that WAC does not reflect rebates, discounts or price concessions, but said increasing WAC does not always result in higher rebates. The authors added that the uninsured "often bear the full burden of price increases at the pharmacy."

    Mylan N.V. (NASDAQ:MYL) markets EpiPen. Price increases for the epinephrine auto-injector have attracted national attention. Takeda Pharmaceutical Co. Ltd. (Tokyo:4502) markets Prevacid, and AbbVie Inc. (NASDAQ:ABBV) markets Humira.

  • Gene Editing Becoming a Strategic Consideration

    Leaders across the life sciences industry are beginning to realize that they must quickly get up to speed on the potential disruptions gene editing will bring to the industry. Having a ready means of silencing, activating, correcting, or even replacing individual genes will undoubtedly scramble the strategic maps of many companies. Triangle Insights has prepared a white paper that identifies nine aspects of the emerging gene editing market landscape that should be considered by life sciences strategy teams tasked with anticipating the impact that rapid development of gene editing techniques will have on their businesses. Click here to download the white paper.


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