Daiichi Sankyo (OTCPK:DSKYF)(OTCPK:DSNKY) initiates a three-part open-label Phase 1/2 study assessing U3-1402, an HER3-targeting antibody-drug conjugate, in patients with treatment-resistant HER3-positive metastatic/unresectable breast cancer.
US-1402 will administered as an intravenous infusion every three weeks. Part 1 will assess the safety, tolerability and maximum tolerated dose, Part 2 is a dose-finding phase and Part 3 (Phase 2) will assess the efficacy of the recommended dose. The primary objectives are safety and the response rate over ~six months.
According to ClinicalTrials.gov, the estimated final data collection date for the primary endpoint is September 2018. The estimated study completion date is December 2018.
Under the terms of the deal, Kite will receive $50M upfront, up to $200M in milestones and low-to-mid-double-digit royalties.
Daiichi has a certain amount of time to license additional products, including T cell receptor candidate KITE-718. Kite can earn up to $200M in milestones for each candidate licensed.
Axicabtagene ciloleucel is an investigational therapy in which the patient's T cells are genetically modified to express a CAR (chimeric antigen receptor) that targets the CD19 antigen, a protein expressed on the surface of B-cell lymphoma and leukemia cells. This enables the T cells to locate and kill the cancer cells.
The FDA approves Teva Pharmaceutical Industries' (NASDAQ:TEVA) generic version of Daiichi Sankyo's (OTCPK:DSKYF)(OTCPK:DSNKY) TRIBENZOR (olmesartan medoxomil, amlodipine, hydrochlorothiazide) for the treatment of hypertension. Final launch preparations are underway.
The company recently launched its generic version of Daiichi's AZOR (amlodipine and olmesartan medoxomil) in the U.S.
Enrollment is underway in a Phase 3 clinical trial, QuANTUM-First, assessing Daiichi Sankyo's (OTCPK:DSKYF)(OTCPK:DSNKY) orally available quizartinib for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who have a genetic mutation called FLT3-ITD, which occurs in ~30% of AML cases. The mutation is associated with more aggressive cancer, characterized by a higher relapse rate and reduced overall survival (OS).
QuANTUM-First is a double-blind, placebo-controlled study that will randomize ~536 patients to receive either quizartinib plus induction and consolidation chemotherapy or placebo plus induction and consolidation chemo. The primary endpoint is event-free survival (EFS) at Year 2. Secondary endpoints include OS at Year 2, complete remission rate (CR) at the end of the first induction cycle (Day 42), composite CR at the end of the first induction cycle and the percentage of patients achieving CR with no evidence of minimal residual disease (Day 42).
According to ClinicalTrials.gov, the estimated final data collection date for the primary endpoint is January 2020.
Quizartinib, acquired via the September 2014 acquisition of Ambit Biosciences, is a small molecule inhibitor of FLT3-ITD (FMS-like tyrosine kinase-3-internal tandem duplication), a growth driver of abnormal cells that contributes to the development of AML. It has Orphan Drug status in the U.S. and Europe.
Exelixis (EXEL +3.1%) announces that its partner Daiichi Sankyo (OTCPK:DSKYF)(OTCPK:DSNKY) has initiated a phase 3 pivotal trial evaluating CS-3150 (esaxerenone (r-INN)), an oral, non-steroidal, selective mineralocorticoid receptor antagonist, for the treatment for essential hypertension in Japanese patients. As a result of Daiichi Sankyo enrolling the first patient in the trial, Exelixis is eligible for a $15M milestone payment, which it expects to receive in Q4.
The ESAX-HTN phase 3 pivotal trial is a randomized study of CS-3150 versus eplerenone in Japanese hypertensive patients. The 18-week trial will enroll an estimated 930 patients into three treatment arms: 2.5 mg and 5 mg doses of CS-3150, and 50 mg of eplerenone.
In March 2006, Daiichi Sankyo and Exelixis entered into a research collaboration agreement to discover, develop and commercialize novel therapies targeting the mineralocorticoid receptor (MR).
In addition to ESAX-HTN, Daiichi Sankyo is sponsoring six smaller phase 3 clinical trials of CS-3150 in specific populations of patients with hypertension.
CS-3150 is one of the compounds identified during Exelixis’ research collaboration with Daiichi Sankyo during March 2006. Under the terms of the agreement, Exelixis granted Daiichi Sankyo an exclusive, worldwide license to certain intellectual property primarily relating to compounds that modulate MR. In exchange, Exelixis received a $20M upfront payment, research funding for a joint research period, and the potential for substantial clinical development, regulatory and commercialization milestone payments, as well as double-digit royalties on sales.
Portola Pharmaceuticals (NASDAQ:PTLA) plummets 18% premarket on increased volume in response to its announcement that it received a Complete Response Letter (CRL) from the FDA regarding its Biologics License Application (BLA) seeking approval of anticoagulant reversal agent AndexXa (andexanet alfa).
The company says most of the requested information relates to manufacturing although the agency also wants more data to support inclusion of edoxaban [Daiichi Sankyo's (OTCPK:DSKYF)(OTCPK:DSNKY) Savaysa] and enoxaparin [Sanofi's (NYSE:SNY) LOVENOX] in the label. It also stated that it needs more time to complete its review of the clinical amendments to Portola's post-marketing commitments that were submitted recently.
Andexanet alfa is a modified human Factor Xa molecule that acts as a decoy to target and sequester, with high specificity, Factor Xa inhibitors in the blood. Once bound, the Factor Xa inhibitors are unable to inhibit Factor Xa and normal hemostatic processes are restored.
Management will host a conference call this morning at 8:30 am ET to discuss the situation.
Amgen (NASDAQ:AMGN) inks an exclusive deal with Tokyo-based Daiichi Sankyo (OTCPK:DSKYF)(OTCPK:DSNKY) to commercialize nine biosimilars in Japan, including adalimumab [AbbVie's (NYSE:ABBV) Humira], bevacizumab [Roche's (OTCQX:RHHBY) Avastin] and trastuzumab (Roche's Herceptin).
Under the terms of the agreement, Amgen will be responsible for development and manufacturing and Daiichi will manage regulatory submissions and handle distribution and commercialization while Amgen will have a limited rights to co-promote the products.
Amgen will retain all distribution and commercialization rights outside of Japan. Financial terms are not disclosed.
Nektar Therapeutics (NASDAQ:NKTR) enters into an agreement with Daiichi Sankyo Europe (OTCPK:DSKYF)(OTCPK:DSNKY) granting Daiichi European rights to ONZEALD (etirinotecan pegol) (NKTR-102), currently in Phase 3 development for advanced breast cancer.
Under the terms of the deal, Nektar will receive an upfront payment of $20M, up to $60M in milestones and double-digit royalties on net sales in Europe. Daiichi will have exclusive rights in Europe, Switzerland and Turkey while Nektar will retain rights in the U.S. and the rest of the world.
Nektar plans to file a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) next month seeing conditional approval of ONZEALD for the treatment of advanced breast cancer and brain metastases. The review will be under an accelerated timeline. Conditional approval, renewed annually, may be granted in cases where there is an unmet medical need in patients with a severely debilitating disease. The company will be responsible for sponsoring and funding the confirmatory trial that will support the MAA filing for ONZEALD in Europe. The data will also be used in an NDA filing in the U.S.
ONZEALD is a long-acting topoisomerase I inhibitor which is designed to concentrate the drug in tumors. The elimination half-life of etirinotecan is 37 days compared to two days for irinotecan but with peak SN38 (active metabolite of irinotecan) levels 5 - 10 times less which improves the tolerability profile.
Aviragen Therapeutics (NASDAQ:AVIR), formerly Biota Pharmaceuticals, raises $20M in new capital via the sale of a portion of the royalty rights to Inavir to HealthCare Royalty Partners. It intends to use the proceeds to advance its pipeline of direct-acting antivirals to treat infections that have limited treatment options.
Inavir, an inhaled neuraminidase inhibitor approved in Japan for the treatment and prevention of influenza, is the leading flu treatment there. It is marketed by Daiichi Sankyo (OTCPK:DSKYF)(OTCPK:DSNKY).
Chinese biotech BeiGene (BGNE -2.9%) reports positive data from an ongoing Phase 1 clinical trial assessing product candidate BGB-283 in patients with BRAF or KRAS/NRAS-mutated cancers who have not responded adequately to prior treatments (one to six prior lines of therapies). The data were presented at the 2016 American Association for Cancer Research Annual Meeting in New Orleans, LA.
At the time of the data cutoff, there were 29 evaluable patients. One receiving a 40 mg starting dose had a confirmed complete response, two patients receiving a 20 mg or 30 mg starting dose had confirmed partial responses and 15 patients had stable disease (no progression), implying a disease control rate of 79% (n=23/29).
The most frequent mild-to-moderate (grade 1 or 2) treatment-related adverse events were fatigue (52%), thrombocytopenia (low blood platelets)(39%), decreased appetite (39%), hand-foot syndrome (redness/swelling in hands and/or feet)(35%), acne (32%) and hypertension (32%). Serious treatment-related adverse events (grade 3 or 4) observed were thrombocytopenia (13%), fatigue (10%) and liver enzyme (ALT) elevation (10%).
BGB-283 is called a RAF dimer inhibitor which has shown activity against the RAF family of kinases, including ARAF, BRAF, CRAF and BRAF V600E. It can potentially address resistance to first-generation BRAF inhibitors. For example, vemurafenib, discovered b Daiichi Sankyo (OTCPK:DSKYF)(OTCPK:DSNKY) and marketed by Roche (OTCQX:RHHBY +1.4%) under the brand name Zelboraf, achieves only a 5% response rate in BRAF V600E-positive colorectal cancer.
BeiGene is currently conducting all clinical development for BGB-283. It retains all rights to the candidate in China while Merck KGaA (OTCPK:MKGAF)(OTCPK:MKGAY) has exclusive rights ex-China.
Portola Pharmaceuticals (NASDAQ:PTLA) licenses lead development and commercial rights in Japan to andexanet alfa to Bristol-Myers Squibb (NYSE:BMY) and Pfizer (NYSE:PFE) to be developed as an antidote to anti-coagulants apixaban and other Factor Xa inhibitors. In a separate deal, the company enters into a clinical collaboration agreement with Bayer HealthCare (OTCPK:BAYRY) to include its Factor Xa inhibitor rivaroxaban.
Under the terms of the agreement with BMY and PFE, Portola will receive an upfront payment of $15M, milestones up to $90M and double-digit royalties. Under the Bayer deal, Portola will receive an upfront payment of $5M and an undisclosed milestone based on regulatory approval. BMY and PFE own exclusive commercial rights.
Three Factor Xa inhibitors are currently available in Japan, BMY and PFE's apixaban, Bayer's rivaroxaban and Daiichi Sankyo's (OTCPK:DSKYF)(OTCPK:DSNKY) endoxaban. No antidote is approved, however.
Oral anticoagulants are a $800M market in Japan. A antidote is needed in certain situations such as emergency surgery, trauma or episodes of uncontrolled bleeding.
As expected, the European Commission approves Roche's (OTCQX:RHHBY +1.5%) Cotellic (cobimetinib), in combination with Zelboraf (vemurafenib), for the treatment of adults with unresectable or metastatic BRAF V600 mutation-positive melanoma.
Cobimetinib, co-developed with discoverer Exelixis (EXEL +1.1%), inhibits an enzyme called mitogen-activated protein kinase kinase (MEK), a mediator of downstream signaling of tumor growth factor receptors. Vemurafenib is a BRAF inhibitor that was discovered by Daiichi Sankyo's (OTCPK:DSKYF)(OTCPK:DSNKY) Plexxikon unit.
In a regulatory filing, ArQule (NASDAQ:ARQL) discloses that it has exercised its option with development and commercialization partner Daiichi Sankyo (OTCPK:DSKYF)(OTCPK:DSNKY) to co-commercialize lead product candidate tivantinib in the U.S. as allowed under their December 2008 Agreement (subject to FDA approval). A separate co-commercialization agreement should be inked in Q1.
Tivantinib is currently being evaluated in a Phase 3 study, METIV-HCC, as second line treatment of liver cancer [hepatocellular carcinoma (HCC)]. The primary endpoint is overall survival. According to clinicaltrials.gov, the estimated final data collection date for the primary endpoint is March 2017. The estimated study completion date is June 2017.
If METIV-HCC is successful and tivantinib is cleared by the FDA, ArQule will receive $55M in milestone payments for the official acceptance of its marketing applications in the U.S. and EU. for the second line treatment of HCC. It will earn an additional $100M in combined milestones based on FDA clearance and the first commercial sale in the UK, Germany, France, Italy or Spain. The total milestone payments of $155M will partially offset the $75M - 85M that ArQule owes Daiichi for the costs of the Phase 3 trial. ArQule also expects to earn sales-based royalties of 20%.
Pexidartinib is an orally available small molecule drug that selectively inhibits a primary growth driver of abnormal cells in the synovium (thin layer of tissue lining the joints and tendon sheaths) that causes TGCT called colony stimulating factor-1 receptor (CSF-1R).
TGCT is a rare non-metastatic tumor that affects the synovium-lined joints, bursae and tendon sheaths causing swelling, pain, stiffness and reduced mobility. Its prevalence is 11 cases per million.
Breakthrough Therapy status provides for more intensive guidance from the FDA, the involvement of more senior agency personnel and a rolling review of the NDA.
Daiichi Sankyo (OTCPK:DSKYF) (OTCPK:DSNKY) intends to reorganize its U.S. commercial operations as it transitions its maturing primary care product portfolio to specialty offerings in cardiovascular, pain management and oncology.
The reorganization will reduce expenses, mainly from the elimination of 1,000 to 1,200 jobs from the U.S. home office in Parsippany, NJ, field-based positions and others. The R&D group will be unaffected.
Under the terms of the agreement, PeptiDream will use its proprietary Peptide Discovery Platform System technology to generate certain peptides against multiple targets of interest selected by Sanofi. PeptiDream will receive an undisclosed upfront payment, research funding, preclinical and clinical milestones and royalties of commercial sales.
PeptiDream also has collaborations with Amgen (NASDAQ:AMGN), AstraZeneca (NYSE:AZN), Bristol-Myers Squibb (NYSE:BMY), Eli Lilly (NYSE:LLY), GlaxoSmithKline (NYSE:GSK), Novartis (NYSE:NVS), Mitsubishi Tanabe (OTCPK:MTZPY), Daiichi Sankyo (OTCPK:DSNKY), Merck (NYSE:MRK) and Ipsen (OTCPK:IPSEY).