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FDA grants Priority Review to Roche’s baloxavir marboxil for the treatment of influenza

On June 26, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY), reported that the U.S. Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) and granted Priority Review for baloxavir marboxil as a single-dose, oral treatment for acute, uncomplicated influenza in patients 12 years and older (Press release, Hoffmann-La Roche, JUN 26, 2018, View Source [SID1234527464]). The FDA is expected to make a decision on approval by 24 December 2018. A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.

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"The severity of the recent flu season underscores the need for new options beyond currently available treatments, and if approved, baloxavir marboxil would be the first flu medicine with a novel proposed mechanism of action in nearly 20 years," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Baloxavir marboxil has been shown in clinical trials to decrease the duration of symptoms with one dose, and demonstrated a significant reduction in viral shedding in just one day. We look forward to working with the FDA during the review process."

Baloxavir marboxil is a first-in-class, single-dose investigational oral medicine with a novel proposed mechanism of action designed to target the flu virus, including oseltamivir-resistant strains and avian strains (H7N9, H5N1).7,8,9 Unlike other currently available antiviral treatments, baloxavir marboxil is designed to inhibit the cap-dependent endonuclease protein within the flu virus, which is essential for viral replication.10,11

The NDA is based on results from the phase III CAPSTONE-1 study of a single dose of baloxavir marboxil compared with placebo or oseltamivir 75 mg, twice daily for five days, in otherwise healthy people with flu. Additionally, results from a placebo-controlled phase II study in otherwise healthy people with the flu is included as supporting data in the NDA.

About CAPSTONE-1
CAPSTONE-1 is a phase III multicentre, randomised, double-blind, placebo-controlled study that evaluated the efficacy and safety of baloxavir marboxil in 1,436 people in the United States and Japan. The primary endpoint of the study was time to alleviation of symptoms (TTAS), and important secondary endpoints were time to resolution of fever, time to cessation of viral shedding and the proportion of participants positive for influenza virus titre, or virus levels in the body, by time point. The study found the following results:

Baloxavir marboxil met its primary and secondary endpoints compared to placebo:
Significantly reduced the duration of flu symptoms by more than one day (median time 53.7 hours versus 80.2 hours; p<0.0001);
Significantly reduced the duration of fever by nearly a day (median time 24.5 hours versus 42.0 hours; p<0.0001);
Significantly reduced the length of time viruses continued to be released from the body (median time of viral shedding; 24.0 hours versus 96.0 hours; p<0.0001);
Significantly reduced the levels of virus in the nose and throat from 24 hours through 120 hours.
Similar efficacy results were seen between baloxavir marboxil and oseltamivir in relation to duration of symptoms and fever reduction, but significant differences were observed in time to cessation of viral shedding favouring baloxavir marboxil:
No significant reduction in duration of symptoms (median time 53.5 hours versus 53.8 hours; p=0.7560);
No significant reduction in time to resolution of fever (median time 24.4 hours versus 24.0 hours; p=0.9225);
Significantly reduced the length of time the virus continued to be released from the body (viral shedding; 24.0 hours versus 72.0 hours; p<0.0001);
Significantly reduced the levels of virus in the nose and throat at 24 hours and 72 hours.
Baloxavir marboxil was well-tolerated and had a numerically lower overall incidence of adverse events (20.7%) reported compared with placebo (24.6%) or oseltamivir (24.8%). The most common adverse events reported were diarrhoea (3.0%), bronchitis (2.6%), nausea (1.3%) and sinusitis (1.1%), and all of these adverse events occurred at a lower frequency than placebo.

About baloxavir marboxil
Baloxavir marboxil is a first-in-class, single-dose investigational oral medicine with a novel proposed mechanism of action designed to target the influenza ("flu") A and B viruses, including oseltamivir-resistant strains and avian strains (H7N9, H5N1).7,8,9 Unlike other currently available antiviral treatments, baloxavir marboxil is the first in a new class of antivirals designed to inhibit the cap-dependent endonuclease protein within the flu virus, which is essential for viral replication.

Baloxavir marboxil is being studied in an ongoing phase III development program including paediatric populations with influenza. Data from the global phase III study (CAPSTONE-2) in patients 12 years and older with a high risk of complications from influenza, as defined by the Centers for Disease Control and Prevention (CDC), will be shared at a later date.

Baloxavir marboxil was discovered by Shionogi & Co., Ltd. and is being developed globally by the Roche Group (which includes Genentech in the U.S.) and Shionogi & Co., Ltd. Under the terms of this agreement, Roche holds worldwide rights to baloxavir marboxil excluding Japan and Taiwan, which will be retained exclusively by Shionogi & Co., Ltd. Baloxavir marboxil was approved in February 2018 by the Japanese Ministry of Health, Labour and Welfare for the treatment of influenza types A and B in adult and paediatric patients and is being commercialised in Japan and marketed under the brand name Xofluza.

Selective AXL inhibitor bemcentinib meets pre-specified efficacy endpoint in stage 1 of NSCLC phase II combination trial with KEYTRUDA®

On June 26, 2018 BerGenBio ASA (OSE:BGBIO) reported that on a top-line, preliminary basis, the first efficacy endpoint has been met in its Phase II clinical trial (BGBC008) evaluating bemcentinib, a first-in-class oral selective AXL inhibitor, in combination with the Merck & Co., Inc., Kenilworth, N.J., USA anti-PD-1 therapy KEYTRUDA (pembrolizumab) as a potential new treatment regimen for advanced non-small cell lung cancer (NSCLC)(Press release, BerGenBio, JUN 26, 2018, View Source [SID1234527463]) . The primary efficacy endpoint requires at least four patients (out of the first 22 treated patients) to achieve clinical responses when treated with the novel drug combination, defined as either complete or partial response, as measured by Response Evaluation Criteria in Solid Tumors (RECIST).

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "Immunotherapy has become a major component of the treatment of many cancers – patients who respond to immune checkpoint inhibitors like KEYTRUDA enjoy long-term disease control with excellent quality of life. Unfortunately, only a minority of lung cancer patients receiving KEYTRUDA monotherapy in second-line respond to treatment. The BGBC008 combination trial of bemcentinib with KEYTRUDA evaluates whether the addition of our selective AXL inhibitor will improve the outcome of immunotherapy.

"Clearing the first efficacy threshold in this ongoing Phase II trial is very encouraging and we intend to begin enrolment for Stage 2 of this study in which 24 further patients will be enrolled under the same protocol. Thus far, we are delighted to see activity in a number of patients receiving this novel treatment regimen. A particularly encouraging finding is that we see responses in patients who are negative for the PD-L1 biomarker, for whom KEYTRUDA monotherapy is not indicated. The second stage of the trial is intended to confirm activity and biomarker correlation in a larger group of patients – comprehensive analysis of the Phase II data will continue and will be presented at a future scientific conference.

"Successfully completing this important milestone further supports our belief in the potential of bemcentinib to become a cornerstone of cancer therapy. We look forward to sharing more details from our Phase II clinical programme during major clinical conferences in the coming months."

About the BGBC008 trial combining bemcentinib with KEYTRUDA (pembrolizumab) conducted in collaboration with Merck & Co., Inc.
Design
The BGBC008 trial is a Phase II multi-centre open-label study of bemcentinib in combination with KEYTRUDA (pembrolizumab) in previously treated, immunotherapy naïve, patients with advanced adenocarcinoma of the lung, the most common form of non-small cell lung cancer (NSCLC). The objective of the trial is to determine the anti-tumour activity of this novel drug combination and responses will be correlated with biomarker status (including AXL kinase and PD-L1 expression).

A pre-defined efficacy endpoint was set at four or more responses observed in the first 22 patients based on previously reported response rates to KEYTRUDA monotherapy in the second line setting in NSCLC.

Status June 2018
To date, 4 responses (partial responses as per RECIST v1.1) have been observed in the first 22 patients. A number of patients remain ongoing and are awaiting the confirmation of their best response.

Patients generally tolerated the novel drug combination well – no new safety events were reported from the combination of bemcentinib with KEYTRUDA at full dose.

A preliminary interim analysis of the trial (from 15 patients evaluable for response) was presented at ASCO (Free ASCO Whitepaper) 2018, where tumour shrinkage was observed in about half of the patients analysed to date. Results looked particularly promising in patients who did not express the PD-L1 biomarker, i.e. representing 1/3 of NSCLC patients, a group for whom KEYTRUDA monotherapy as a second line is not indicated.

For more information please access trial NCT03184571 at www.clinicaltrials.gov.

Nordic Nanovector Appoints Eduardo Bravo as Chief Executive Officer

On June 25, 2018 Nordic Nanovector ASA (OSE: NANO) reported that Eduardo Bravo has been appointed as its Chief Executive Officer (Press release, Nordic Nanovector, JUN 25, 2018, View Source [SID1234553497]).

Mr Bravo brings more than 25 years’ experience in the biopharmaceutical industry and a strong track record in leading and growing international biotech and pharmaceutical organisations. Since 2011, as CEO of TiGenix, a dual-listed (Euronext Brussels and NASDAQ) biopharmaceutical company developing novel stem cell therapies, he successfully developed the company through several financing rounds, led its IPO on NASDAQ, and secured European marketing approval of its lead asset. In January 2018, Takeda Pharmaceutical Co. Ltd announced it was acquiring TiGenix for €520 million.

Prior to joining TiGenix’ predecessor, Cellerix, in 2005, Mr Bravo held several senior management positions at Sanofi-Aventis and SmithKline Beecham. He is currently Chairman of Vivet Therapeutics. He holds a degree in Business Administration and an MBA (INSEAD).

Mr Bravo will take up the CEO position in Nordic Nanovector on 2 July and will be based in London, UK.

Ludvik Sandnes, Chairman of Nordic Nanovector’s Board of Directors, said: "I am very pleased that we have attracted someone of Eduardo’s calibre to become the CEO of Nordic Nanovector. He has extensive experience in corporate and product development, which is central to Nordic Nanovector’s future success, and will provide excellent leadership under which the Company can continue to realise its significant potential with Betalutin. I would also like to thank Tone Kvåle for supporting the company as Interim CEO over the past few months."

Eduardo Bravo added: "I am looking forward to this exciting new role as the CEO of Nordic Nanovector. It is clear that the Company has an exciting future based on the significant potential of Betalutin in follicular lymphoma and NHL more broadly. I am joining an excellent board and management team and am confident that with my complementary experience and networks, we can succeed with Betalutin to provide physicians with another treatment option to improve the lives of patients who are in dire need of effective therapies to control their disease and build significant value in the company."

On joining Nordic Nanovector, Mr Bravo will be granted 250,000 PSUs (performance share units) and the company’s Board of Directors has undertaken to grant him a further 50,000 PSUs as part of the company’s annual grant of PSUs in the first quarter of 2019. For further information about the PSUs and the related warrants, see pages 66-68 in the company’s annual report for 2017. In addition, on joining Nordic Nanovector, Mr Bravo will receive a sign-on bonus of EUR 50,000 and has undertaken to invest, at minimum, the net amount after tax in Nordic Nanovector shares and will do so following this announcement.

Stemline Therapeutics Announces Completion of Rolling BLA Submission for ELZONRIS™ (tagraxofusp; SL-401) for the Treatment of BPDCN

On June 25, 2018 Stemline Therapeutics, Inc. (Nasdaq:STML), a clinical-stage biopharmaceutical company developing novel oncology therapeutics, reported that it has completed submission of a rolling Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for ELZONRISTM (tagraxofusp; SL-401), a potential treatment for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), a CD123+ malignancy of unmet medical need for which the agent was awarded Breakthrough Therapy Designation (BTD) (Press release, Stemline Therapeutics, JUN 25, 2018, View Source [SID1234532234]).

Survival probability in first-line BPDCN patients who received ELZONRIS (12mcg/kg/day) in Stages 1, 2 and 3

Ivan Bergstein, M.D., Stemline’s CEO, commented, "The completion of our rolling BLA submission is a major milestone for Stemline and the overall BPDCN patient community. We want to recognize the hard work of our dedicated investigators as well as the entire Stemline team in completing this submission. We also want to especially thank all of the patients and their families who participated in the clinical development program. We are committed to bringing this promising agent to BPDCN patients as rapidly as possible."

BPDCN Efficacy – Stages 1, 2, and 3, ELZONRIS (12mcg/kg/day) (n=42)
The trial of investigational agent, ELZONRIS, in patients with BPDCN was comprised of 3 stages, with Stage 3 serving as the pivotal cohort for confirmation of efficacy. To ensure ongoing access to ELZONRIS, patients with BPDCN are being enrolled in an additional cohort, Stage 4. Stage 3 met its primary endpoint with a CR+CRc (complete response + clinical complete response) rate of 54% (95% CI: 25.1, 80.8). A summary of efficacy results is shown below.

Summary table: Efficacy of ELZONRIS (12mcg/kg/day) in patients with BPDCN (Stages 1, 2 and 3 [n=42])

Line of Therapy First-line Relapsed / Refractory
n 29 13
ORR, n (%) 26 (90%) 9 (69%)
CR+CRc+CRi, n (%) 21 (72%) 5 (38%)
CR 12 1
CRc 7 3
CRi 2 1
PR, n (%) 5 (17%) 4 (31%)
Bridged to SCT, n (%) 13 (45%) 1 (8%)
Abbreviations: ORR=overall response rate; CR=complete response; CRc=clinical CR (CR with minimal residual skin abnormality); CRi=CR with incomplete hematologic recovery; PR=partial response; SCT=stem cell transplant.

Overall Safety
148 patients received ELZONRIS (12mcg/kg/day) across all Stemline-sponsored trials, including in BPDCN, myeloproliferative neoplasms, and acute myeloid leukemia. A summary of safety results is shown below.

Summary table: Safety and tolerability of ELZONRIS (12mcg/kg/day) in all Stemline-sponsored clinical trials (n=148)

Most Common Adverse Events (AEs) (>15% treatment-related AEs, TRAEs)
Preferred Term All Grades, n (%) TRAEs, n (%)
TRAEs All AEs Gr 1-2 Gr 3 Gr 4 Gr 5
ALT increased 65 (43.9%) 80 (54.1%) 31 (20.9%) 34 (23.0%) 0 (0.0%) 0 (0.0%)
AST increased 65 (43.9%) 74 (50.0%) 30 (20.3%) 31 (20.9%) 4 (2.7%) 0 (0.0%)
Hypoalbuminaemia 65 (43.9%) 73 (49.3%) 64 (43.2%) 1 (0.7%) 0 (0.0%) 0 (0.0%)
Thrombocytopenia 39 (26.4%) 48 (32.4%) 7 (4.7%) 8 (5.4%) 24 (16.2%) 0 (0.0%)
Nausea 38 (25.7%) 70 (47.3%) 37 (25.0%) 1 (0.7%) 0 (0.0%) 0 (0.0%)
Pyrexia 33 (22.3%) 60 (40.5%) 33 (22.3%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Fatigue 30 (20.3%) 67 (45.3%) 26 (17.6%) 4 (2.7%) 0 (0.0%) 0 (0.0%)
Weight increased 28 (18.9%) 42 (28.4%) 28 (18.9%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Chills 26 (17.6%) 40 (27.0%) 25 (16.9%) 1 (0.7%) 0 (0.0%) 0 (0.0%)
Capillary leak syndrome (CLS)a 25 (16.9%) 25 (16.9%) 16 (10.8%) 5 (3.4%) 3 (2.0%) 1 (0.7%)
Hypotension 23 (15.5%) 36 (24.3%) 17 (11.5%) 5 (3.4%) 1 (0.7%) 0 (0.0%)
Oedema peripheral 22 (14.9%) 57 (38.5%) 21 (14.2%) 1 (0.7%) 0 (0.0%) 0 (0.0%)
a0.7% (1/148) for all trials (12mcg/kg/day) and 1.6% (3/182) for all trials (all doses) were grade 5. A myocardial infarction, grade 5, was also reported in a patient who experienced a grade 4 CLS.

Overall Survival (OS)
In first-line BPDCN patients who received ELZONRIS (12mcg/kg/day) in Stages 1, 2 and 3, the median OS has not been reached. Median follow up was 13.8 months (range: 0.2-37.4+ months).

About ELZONRISTM (tagraxofusp; SL-401)
ELZONRISTM (tagraxofusp; SL-401) is a novel targeted investigational therapy directed to CD123, a cell surface receptor expressed on a range of malignancies. ELZONRIS has successfully completed a pivotal trial in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an indication for which it was granted Breakthrough Therapy Designation (BTD). A rolling Biologics License Application (BLA) submission has been completed. ELZONRIS is also being evaluated in clinical trials in additional indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), acute myeloid leukemia (AML), and myeloma.

Andarix Pharmaceuticals to Present at the Metals to Medicine Gordon Research Conference

On June 25, 2018 Andarix Pharmaceuticals, a clinical stage company aimed at developing a targeted peptide therapies for hard to treat cancers, reported that it will present a poster at the Metals in Medicine Gordon Research Conference (Press release, Andarix Pharmaceuticals, JUN 25 2018, View Source [SID1234527792]) .The conference will take place June 25-29 in Andover, NH.

The theme of the conference is: The Indispensable Role of Metals in Medical Diagnostics, Therapeutics and Beyond. Andarix will be presenting clinical findings pertaining to Tozaride, a Rhenium metal-based drug developed by the company. The conference is an opportunity for Andarix to present its innovative technology to world
leading scientists and international metal-science experts.

About Tozaride
Tozaride is a novel, best-in-class therapeutic for lung and other cancers, which is based on a radio-labeled somatostatin peptide. Early clinical studies demonstrated that Tozaride is well tolerated and that treatment can promote disease stabilization and improve overall survival in heavily pre-treated advanced lung cancer patients. Tozaride targeted radiotherapy represents a new treatment paradigm which is expected to yield
significant clinical benefits for both small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC) patients. This therapeutic stands to provide an additional treatment option for patients who are not eligible for, or who have not responded to current therapies.