The Sandoz unit of Novartis AG (NYSE:NVS; SIX:NOVN) said FDA approved a BLA for Erelzi etanercept-szzs (GP2015), a biosimilar of Enbrel etanercept from Amgen Inc. (NASDAQ:AMGN). Erelzi is approved in all indications included on Enbrel's label. Novartis spokesperson Eric Althoff said "it is too early to speculate" about launch timing or a price for the biosimilar.
In February, Amgen filed suit against Sandoz, claiming the biosimilar infringes on five Enbrel patents. According to lawsuit-related documents filed this month, both parties have agreed to a preliminary injunction barring Sandoz from selling Erelzi and a trial has been scheduled for April 17, 2018 (see BioCentury Extra, Feb. 29).
In a statement, Amgen said it is confident in its Enbrel patents. FDA first approved Enbrel in 1998, and the company's Enbrel patents expire in 2029. It reported $5.4 billion in Enbrel sales in 2015 (see BioCentury, July 25).
FDA spokesperson Theresa Eisenman told BioCentury via email that Erelzi's label "will look similar to the reference product label." Althoff said it would "include a full package of analytical, nonclinical and clinical data confirming similarity to the licensed product." Erelzi's naming uses FDA's four-letter suffix system to distinguish between non-interchangeable biologics.
FDA announced the approval after market close. Novartis shed $0.30 to $79.34 on Tuesday, and Amgen lost $0.75 to $170.76.
Ariad Pharmaceuticals Inc. (NASDAQ:ARIA) completed submission of a rolling NDA to FDA for brigatinib (AP26113) to treat anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in patients whose tumors are resistant to Xalkori crizotinib. The company is seeking accelerated approval and requested Priority Review of the dual inhibitor of ALK and EGFR, which has breakthrough therapy designation.
The NDA is based on data from the open-label, international, pivotal Phase II ALTA trial. Brigatinib produced a 46-54% objective response rate (ORR) in the study, according to an abstract released in May ahead of the American Society of Clinical Oncology (ASCO) meeting. At the June meeting, Ariad said brigatinib led to a median progression-free survival (PFS) of 9.2-12.9 months and a one-year overall survival rate of 71-80% (see BioCentury Extra, May 18).
Ariad gained $0.22 to $10.43 on Tuesday.
FDA accepted for review a BLA from CSL Ltd. (ASX:CSL) for CSL830 (subcutaneous C1-INH) to prevent hereditary angioedema (HAE) attacks. The therapy is a low-volume, subcutaneous complement 1 (C1) esterase inhibitor. CSL markets an IV version of a C1 esterase inhibitor called Berinert to treat HAE.
Mitsubishi Tanabe Pharma Corp. (Tokyo:4508) said FDA accepted an NDA for edaravone (MCI-186) to treat amyotrophic lateral sclerosis (ALS). Its PDUFA date is June 16, 2017.
Edaravone is an IV cerebral neuroprotectant and free radical scavenger. It is approved in Japan as Radicut to treat ALS and stroke, and in South Korea for ALS.
Rigel Pharmaceuticals Inc. (NASDAQ:RIGL) surged $1.29 (49%) to $3.93 on Tuesday after its fostamatinib disodium (formerly R788) met the primary endpoint of stable platelet response in a double-blind, 76-patient Phase III study to treat chronic/persistent idiopathic thrombocytopenic purpura (ITP). The company plans to submit an NDA to FDA for the oral spleen tyrosine kinase (SYK) inhibitor by the end of 1Q17.
A significantly greater proportion of patients receiving 100 mg twice-daily fostamatinib achieved a stable platelet response by week 24 compared with placebo (18% vs. 0%, p=0.0261). A stable response was defined as platelet counts of at least 50,000/uL of blood for at least four of the final six qualifying blood draws.
The most frequent adverse events were gastrointestinal-related, and Rigel said fostamatinib's safety profile was "consistent with prior clinical experience."
Rigel expects data from a second identical Phase III study of fostamatinib in October or November, along with an interim update from an open-label extension study.
The Phase III trials include patients who received at least one prior ITP treatment, such as steroids, Rituxan rituximab, a splenectomy or a thrombopoietin (TPO) mimetic.
Portola Pharmaceuticals Inc. (NASDAQ:PTLA) reported interim data from the single-arm, open-label Phase IIIb/IV ANNEXA-4 study of AndexXa andexanet alfa showing 79% of patients achieved excellent or good hemostasis within 12 hours of infusion with the anticoagulant reversal agent. The company said the ongoing open-label study is "on track" to meet its co-primary efficiency endpoints, which are percent change in anti-Factor Xa activity at two hours and hemostasis at 12 hours after infusion.
ANNEXA-4 is evaluating AndexXa in patients who present with an acute major bleed while receiving a Factor Xa inhibitor. Patients receive a bolus dose of AndexXa over 30 minutes followed by a two-hour infusion.
Besides the interim efficacy data, Portola also reported safety data from the study. There were thrombotic events in 12 patients within 30 days of receiving of AndexXa, with 10 patient deaths. Portola said the events "occurred within the range expected" in the patient population.
The interim safety analysis was based on 67 patients, and the interim efficacy analysis was based on 47 patients. ANNEXA-4 has enrolled more than 130 of a planned 270 patients.
The interim results were published Tuesday in The New England Journal of Medicine and were presented at the European Society of Cardiology meeting.
AndexXa is a modified human Factor Xa protein that acts as a decoy to target and sequester Factor Xa inhibitors. FDA issued a complete response letter for AndexXa earlier this month. Portola said most of the letter related to manufacturing concerns (see BioCentury Extra, Aug. 18).
Portola gained $0.21 to $20.59 on Tuesday.
Vectura Group plc (LSE:VEC) said Flutiform fluticasone/formoterol missed the primary endpoint in a Phase III study to treat chronic obstructive pulmonary disease (COPD), and said partner Mundipharma International Ltd. (Cambridge, U.K.) will no longer pursue EU approval for Flutiform in the indication.
Flutiform was not superior to formoterol monotherapy on annualized rates of moderate and severe COPD exacerbations. The study enrolled 1,767 COPD patients.
Vectura declined to disclose details. Mundipharma, which conducted the study, did not respond to inquires.
Flutiform is approved in the EU and Japan to treat asthma. It is a fixed-dose combination of formoterol, a long-acting adrenergic receptor beta 2 agonist (LABA), and fluticasone, an inhaled corticosteroid, delivered via a hydrofluoroalkane metered-dose inhaler (HFA-DMI).
Mundipharma has rights to Flutiform outside North America and Japan. Kyorin Pharmaceutical Co. Ltd (Tokyo:4569) has Japanese rights.
Vectura gained Flutiform through its L441.3 million ($632.2 million) acquisition of SkyePharma plc this year (see BioCentury Extra, March 16).
Vectura lost 5.40p to 132.10p on Tuesday.
Kamada Ltd. (Tel Aviv:KMDA; NASDAQ:KMDA) advanced $0.36 to $4.89 on NASDAQ on Tuesday after its inhaled alpha-1 antitrypsin (AAT; A1AT; SERPINA1) met the primary endpoint in a 36-patient U.S. Phase II study to treat AAT deficiency (AATD). Patients who received 80 or 160 mg of the product twice daily for 12 weeks had a significant increase in the concentration of antigenic AAT in epithelial lining fluid vs. placebo (p<0.0005 for low-dose inhaled AAT and p<0.002 for high-dose).
Additionally, Kamada said both doses led to a significant increase vs. placebo in levels of anti-neutrophil elastase inhibitory levels (ANEC) in epithelial lining fluid.
AAT inhibits neutrophil elastase (ELANE; NE; HLE), and damage to lung tissue in AATD patients results from having insufficient AAT to prevent neutrophil elastase from breaking down proteins in the tissue.
Kamada plans to use the Phase II data to design a pivotal U.S. study of its inhaled AAT, and to support its responses to EMA's 120-day comments for an MAA for the therapy that the agency accepted earlier this year.
The MAA is based on a 168-patient European Phase II/III study that missed the primary endpoint of improving time to first exacerbation at one year vs. placebo. The company said lung function parameters in the study showed a significant treatment effect in the reduction of the inflammatory injury to the lung (see BioCentury Extra, May 16, 2014).
Lung-affected AATD patients have said they want new formulations of augmentation therapy -- weekly IV administration of AAT purified from human serum -- that could be self-administered or that would reduce the frequency of visits to hospitals or clinics, or home visits by nurses for infusions (see BioCentury, Oct. 12, 2015).
Kamada already markets Glassia, an IV formulation of AAT. Its inhaled formulation uses the eFlow Nebulizer System from Pari GmbH (Starnberg, Germany).
Data presented at the European Society of Cardiology meeting in Rome showed that a single intravenous administration of ischemic-tolerant mesenchymal stem cells (itMSCs) from CardioCell LLC met the primary safety endpoint and several secondary efficacy endpoints in a single-blind Phase IIa trial to treat chronic heart failure (CHF) in patients with non-ischemic cardiomyopathy.
CardioCell CEO Sergey Sikora told BioCentury that IV itMSCs met the primary endpoint of the study by showing no differences versus placebo on multiple safety measures including all-cause mortality and all-cause hospitalizations. "The patient population in this trial consisted of stable, NYHA Class 2 and 3 CHF patients. Thus, few-to-no major events were expected in both groups," Sikora said. The trial enrolled 22 patients who were evaluated at baseline and 90 days after treatment.
Patients who received IV itMSCs led to significant improvements from baseline to 90 days post-treatment compared with placebo on the six-minute walk test (p=0.02) and the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary scores (p=0.02), both secondary endpoints. The treatment missed a third secondary endpoint of improving KCCQ functional status scores vs. placebo (p=0.06).
The clinical summary score assesses symptoms and physical limitations of heart failure and includes the functional status score, along with symptoms and quality of life.
Sikora said the company expects to advance the candidate to a new clinical study by 2Q17, but did not disclose details on study design.
CardioCell is a subsidiary of Stemedica Cell Technologies Inc. (San Diego, Calif.).
Cancer company CBT Pharmaceuticals Inc. (Santa Clara, Calif.) raised $9.8 million in a series A round led by OrbiMed Asia. CBT's parent company is CRO Crown Bioscience International Inc. (TPex-E:6554), which seeded the biotech with $5 million earlier this year.
Early next year, CBT expects to begin a U.S. Phase I study of CBT-101 to treat c-Met receptor tyrosine kinase (c-MET, MET, HGFR, c-Met proto-oncogene) dysregulated cancers. The c-MET inhibitor is in a Phase I trial in China.
Also in 2017, CBT expects to start an Asian Phase I trial of CBT-501, an anti PD-1 mAb. The company has two investigational candidates: a multi-kinase inhibitor and a PD-L1 antibody.
CBT's board includes Crown Executive Chairman Guo-Liang Yu and OrbiMed Asia's Jonathan Wang.
FDA added two research areas to its Broad Agency Announcement, a method for soliciting competitive bids for research from the private sector. The agency said it now will solicit research on preventing opioid abuse through packaging, storage, delivery and disposal systems with abuse deterrent properties. It said it would use the information to determine guiding principles for industry in developing abuse deterrent opioids.
The agency also will seek out research on innovative clinical trial designs for antibacterial treatments, including strategies to increase trial enrollment.
The Blue Ribbon Panel convened to provide advice about the Obama administration's Cancer Moonshot Initiative has finalized its report, according to National Cancer Institute staff. The report, with recommendations on scientific goals of the Cancer Moonshot, will be presented to the National Cancer Advisory Board (NCAB) and made public on Sept. 7. Following approval by the NCAB, the report will be formally transmitted to the Cancer Moonshot Task Force and Vice President Joe Biden.
The report was written by members of seven working groups that developed recommendations related to clinical trials; enhanced data sharing; cancer immunology; implementation science; pediatric cancer; precision prevention and early detection; and tumor evolution and progression.
China FDA said it authorized the Prince of Wales Hospital and Queen Mary Hospital in Hong Kong as clinical trial centers, allowing registrational studies conducted at the sites to support CFDA approval. Both domestic and multinational companies will have access to the clinical trial centers.