publication date: Sep. 28, 2018

Drugs & Targets

FDA approves Vizimpro for NSCLC indication

FDA has approved Vizimpro (dacomitinib), a kinase inhibitor for the first-line treatment of patients with metastatic non-small cell lung cancer with epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test.

Vizimpro is sponsored by Pfizer.

The safety and efficacy of Vizimpro was demonstrated in ARCHER 1050, a randomized, multicenter, multinational, open-label study. Patients were required to have unresectable, metastatic NSCLC with no prior therapy for metastatic disease or recurrent disease with a minimum of 12 months disease-free after completion of systemic therapy; an Eastern Cooperative Oncology Group performance status of 0 or 1; EGFR exon 19 deletion or exon 21 L858R substitution mutations. A total of 452 patients were randomized 1:1 to Vizimpro (n=227) or gefitinib (n=225). The primary endpoint was progression-free survival as determined by blinded Independent Radiologic Central review, and additional efficacy outcomes included overall response rate, duration of response (DoR) and overall survival.

A statistically significant improvement in PFS as determined by the IRC was demonstrated for patients randomized to Vizimpro compared with gefitinib (HR = 0.59 [95% CI: 0.47, 0.74], p <0.0001). Median PFS in the Vizimpro group was 14.7 months (95% CI: 11.1, 16.6) compared with 9.2 months (95% CI: 9.1, 11.0) in the gefitinib arm.

“EGFR-mutated advanced non-small cell lung cancer is a common illness, especially in the Asian population, and new treatment options will ultimately benefit patients,” said Tony Mok, primary investigator for the ARCHER 1050 study and chair of Department of Clinical Oncology, The Chinese University of Hong Kong. “The findings from ARCHER 1050 suggest that Vizimpro should be considered as a new first-line treatment option for patients with EGFR-mutated non-small cell lung cancer exon 19 deletion or exon 21 L858R substitution mutations.”

Among 227 patients with EGFR-mutated metastatic NSCLC who received Vizimpro in ARCHER 1050, the most common (> 20%) adverse reactions were diarrhea (87%), rash (69%), paronychia (64%), stomatitis (45%), decreased appetite (31%), dry skin (30%), decreased weight (26%), alopecia (23%), cough (21%), and pruritus (21%). Serious adverse reactions occurred in 27 percent of patients treated with Vizimpro. The most common (≥1%) serious adverse reactions reported were diarrhea (2.2%) and interstitial lung disease (1.3%). The full prescribing information for Vizimpro can be found here.

In 2012, Pfizer and SFJ Pharmaceuticals entered into a collaborative development agreement to conduct ARCHER 1050 across multiple sites.

SFJ is a global drug development company, which provides a unique and highly customized co-development partnering model for the world’s top pharmaceutical and biotechnology companies. Under this agreement, SFJ Pharmaceuticals provided the funding and conducted the trial to generate the clinical data used to support this application.

Pfizer retains all rights to commercialize Vizimpro globally.


FDA approves Copiktra for CLL/SLL indications

FDA has approved Copiktra (duvelisib), an oral inhibitor of phosphoinositide 3-kinase and the first approved dual inhibitor of PI3K-delta and PI3K-gamma. Copiktra is approved for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma after at least two prior therapies.

The agent is sponsored by Verastem Inc.

Copiktra also received accelerated approval for the treatment of adult patients with relapsed or refractory follicular lymphoma after at least two prior systemic therapies. The indication in FL is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Use of Copiktra is associated with a boxed warning for four fatal and/or serious toxicities: infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem Oncology is implementing an informational Risk Evaluation and Mitigation Strategy to provide appropriate dosing and safety information to better support physicians in managing their patients on Copiktra.

Additionally, use of Copiktra is also associated with adverse reactions which may require dose reduction, treatment delay or discontinuation of Copiktra. Warnings and precautions are provided for infections, diarrhea or colitis, cutaneous reactions, pneumonitis, hepatotoxicity, neutropenia, and embryo-fetal toxicity.


FDA grants QIDP and Fast Track Designations to Cidara

FDA has granted Qualified Infectious Disease Product and Fast Track designations for the company’s prophylaxis development program for its lead antifungal product candidate, rezafungin for injection.

The drug is sponsored by Cidara Therapeutics Inc.

Specifically, the QIDP designation is for the development of rezafungin for the prevention of invasive fungal infections in adults undergoing allogeneic bone marrow transplantation. Cidara previously announced QIDP designation for rezafungin for the treatment of invasive fungal infections caused by Candida.

Cidara is developing rezafungin, a novel antifungal echinocandin, as a once-weekly, high-exposure therapy for the treatment and prevention of serious invasive fungal infections. Rezafungin is being studied to address unmet needs in the treatment of candidemia and invasive candidiasis as well as for prophylaxis of invasive fungal infections due to common fungal pathogens: Candida, Aspergillus and Pneumocystis.

No agent has been approved to date to prevent infections caused by these pathogens and current prophylaxis regimens often require multiple antifungal drugs with safety and tolerability issues. Cidara plans to commence the phase III ReSPECT prophylaxis clinical trial of rezafungin in patients undergoing allogeneic bone marrow transplantation in the first quarter of 2019.

The QIDP designation, provided under the Generating Antibiotic Incentives Now Act, offers certain incentives for the development of new antifungal and antibacterial drugs, including Fast Track, priority review and, if rezafungin is ultimately approved by the FDA, eligibility for an additional five years of marketing exclusivity. Fast Track designation enables more frequent interactions with the FDA review team to expedite drug development.


Blincyto approved In Japan for relapsed or refractory B-cell ALL

Japanese Ministry of Health, Labour and Welfare has granted marketing approval for Blincyto (blinatumomab) for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia. Blincyto was developed in Japan by Amgen Astellas BioPharma K.K., a joint venture between Amgen and Astellas Pharma Inc., a pharmaceutical company headquartered in Tokyo.

Blincynto is sponsored by Amgen Inc.

Blincyto is the first-and-only bispecific T cell engager immunotherapy construct approved globally. It is also the first approved immunotherapy from Amgen’s BiTE platform, an innovative approach that helps the body’s immune system target cancer cells.

The approval is based on data from multiple global studies, including the phase III TOWER study and Japan phase Ib/II Horai study. In the TOWER study, Blincyto demonstrated a superior improvement in median overall survival versus standard of care chemotherapy.

Median OS was 7.7 months (95% CI: 5.6, 9.6) for Blincyto versus 4.0 months (95 percent CI: 2.9, 5.3) for SOC (HR for death=0.71; p=0.012). Safety results among subjects who received Blincyto were comparable to those seen in the previous phase II studies of Blincyto in adult patients with Philadelphiachromosome-negative relapsed or refractory B-cell precursor ALL.

In the phase Ib/II Horai study, Blincyto was administered to 35 Japanese adult and pediatric patients with relapsed or refractory B-cell precursor ALL. The safety results from the Horai study were comparable to those seen in the global studies, including TOWER.

Blincyto is now approved in 57 countries, including the U.S., all member countries in the European Union and the European Economic Area, Canada and Australia.

The TOWER study was a phase III, randomized, active-controlled, open-label study investigating the efficacy of Blincyto versus SOC chemotherapy in 405 adult patients with Ph- relapsed or refractory B-cell precursor ALL.

The study enrolled a difficult-to-treat patient population which included patients with one or more relapses or refractory disease. In the Blincyto arm, this included 35 percent of patients that had relapsed post-allogenic hematopoietic stem cell transplant and excluded those with late first relapse (≥12 months after initial remission).

Patients were randomized in a 2:1 ratio to receive Blincyto (n=271) or treatment with investigator choice of SOC chemotherapy (n=134). The determination of efficacy was based on OS. These results were published in The New England Journal of Medicine.

The Horai study is a phase Ib/II, single-arm, open-label study evaluating the safety and efficacy of Blincyto in Japanese adult and pediatric patients with relapsed or refractory B-cell precursor ALL. The primary endpoint for the phase Ib portion was incidence of dose-limiting toxicities; the primary endpoint for the phase II portion was complete remission or complete remission with partial hematologic recovery within 12 weeks of treatment with Blincyto. Secondary endpoints include duration of response, OS and relapse-free survival. An extension of the study is ongoing.


European Commission approves Coherus’s Udenyca

The European Commission has granted marketing authorization to Udenyca (formerly CHS-1701), a pegfilgrastim (Neulasta) biosimilar. Udenyca is one of the first pegfilgrastim biosimilars to gain marketing authorization in Europe.

The drug is sponsored by Coherus BioSciences Inc.

Udenyca (pegfilgrastim-cbqv), formerly CHS-1701, is a growth-colony-stimulating-factor designed to decrease the chance of infection as manifested by febrile neutropenia (fever, often with other signs of infection, associated with an abnormally low number of infection-fighting white blood cells), in patients with non-myeloid cancer who are receiving myelosuppressive chemotherapy that has a clinically significant incidence of febrile neutropenia.

Udenyca drug substance manufacturing is located in Boulder, CO. Pegfilgrastim is one of the largest selling oncology biologics with worldwide revenues in excess of $4.5 billion in 2017. Udenyca is not yet available for commercial sale.

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