Merck & Co. Inc. (NYSE:MRK) said late Monday FDA approved Keytruda pembrolizumab as a first-line treatment for metastatic non-small lung cancer patients with ≥50% PD-L1 expression and with no EGFR or anaplastic lymphoma kinase (ALK) tumor aberrations. The approval is the first for a mAb against PD-1 in first-line metastatic NSCLC.
FDA based the first-line approval on data from the Phase III KEYNOTE-024 trial (see BioCentury Extra, June 16).
Merck also said FDA further expanded Keytruda's label, granting the drug full approval in a second-line NSCLC setting in patients with ≥1% PD-L1 expression, following progression on or after platinum-containing chemotherapy. Keytruda had accelerated approval as a second-line NSCLC therapy, and subsequently showed a survival benefit in the KEYNOTE-010 study (see BioCentury Extra, Oct. 26, 2015).
Keytruda is also approved to treat melanoma, and has accelerated approval for head and neck cancer.
Merck & Co. Inc. (NYSE:MRK) said FDA approved Zinplava bezlotoxumab to reduce the recurrence of Clostridium difficile infection in high-risk adult patients receiving antibacterial drugs. Merck plans to launch the drug next quarter. The company did not respond to inquiries about its price.
Zinplava is a human mAb targeting C. difficile toxin B (TcdB). In June, FDA's Antimicrobial Drugs Advisory Committee voted 10-5, with one abstention, that Zinplava was safe and effective to prevent C. difficile recurrence. FDA extended its review of the drug by three months to obtain additional data and analyses from two Phase III studies of Zinplava (see BioCentury Extra, July 21).
Merck obtained exclusive, worldwide rights to Zinplava in 2009 from Medarex Inc. and the Massachusetts Biologic Laboratories (MBL) of the University of Massachusetts Medical School. Bristol-Myers Squibb Co. (NYSE:BMY) acquired Medarex later in 2009.
Global Blood Therapeutics Inc. (NASDAQ:GBT) gained $2.50 (14%) to $20.25 in early after-hours trading Monday after it said it reached agreement with FDA concerning the design of the Phase III HOPE trial of GBT440 to treat sickle cell disease patients with at least one episode of vaso-occlusive crisis in the previous year.
The study's first part will evaluate 900 and 1,500 mg GBT440 in about 150 patients, and the second part will evaluate GBT440 in 250 patients at a dose based on results from the trial's first part. The placebo-controlled trial's primary endpoint is the proportion of patients with a greater than 1 g/dL increase in hemoglobin at 24 weeks compared to baseline. Global Blood plans to start the trial by December, and expects top-line data in 1H19.
Global Blood previously reported 90-day data showing that GBT440 led to durable reductions in hemolysis in its ongoing dose-escalation Phase I/II study. The candidate has Fast Track and Orphan Drug designations to treat sickle cell disease (see BioCentury, June 10).
The company is also evaluating the allosteric modifier of hemoglobin oxygen affinity in a Phase IIa study to treat adolescents with sickle cell disease and a Phase IIa study to treat idiopathic pulmonary fibrosis (IPF).
Global Blood dipped $1.10 to $17.75 on Monday. It announced the news after market close.
Aduro Biotech Inc. (NASDAQ:ADRO) slipped $0.55 to $11.70 on Monday after it said FDA placed a partial clinical hold on trials evaluating candidates developed using the company's Listeria monocytogenes-based immunotherapy construct (LADD) platform. The hold will pause new patient enrollment in the studies, while patients already treated with LADD-based products will continue to receive treatment.
Aduro said FDA placed the hold after a blood culture sample from a pancreatic cancer patient in its Phase IIb ECLIPSE trial of CRS-207 tested positive for Listeria several months after treatment. CRS-207 is a live-attenuated strain of Listeria that expresses human mesothelin. The company said the patient was given antibiotics and that further blood cultures tested negative for Listeria. Aduro intends to propose revised study protocols to FDA this week.
In November 2015, Aduro disclosed that another pancreatic cancer patient treated with CRS-207 and GVAX Pancreas cancer vaccine developed listeriosis in a Phase IIa trial. At the time, the company said the infection was likely attributable to a protocol violation and that all of its clinical trials would continue as planned (see BioCentury Extra, Nov. 25, 2015).
CRS-207 is also in a Phase Ib trial to treat mesothelioma and a Phase I/II trial in ovarian cancer.
In addition to CRS-207, Aduro's LADD-based candidates include ADU-623, ADU-214 and ADU-741. All three are in Phase I studies to treat various cancers.
Inovio Pharmaceuticals Inc. (NASDAQ:INO) fell $1.37 (16%) to $6.99 on Monday after it said FDA placed a clinical hold on the company's planned Phase III study of VGX-3100 to treat cervical intraepithelial neoplasia (CIN) associated with HPV types 16 or 18. Inovio now expects the study to begin in 1H17. It had hoped to start it by YE16.
The company said FDA requested additional data concerning the shelf life of its redesigned Cellectra electroporation device, which is associated with the candidate's administration. Inovio said it believes the relevant data will be available this year.
In 2014, Inovio said VGX-3100 followed by electroporation with Cellectra met the primary endpoint in a Phase II trial to treat CIN associated with HPV types 16 or 18 (see BioCentury, July 23, 2014).
VGX-3100 is a DNA-based therapeutic vaccine targeting the E6 and E7 proteins of HPV 16 and 18.
Suzhou Alphamab Co. Ltd. (Suzhou, China) started a Chinese Phase I study of KN015, a long-acting human follicle stimulating hormone (FSH), to treat infertility. Compared with approved FSH treatments, which require multiple injections during a treatment cycle, KN015 could require only one subcutaneous injection, the company said. The candidate is Alphamab's first to enter the clinic.
Alphamab also hired Mike Liu as EVP of global business development. He was head of global business development at Jiangsu Hengrui Medicine Co. Ltd. (Shanghai:600276).
In its final report, the U.K.'s Accelerated Access Review recommended the creation of an Accelerated Access Pathway that would speed patient access to highly innovative products by up to four years. As part of the new pathway, five to 10 therapies or technologies each year would receive a "transformative designation" based on preclinical and early clinical data that suggest a significant benefit in either outcomes or cost.
The pathway is meant to work in parallel with other regulatory mechanisms, such as EMA's PRIME scheme, that accelerate development of certain drugs. A compound with transformative designation also would receive advice from regulators on market access and commercial arrangements. The report proposed that drug sponsors and NHS research bodies act in concert to gather clinical and real-world data to help assess drugs' value.
NICE appraisals for compounds in the pathway would be conducted in parallel with regulatory decisions, allowing for earlier reimbursement. NICE would also use managed access agreements -- as it already does in the Cancer Drugs Fund -- for products with a transformative designation so that additional data can be collected when the benefit-risk profile is uncertain.
The report called for NHS England to establish a strategic commercial unit that would allow companies to opt to enter more flexible pricing models, such as price-volume agreements, annuity-based pricing and outcome-based payments. New pricing models could be applied initially to therapies with the transformative designation, but eventually be used for a broader group of therapies.
The pathway would be managed by leaders from the National Institute for Health Research (NIHR), Medicines & Healthcare products Regulatory Agency, NICE, NHS England, NHS Improvement -- which provides support and oversight to foundation trusts and NHS trusts -- and the Department of Health. The review said patients should be involved in the selection of medicines and technologies for the pathway, and should remain involved throughout the process.
In addition, the report said the government should provide L20-L30 million ($24.5-$36.7 million) over five years to pay for drugs provided by smaller companies or not-for-profit organizations under the Early Access to Medicines Scheme (EAMS). Currently, companies providing unapproved drugs to patients under the scheme must do so free of charge.
The report also recommended NICE review its appraisal process and methods, in particular to support NHS England's ability to enact new flexible pricing schemes. The review also urged NICE to emphasize medical devices, diagnostics and precision medicine tools that would improve NHS's efficiency, and said NICE and NHS England should disinvest in outdated products and services.
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