Keeping Track: FDA Celebrates Thanksgiving With Approval Cornucopia

FDA entered the holiday with approvals for two novel agents and a host of new indications.

FDA, sponsors and patients have a fair bit to be thankful for this season, with a slew of approvals including Eli Lilly & Co.'s Portrazza (necitumumab), which is the 39^th novel agent approved by the Center for Drug Evaluation and Research in 2015, and CSL Ltd.'s adjuvanted flu vaccine Fluad, the 11th novel biologic cleared by the Center for Biologics Evaluation and Research.

Lilly's Portrazza Offers New First-Line Option For Hard-To-Treat Lung Cancer Patients

FDA approved Portrazza (necitumumab), a fully human epidermal growth factor receptor inhibitor monoclonal antibody, for use in combination with cisplatin and gemcitabine for first-line treatment of metastatic squamous non-small cell lung cancer (NSCLC) on Nov. 24, 2015. The standard review agent was submitted on Dec. 2, 2014.

Lilly highlighted the medical need addressed by Portrazza, noting a five-year survival rate of less than 5% in metastatic squamous NSCLC. The squamous form of the disease is an orphan indication.

The pivotal trial, SQUIRE, is "the first and only randomized Phase III study conducted specifically in patients with metastatic squamous NSCLC to demonstrate a statistically significant improvement in overall survival over gemcitabine and cisplatin alone, specifically in the first-line setting," according to Lilly.

(The CDER Novel Approvals chart tracks new molecular entity and novel therapeutic biologic approvals for the year.)

CSL's Fluad Is First Adjuvanted Seasonal Flu Vaccine Approved

CSL's recent acquisition of Novartis AG's influenza vaccine business has paid off in with its first new approval, the influenza vaccine Fluad. It is the first seasonal flu vaccine approved with an adjuvant in the U.S. It was first approved in Italy in 1997.

Fluad is a trivalent vaccine based on three influenza virus strains (two subtype A and one type B), with the addition of the adjuvant MF59, an oil-in-water emulsion of squalene oil. "Squalene, a naturally occurring substance found in humans, animals and plants, is highly purified for the vaccine manufacturing process," FDA noted in its announcement of the accelerated approval on Fluad on Nov. 24, 2015.

Fluad is indicated for prevention of seasonal influenza in people ages 65 and older, who account for most of the mortality and hospitalization associated with the illness.

FDA approved Fluad on the basis of a 7,082-patient trial that found comparable immunogenicity to Agriflu, an unadjuvanted trivalent flu vaccine also included in the Novartis/CSL deal. Safety was evaluated in "approximately 27,000 additional individuals 65 years of age and older," FDA added.

(The CBER Novel Approvals chart tracks new biologics cleared by FDA's Center for Biologics Evaluation and Research during the year.)

Bristol Racks Up Another Breakthrough Indication For Opdivo, In Kidney Cancer

Bristol-Myers Squibb Co.'s checkpoint inhibitor immunotherapy Opdivo (nivolumab) collected yet another supplemental approval on Nov. 23, adding a breakthrough therapy-designated use for treatment of metastatic renal cell carcinoma patients whose disease worsened after treatment with an anti-angiogenic agent. The approval came fast – only one week after Bristol announced that FDA had accepted the sBLA for review.

Opdivo is the first metastatic RCC therapy to show a survival advantage since the approval of Pfizer's Torisel (temsirolimus) in 2007, FDA said.

The pivotal open-label trial randomized 821 patients to either Opdivo or Novartis' Afinitor (everolimus). Opdivo patients had an average overall survival of 25 months, compared with 19.6 months for Afinitor – an effect that "was observed regardless of the PD-L1 expression level of patients’ renal cell tumors," FDA pointed out.

"Additionally, 21.5 percent of those treated with Opdivo experienced a complete or partial shrinkage of their tumors, which lasted an average of 23 months, compared to 3.9 percent of those taking Afinitor, lasting an average of 13.7 months," FDA said.

BI's Pradaxa Adds Fourth Indication In Five Years

Boehringer Ingelheim GMBH's Pradaxa (dabigatran) was approved for a new indication on Nov. 20, extending use of the anticoagulant to prophylaxis of deep vein thrombosis and pulmonary embolism in patients undergoing hip replacement surgery. The claim is based on two Phase III studies, RE-NOVATE and RE-NOVATE II.

Pradaxa's commercialization prospects were boosted by the Oct. 16, 2015 approval of the first specific reversal agent for a new-generation anticoagulant, BI's Praxbind (idarucizumab), which reverses the anticoagulant effects of dabigatran when needed for emergency surgery or urgent procedures or in life-threatening or uncontrolled bleeding (Also see "Can Praxbind Push Pradaxa Ahead?" - Pink Sheet, 16 Oct, 2015.).

AstraZeneca Crestor Extends Pediatric Indication

FDA approved a new pediatric claim forAstraZeneca PLC's Crestor (rosuvastatin) on Nov. 20, extending use of the cholesterol-lowering drug to pediatric patients 8 to 17 years of age with heterozygous familial hypercholesterolemia (HeFH). Crestor was already indicated in patients ages 10 to 17 with HeFH, AZ noted.

In children with HeFH, Crestor is indicated to "reduce total cholesterol, LDL C (“bad cholesterol”) and ApoB if after failing an adequate trial of diet therapy the following findings are present: LDL-C > 190 mg/dL or > 160 mg/dL and there is a positive family history of premature cardiovascular disease (CVD) or two or more other CVD risk factors," AstraZeneca said.

Emergent's Anthrax Vaccine Gains Post-Exposure Prophylaxis Claim

Emergent BioSolutions Inc.'s Biothrax (anthrax vaccine, adsorbed) was cleared Nov. 23 for a new indication to prevent disease following suspected or confirmed exposure to Bacillus anthracis in people 18 through 65 years of age in conjunction with antibiotic treatment. BioThrax was initially approved by the FDA in 1970 for prevention of anthrax disease in persons at high risk of exposure.

The post-exposure prophylaxis indication was approved under FDA's animal rule, which allows animal data to be used as the basis for approval when human efficacy studies are not ethical or feasible. FDA noted that "BioThrax is the first vaccine to receive approval based on the Animal Rule."

(See the User Fee Goals chart on the FDA Performance Tracker for information on pending and recently approved applications.)