Expedited FDA approval plays dominant role in drug approvals

FDA approvals for generic drugs outpaced new drugs in 2016, according to speakers at the AMCP Managed Care & Specialty Pharmacy Annual Meeting, in Denver, during the March 28 session, “Traditional Brand and Generic Drugs in Development.”

Last year saw “the highest number of generic drug approvals in the history of the FDA’s generic drug program,” reported Doris J. Kao, PharmD, BCPS, FCSHP, supervisor of Kaiser Permanente’s Drug Information Services in Oakland, California, and Anne Tran-Pugh, PharmD, coordinator of Kaiser Permanente’s National Medicare Formulary in Downey, California.

The FDA’s Office of Generic Drugs approved 630 abbreviated new drug applications and tentatively approved another 183, Kao reported.

Among first-time generic launches in 2016 were generic versions of Gleevec (imatinib), Glumetza (metformin ER tablet), Enablex (darifenacin), Tamiflu (oseltamivir), Nuvigil (armodafinil), Seroquel XR (quetiapine ER tablet), and Crestor (rosuvastatin). First-time generic launches scheduled for 2017 include Viagra (sildenafil) and Norvir (ritonavir 100 mg tablet).

Novel drugs did not fare as well as generics approvals. New molecular entity (NME) and new biologic license application (BLA) filings have been relatively flat since 2011, with 22 of 41 NME or BLA filings approved.

Notably, 86% of new products approved by the FDA in 2016 have not yet been approved in other countries, Kao said.

Expedited FDA approval program plays dominant role

Expedited FDA approval programs played a dominant role in new-drug approvals.

“Seventy three percent of novel new drugs had at least one method of expedited approval,” Kao said.

• 36% were fast-tracked as drugs that fill an unmet medical need for serious conditions;

• 27% were granted accelerated approval as drugs for serious conditions filling unmet need based on surrogate trial endpoints; and

• 32% were designated breakthrough therapies.

• Fully 68% were granted priority review status as drugs that offer significant improvements over existing therapies, a designation that requires FDA action within six months.

New brand drugs approved in 2016 included anti-infectives like PaxVax’s Vaxchora (cholera live vaccine), Merck Sharp & Dohme’s ZInplava (bezlotoxumab, for Clostridium difficile infection), Protein Sciences Corporation’s recombinant influenza vaccine Flublok Quadrivalent, and two influenza vaccines by Seqirus: the cell-culture Flucelvax Quadrivalent influenza vaccine and the egg-based influenza vaccine Afluria Quadrivalent.

A new GSK shingles vaccine, Shingrix, is up for FDA approval in late 2017.

Next: Pipeline 2017

Pipeline 2017

New antibiotics expected to see FDA approval this year include Melinta’s Baxdela (delafloxacin) for gram-positive and gram-negative bacterial infections and Cempra’s Taksta (sodium fusidate) for gram-positive bacterial infections.

Several central nervous system medications are expected to see FDA approval in 2017, including GW Pharmaceuticals’ Epidiolex, a marijuana-derived cannabidiol for Dravet syndrome and Lennox-Gastaut syndrome, rare pediatric epilepsy disorders, and Neurocrine Biosciences/Mitsubishi Tanabe Pharma’s Ingrezza (valbenazine) to control tardive dyskinesia (involuntary movements sometimes associated with some antipsychotic medications).

Given the country’s very high diabetes rates, surprisingly few diabetes medications are in the drugs pipeline, the speakers noted. More than 29 million Americans (9.3% of the U.S. population) have diabetes.

“You’d think there would be tons of new diabetes drugs, a lot of novel ideas-but in reality, the things coming through the pipeline are really just improvements on what’s already out there, like changes in dosing,” Tran-Pugh said. “There are a couple of contributors to that. The available drugs we have now do work pretty well. Obviously, the high cost of developing drugs and the high bar for approval of diabetes medications are also factors.”                                                              

R&D trend overview

The R&D trend now is to look for “very, very novel” ideas, she said. For example, researchers are investigating drugs that can emulate the neuroendocrine effects of gastric bypass surgery without surgery, she noted.

Tran-Pugh spotlighted three new brands approved by the FDA in 2016, all for type 2 diabetes (T2DM) management: Adlyxin (lixisenatide), Soliqua 100/33 (insulin glargine 100 units/mL / lixisenatide 33 mg/mL), and Xultophy 100/3.6 (insulin degludec 100 units/mL / liraglutide 3.6 mg/mL).

Adlyxin and Soliqua are prefilled pens for subcutaneous injection, used with diet and exercise to improve glycemic control in adults with T2DM. Xultophy is a once-daily, titratable subcutaneous injection for adults with T2DM that is not adequately controlled with insulin or liraglutide; it is a combination of Tresiba (degludec, a long-acting insulin) plus Victoza (GLP-1RA liraglutide), a combination that reduces the risk of hypoglycemia and weight gain, she said. However, it carries a boxed FDA warning about a risk of thyroid c-cell tumors, including medullary thyroid tumors.

The FDA is anticipated to approve three more diabetes drugs in 2017: MK-1293 (Merck), a subcutaneously-injected “follow-on biologic of insulin glargine” for T1DM and T2DM, which would be the third glargine product on the market; semaglutide (Novo Nordisk), a once-weekly subcutaneous injection for T2DM, and ertugliflozin (Merck/Pfizer) for T2DM, an oral sodium glucose cotransporter 2 (SGLT2) inhibitor. If approved, ertugliflozin would be the fourth SGLT2 inhibitor on the market, Kao noted.