FDA Activity Tracker: Top Approvals of 2019 to Date

A novel antibiotic for community-acquired bacterial pneumonia, a vaccine for dengue fever, a therapeutic for complicated urinary tract infections—the first half of the year has been a busy one when it comes to US Food and Drug Administration (FDA) activity in the infectious disease specialty.

Now, as the summer comes to a close, our editorial team is looking back at the top FDA approvals for infectious diseases of 2019 to date and looking ahead at what is left on the docket this year.

1. Dolutegravir + lamivudine (Dovato)

In April, the FDA issued an approval for dolutegravir and lamivudine (Dovato), as a complete regimen for treatment-naïve adults with HIV-1.

This marked the first FDA-approved 2-drug, fixed-dose, complete regimen for treatment-naïve adults with HIV.

"Currently, the standard of care for patients who have never been treated is a 3-drug regimen. With this approval, patients who have never been treated have the option of taking a 2-drug regimen in a single tablet while eliminating additional toxicity and potential drug interactions from a third drug," Debra Birnkrant, MD, director of the Division of Antiviral Products at the FDA’s Office of Antimicrobial Products, said in a statement. "Having a drug-sparing treatment available that uses fewer drugs is beneficial to patients who may have issues taking multiple medications over a long period of time."

Read the full article here.

2. Dengvaxia vaccine

In May, the FDA approved the vaccine Dengvaxia for the prevention of dengue disease in children aged 9 to 16 years with a laboratory-confirmed case of previous dengue infection. Eligible individuals must live in an endemic region of the United States, which include American Samoa, Guam, Puerto Rico and the US Virgin Islands.

Dengvaxia, produced by Sanofi Pasteur, is a live, attenuated vaccine, with an initial dose administered followed by 2 additional shots given 6 and 12 months later.

Dengvaxia is not approved for use in individuals who have not previously been infected by any serotype of dengue or for those without serological proof of illness. The reason behind this is, according to the FDA's statement, is that Dengvaxia "appears to act as a first dengue infection, without actually infecting the person with wild-type dengue virus—such that a subsequent infection can result in severe dengue disease."

Read the full article here.

3. Ceftolozane/tazobactam (Zerbaxa)

In June, the FDA approved ceftolozane/tazobactam for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP). The approval of this new indication was granted to Merck & Co., Inc.

Ceftolozane/tazobactam (Zerbaxa) is a combination treatment of an anti-pseudomonal cephalosporin, ceftolozane, and an extended-spectrum β-lactamase inhibitor, tazobactam. In the United States ceftolozane/tazobactam is indicated for the treatment of complicated urinary tract infections including pyelonephritis caused by certain susceptible Gram-negative microorganisms and also in combination with metronidazole for the treatment of complicated intra-abdominal infections. It was first approved by the FDA in 2014.

In February, the FDA accepted the supplemental New Drug Application (sNDA) of ceftolozane/tazobactam for priority review to treat patients with nosocomial pneumonia. The acceptance of the sNDA was based on the findings of the ASPECT-NP trial.

Read the full article here.

4. Imipenem/Cilastatin + Relebactam (Recarbrio)

In July, the FDA approved imipenem/cilastatin + relebactam (Recarbrio) for the treatment of complicated urinary tract infections and complicated intra-abdominal bacterial infections in adults who have limited or no alternative treatments available.

An NDA was accepted in February for the combination of relebactam, Merck’s investigational beta-lactamase inhibitor, with imipenem/cilastatin for the treatment of complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI) caused by certain susceptible gram-negative bacteria.

Recarbrio is indicated in patients 18 years of age and older who have limited or no alternative treatment options, for the treatment of cUTI, including pyelonephritis, caused by the following susceptible gram-negative microorganisms: Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae, and Pseudomonas aeruginosa. It is also indicated for the treatment of cIAI caused by the following susceptible gram-negative microorganisms: Bacteroides caccae, Bacteroides fragilis, Bacteroides ovatus, Bacteroides stercoris, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Fusobacterium nucleatum, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Parabacteroides distasonis and Pseudomonas aeruginosa.

Read the full article here.

5. Lefamulin (Xenleta)

Earlier this month, the FDA approved lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia (CABP) after results from 2 phase 3 studies showed the novel pleuromutilin antibiotic to be non-inferior to existing treatment options.

“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease,” said Ed Cox, MD, MPH, director of FDA’s Office of Antimicrobial Products in a statement issued by the FDA. “For managing this serious disease, it is important for physicians and patients to have treatment options. This approval reinforces our ongoing commitment to address treatment of infectious diseases by facilitating the development of new antibiotics.”

In total, the efficacy of lefamulin was evaluated in 1289 patients with CABP. In the LEAP 1 trial, IV to oral lefamulin was found to be non-inferior to IV to oral moxifloxacin with or without linezolid. In LEAP 2, lefamulin again successfully met the FDA primary endpoint of non-inferiority compared with moxifloxacin for early clinical response, which was evaluated in the intent-to-treat patient population 72 to 120 hours after treatment was initiated.

Read the full article here.

In addition to these 5 approvals, the FDA has issued 2 Complete Response Letters (CRL) so far this year.

1. Iclaprim

In February, the FDA issued a CRL to Motif Bio for iclaprim for the treatment of acute bacterial skin and skin structure infections (ABSSI) based on the need for additional data.

Iclaprim has a targeted Gram-positive spectrum of activity, which can decrease the use of broad-spectrum antibiotics to avoid resistance build-up, and reduce the impact on the microbiome. According to the FDA, more data is needed to evaluate the risk for liver toxicity before the approval of the NDA.

Motif Bio and the FDA are scheduled to meet next month to discuss a proposed additional clinical study.

Read the full article here.

2. Fosfomycin for injection (Contepo)

In late April, the FDA issued a CRL to Nabriva Therapeutics for intravenous fosfomycin (Contepo) for the treatment of complicated urinary tract infections (cUTI), including acute pyelonephritis.

According to a press release, the CRL requests that Nabriva address issues related to facility inspections and manufacturing deficiencies at one of Nabriva’s contract manufacturers prior to the FDA approving the New Drug Application. The FDA did not request any new clinical data and did not raise any concerns with regard to the safety of Contepo.

Earlier this month, Nabriva announced plans to resubmit the NDA for intravenous fosfomycin early in quarter 4 of 2019.

Read the full article here.

Here is a look at upcoming Prescription Drug User Fee Act (PFUDA) dates for the rest of 2019 for infectious diseases:

September 20, 2019

Drug: Delstrigo (Doravirine/lamivudine/tenofovir disoproxil/fumarate)

Company: Merck

Disease: HIV

Notes: Supplemental new drug application for Delstrigo as a switch therapy

September 20, 2019

Drug: Pifeltro (doravirine)

Company: Merck

Disease: HIV

Notes: Supplemental new drug application for Pifeltro as a switch therapy

October 24, 2019

Drug: Baxdela (delafloxacin)

Company: Melinta Therapeutics

Disease: Community-acquired bacterial pneumonia

Notes: Expanded indication

November 2, 2019

Drug: Talicia (RHB-105)

Company: Redhill Biopharma

Disease: Helicobacter pylori

November 4, 2019

Drug: Baloxavir marboxil

Company: Roche

Disease: Complicated influenza

Notes: Supplemental new drug application

December 29, 2019

Drug: Cabotegravir/rilpivirine injectable

Company: Viiv/Janssen

Disease: HIV

Notes: Monthly, injectable, two-drug regimen of ViiV Healthcare’s cabotegravir and Janssen’s rilpivirine to treat HIV-1 infection in adults whose viral load is suppressed