Through 2016, the FDA approved a range of medications, including 69 new medications or medication formulations, and 10 new indications for existing medications. Of the 69 approvals, 12 new products or medications are indicated to treat conditions related to infectious diseases (Table 1), and two more such approvals are expected by the end of 2016 (Table 2). Prominent among these approvals are medications for treatment of infections of hepatitis C virus (HCV), human immunodeficiency virus (HIV), and hepatitis B virus (HBV). Together, medications to treat these infections account for more than half (7) of 12 new infectious disease products approved in 2016.1
On January 28, 2016, Merck’s Zepatier (elbasvir/ grazoprevir) was approved for treatment of chronic HCV genotypes 1 or 4 infection in adults. Zepatier differs from other direct-acting antivirals in that it can be used in patients with any degree of renal impairment, including patients with end-stage renal disease receiving hemodialysis. A course of therapy ranges from 12 to 18 weeks’ duration, and may or may not require use of ribavirin. Use is contraindicated in patients with moderate to severe hepatic impairment, and in patients taking OATP1B1/3 inhibitors (eg, atazanavir, darunavir, lopinavir, saquinavir, tipranavir, and cyclosporine), strong CYP3A inducers, and efavirenz.1,2
Five months after the approval of Zepatier, on June 28, 2016, the FDA approved Gilead’s Epclusa (sofosbuvir/ veltapasvir). Epclusa is unique among direct-acting antivirals in that it is indicated for the treatment of adult patients with chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection. The duration of therapy is 12 weeks, either with Epclusa alone (in patients with Child-Pugh class A cirrhosis), or with the combination of Epclusa and ribavirin (in patients with Child-Pugh class B or C cirrhosis). There are no contraindications for use of Epclusa beyond those that apply to ribavirin.1,3 Read more about Epclusa here.
Following Epclusa, on July 22, 2016, the FDA approved AbbVie’s Viekira XR (dasabuvir sodium/ ombitasvir/paritaprevir/ritonavir), which is a once daily formulation of the previously approved twice daily Viekira Pak. Use of Viekira Pak required taking two combination tablets of ombitasvir, paritaprevir, ritonavir in the morning, and one tablet of dasabuvir twice daily, for a total of four tablets daily (three in the morning and one at night). With Viekira XR, the pill burden is reduced to three tablets, administered as a single daily dose. In some patients, Viekira XR must be used with ribavirin. Notably, as ribavirin is typically taken twice daily, the dosing advantage of Viekira XR over Viekira Pak is largely eliminated in these patients.1,4,5
Although the formulation of Viekira has changed, the medication is still approved for use only in patients with genotype 1 HCV infection. Contraindications include use in patients with moderate to severe hepatic impairment (Child-Pugh class B or C cirrhosis); use in patients with a known hypersensitivity to ritonavir; and coadministration with drugs that are highly dependent on CYP3A for clearance, moderate or strong inducers of CYP3A or strong inducers of CYP2C8, or strong inhibitors of CYP2C8.4,5
Table 1: New Medications Approved in 2016
Zepatier (elbasvir/ grazoprevir)
Indicated with or without ribavirin for treatment of chronic HCV genotypes 1 or 4 infection in adults
Merck Sharpe & Dohme
Aczone (dapsone 7.5% gel)
Indicated for the topical treatment of acne vulgaris in patients 12 years and older
Odefsey (emtricitabine/rilpivirine HCl/tenofovir alafenamide fumarate)
Indicated as a complete regimen for the treatment of HIV-1 infection in patients 12 years and older as initial therapy in those with no antiretroviral
treatment history with HIV-1 RNA less than or equal to 100,000 copies per mL, or to replace a stable antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) for at least 6 months with
no history of treatment failure and no known substitutions associated with resistance to the individual components of Odefsey
Indicated in adult and pediatric patients for treatment of inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs, and for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate
Descovy (emtricitabine/tenofovir alafenamide fumarate)
Indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 12 years and older
Acticlate (doxycycline hyclate)
Indicated for treatment of rickettsial infections; sexually transmitted infections; respiratory tract infections; specific bacterial infections; ophthalmic infections; anthrax, including inhalational anthrax (postexposure); alternative treatment for selected infections when penicillin is contraindicated; adjunctive therapy for acute intestinal amebiasis and severe acne; prophylaxis of malaria
Otovel (ciprofloxacin HCl/fluocinolone
Indicated for the treatment of acute otitis media with tympanostomy tubes (AOMT) in pediatric patients (6 months and older) due to Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella
catarrhalis, and Pseudomonas aeruginosa
Epclusa (sofosbuvir/ velpatasvir)
Indicated for the treatment of adult patients with chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection
Viekira XR (dasabuvir sodium/ ombitasvir/ parita- previr/ritonavir)
Indicated for the treatment of adult patients with chronic hepatitis C virus, including genotype 1b infection without cirrhosis or with compensated cirrhosis, and genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin
Vaxchora (cholera vaccine, live oral)
Indicated for active immunization against disease caused by Vibrio cholerae serogroup O1; approved for use in adults 18 through 64 years of age traveling to cholera-affected areas
Indicated to reduce recurrence of Clostridium difficile infection (CDI) in patients 18 years or older who are receiving antibacterial drug treatment of CDI and are at a high risk for CDI recurrence
Merck Sharp & Dohme
Selzentry (maraviroc)— new indication
Indicated for pediatric use in patients 2 years or older weighing at least 10 kilograms
Vemlidy (tenofovir alafenamide)
Indicated for the treatment of chronic hepatitis B virus infection in adults with compensated liver disease
Gilead’s Odefsey (emtricitabine/rilpivirine HCl/ tenofovir alafenamide fumarate), which was approved on March 2, 2016, is indicated for treatment of HIV-1 infection in patients 12 years and older. Two of three components of Odefsey are identical to those of an earlier fixed-dose antiviral, Complera (emtricitabine/ rilpivirine HCl/tenofovir disoproxil fumarate). Patients receiving the combination containing tenofovir alafenamide fumarate showed lower rates of bone mineral density loss, and lower rates of proteinuria than patients receiving the combination containing tenofovir disoproxil fumarate.6-8
A two-drug combination, Descovy (emtricitabine/ tenofovir alafenamide fumarate) was approved approximately 1 month after Odefsey, on April 4, 2016. Unlike Odefsey, Descovy is not indicated for use as a single-tablet regimen, but is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older. In clinical trials, compared with its tenofovir disoproxil fumarate— containing counterpart, Truvada (emtricitabine/ tenofovir disoproxil fumarate), Descovy showed lower rates of bone mineral density loss and superior renal outcomes.6,9-11
Additionally, approval for an existing medication, the CCR5 co-receptor antagonist Selzentry (maraviroc), was extended on November 4, 2016, when the treatment was approved for use in children aged 2 years or older weighing at least 10 kg. Previously, the medication was only indicated for use in adults aged 18 years or older.1,12,13
On November 10, 2016, Gilead received approval for Vemlidy (tenofovir alafenamide) for treatment of chronic HBV infection in patients with compensated liver disease. Compared with Viread (tenofovir disoproxil fumarate), which is also approved for treatment of chronic HBV infection, Vemlidy is more stable in plasma, delivers tenofovir to liver cells more efficiently, and has demonstrated improved renal and bone laboratory safety parameters versus Viread in clinical studies.14,15
Although it has not yet been approved, a new vaccine for hepatitis B—Dynavax’s Heplisav-B (hepatitis B vaccine, recombinant [adjuvanted])—is expected to be approved by the end of the year, based on a prescription drug user fee act (PDUFA) date of December 15, 2016. Results of phase 3 trials with Heplisav-B indicate that the medication may offer earlier protection against HBV infection with fewer doses than existing vaccines.16
Reformulations of existing medications approved as new drugs include Aczone (dapsone) gel 7.5% (Allergan), which was previously available only in the 5% strength; Acticlate (doxycycline hyclate) tablets (Aqua) for acne vulgaris, which has been available in the United States since 1967; and Otovel (ciprofloxacin HCl/fluocinolone acetonide) drops (Arbor), which substitutes the glucocorticoid component in existing ciprofloxacin-containing combination drops for a different corticosteroid.17-19
Contrasting with these products, medications that represent important advances include Elusys’ Anthim (obiltoxaximab solution), a monoclonal antibody product that was approved for treatment of inhalational anthrax; PaxVax’s Vaxchora (cholera vaccine, live oral) for prevention of disease caused by Vibrio cholerae serogroup O1 in adults aged 18 through 64 years traveling to cholera-affected areas; and Merck’s Zinplava (bezlotoxumab) for reducing Clostridium difficile infection (CDI) recurrence in patients 18 years of age or older at a high risk for CDI recurrence receiving antibacterial drug treatment of CDI.20-22
Looking forward to FDA decisions in late 2016 and early 2017, prospects for infectious disease approvals are, unfortunately, relatively paltry. An FDA decision on Dynavax’s Heplisav-B (hepatitis B vaccine, recombinant [adjuvanted]) is expected December 15, 2016, followed by Cempra’s Solithera (solithromycin) for community-acquired bacterial pneumonia on December 27, 2016. At this time, a PDUFA date has been assigned for only one other product with an infectious disease indication (ozenoxacin cream 1% by Medimetriks for impetigo).16,23,24
Table 2: FDA Decisions Expected in Late 2016 Through Early 2017
Heplisav-B (Hepatitis B Vaccine, Recombinant [Adjuvanted])
Prevention of hepatitis B virus infection
Community-acquired bacterial pneumonia
Ozenoxacin cream 1%
Medimetriks Pharmaceuticals, Inc
PDUFA, Prescription Drug User Fee Act
Although three of the 12 approvals in 2016 were not major therapeutic advances, the remaining 9 approvals for new products, and one new indication represent an impressive set of advances. With products that improve the safety profile of existing medications, fulfill unmet therapeutic needs, and offering additional modalities for disease prevention, patients with many infectious disease—related conditions stand to benefit from timely FDA approvals in 2016 and beyond.
1. US Food and Drug Administration. Approvals of FDA-regulated products. FDA website. www.fda.gov/NewsEvents/ProductsApprovals/. Accessed November 2016.
2. ZEPATIER (elbasvir and grazoprevir) [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; 2016.
3. EPCLUSA (velpatasvir and sofosbuvir) [prescribing information]. Foster City, CA: Gilead Sciences, Inc; 2016.
4. VIEKIRA XR (dasabuvir and ombitasvir and paritaprevir and ritonavir) [prescribing information]. North Chicago, IL: AbbVie, Inc; 2016.
5. VIEKIRA PAK (dasabuvir and ombitasvir and paritaprevir and ritonavir) [prescribing information]. North Chicago, IL: AbbVie, Inc; 2016.
6. ODEFSEY (emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate) [prescribing information]. Foster City, CA: Gilead Sciences, Inc; 2016.
7. COMPLERA (emtricitabine, rilpivirine hydrochloride, and tenofovir disoproxil fumarate) [prescribing information]. Foster City, CA: Gilead Sciences, Inc; 2016.
8. Gilead’s odefsey (emtricitabine, rilpivirine, tenofovir alafenamide) meets primary 48-week objective in two phase 3b studies [press release]. Foster City, CA: Gilead. July 21, 2016. www.gilead.com/ news/press-releases/2016/7/gileads-odefsey-emtricitabinerilpivirine- tenofovir-alafenamide-meets-primary-48week-objectivein- two-phase-3b-studies. Accessed November 2016.
9. DESCOVY (emtricitabine and tenofovir alafenamide fumarate) [prescribing information]. Foster City, CA: Gilead Sciences, Inc; 2016.
10. TRUVADA (emtricitabine and tenofovir disoproxil fumarate). Foster City, CA: Gilead Sciences, Inc; 2016.
11. Gilead presents results from phase 3 studies evaluating switching to descovy (FTC/TAF)-based regimens from truvada (FTC/TDF)- based regimens [press release]. Foster City, CA: Gilead. October 24, 2016. www.gilead.com/news/press-releases/2016/10/gileadpresents- results-from-phase-3-studies-evaluating-switching-todescovy- ftctafbased-regimens-from-truvada-ftctdfbased-regimens. Accessed November 2016.
12. SELZENTRY (maraviroc) [prescribing information]. Research Triangle Park, NC: ViiV Healthcare; 2016.
13. Page MR. Selzentry for children as young as 2 years: details and therapeutic relevance. Contagion website. www.contagionlive. com/news/selzentry-for-children-as-young-as-2-years-detailsand- therapeutic-relevance. Published November 8, 2016. Accessed November 2016.
14. VEMLIDY (tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences, Inc; 2016.
15. VIREAD (tenofovir disoproxil fumarate) [prescribing information]. Foster City, CA: Gilead Sciences, Inc; 2016.
16. Dynavax provides regulatory update on HEPLISAV-B: PDUFA date of December 15, 2016, remains unchanged [press release]. Berkeley, CA: Dynavax. September 4, 2016. http://investors.dynavax. com/releasedetail.cfm?releaseid=987707. Accessed November 2016. 17. ACZONE GEL 7.5% (dapsone) [prescribing information]. Irvine, CA: Allergan, Inc; 2016. 18. ACTICLATE (doxycycline hyclate) [prescribing information]. West Chester, PA: Aqua Pharmaceuticals; 2016.
19. OTOVEL (ciprofloxacin and fluocinolone acetonide) [prescribing information]. West Chester, PA: Arbor Pharmaceuticals (under license from Laboratorios SALVAT, S.A.); 2016. 20. ANTHIM (obiltoxaximab) [prescribing information]. Pine Brook, NJ: Elusys Therapeutics, Inc; 2016.
21. VAXCHORA (cholera vaccine, live, oral) [prescribing information]. Redwood City, CA: Paxvax, Inc; 2016.
22. ZINPLAVA (bezlotoxumab) [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; 2016.
23. Cempra announces FDA acceptance of solithera new drug applications in the treatment of community-acquired bacterial pneumonia [press release]. Chapel Hill, NC: Cempra; July 5, 2016. http://investor.cempra.com/releasedetail.cfm?ReleaseID=978096. Accessed November 2016.
24. Medimetriks Pharmaceuticals’ new drug application for ozenoxacin cream, 1% accepted for review by FDA [press release]. Fairfield, NJ: PRNewswire; August 31, 2016. www.prnewswire. com/news-releases/medimetriks-pharmaceuticals-new-drugapplication- for-ozenoxacin-cream-1-accepted-for-review-byfda- 300320125.html. Accessed November 2016.