1. U.S. Food and Drug Administration. Novel Drugs Summary 2016. January 4, 2017.
  2. Ahren B, et al. Postprandial glucagon reductions correlate to reductions in postprandial glucose and glycated hemoglobin with lixisenatide treatment in type 2 diabetes mellitus: A Post Hoc Analysis. Diabetes Ther. 2016 Jun 18.
  3. Yabe D, et al. Efficacy of lixisenatide in patients with type 2 diabetes: A post hoc analysis of patients with diverse β-cell function in the GetGoal-M and GetGoal-S trials. J Diabetes Complications. 2016 May 24.
  4. Pfeffer MA, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015 Dec 3;373(23):2247-57.
  5. Edwards JE, et al. Exposure-response relationship of obeticholic acid for alkaline phosphatase and total bilirubin in patients with primary biliary cirrhosis. Presented at Digestive Disease Week. May 21, 2016. San Diego, CA.
  6. Zeuzem S, et al. Grazoprevir–Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med. 2015;163(1):1-13.
  7. Buti M, et al. Grazoprevir, Elbasvir, and Ribavirin for Chronic Hepatitis C Virus Genotype 1 Infection After Failure of Pegylated Interferon and Ribavirin With an Earlier-Generation Protease Inhibitor: Final 24-Week Results From C-SALVAGE. Clin Infect Dis. 2016 Jan 1;62(1):32-6.
  8. Foster GR, et al. Astral-2 and -3 Investigators. Sofosbuvir and velpatasvir for HCV genotypes 2 and 3 infection. N Engl J Med. 2015 Dec 31;373(27):2608-17.
  9. Feld JJ, et al. Astral-1 Investigators. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med. 2015 Dec 31;373(27):2599-607.
  10. Curry MP, et al. Astral-4 Investigators. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015 Dec 31;373(27):2618-28.
  11. Venclexta (venetoclax) prescribing information. AbbVie, Inc. North Chicago, IL. April 2016.
  12. U.S. Food and Drug Administration. FDA News Release: FDA grants accelerated approval to new treatment for advanced ovarian cancer. 2016 Dec 19. Available at
  13. Mulcahy N. FDA Approves Rucaparib for BRCA Ovarian Cancer. Medscape Medical News. WebMD Inc. 2016 Dec 19. Available at
  14. Rubraca (rucaparib) prescribing information. Clovis Oncology, Inc. Boulder, CO. 2016 December. Available at
  15. Rosenberg JE, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 Mar 4. pii: S0140-6736(16)00561-4.
  16. Tap WD, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97.
  17. Odewole OA, et al. Recurrent prostate cancer detection with anti-3-[18F]FACBC PET/CT: comparison with CT. Eur J Nucl Med Mol Imaging. 2016 Apr 18.
  18. Van Binnebeek S, et al. Comparison of diagnostic accuracy of (111)In-pentetreotide SPECT and (68)Ga-DOTATOC PET/CT: A lesion-by-lesion analysis in patients with metastatic neuroendocrine tumours. Eur Radiol. 2016 Mar;26(3):900-9.
  19. Richardson PG, et al. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. Blood. 2016 Jan 29.
  20. A Phase 3, Randomized, Double-blind, Sham-Procedure Controlled Study to Assess the Clinical Efficacy and Safety of ISIS 396443 Administered Intrathecally in Patients With Infantile-onset Spinal Muscular Atrophy - ENDEAR trial. Presented at the British Paediatric Neurology Association (BPNA) Annual Conference in January 2017. Clinical identifier: NCT02193074
  21. Klein P, et al. A randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with uncontrolled partial-onset seizures. Epilepsia. 2015 Dec;56(12):1890-98
  22. Cummings J, et al. Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. 2014 Feb 8;383(9916):533-40.
  23. Kappos L, et al. Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2015 Oct 8;373(15):1418-28.
  24. Gold R, et al. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial. Lancet. 2013 Jun 22;381(9884):2167-75.
  25. Mendell JR, et al. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013 Nov;74(5):637-47.
  26. Mendell JR, et al. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016 Feb;79(2):257-71.
  27. Castro M, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015 May;3(5):355-66.
  28. Anthim (obiltoxaximab) prescribing information. Elusys Therapeutics, Inc. Pine Brook, NJ.
  29. Kelly CP, et al. The monoclonal antibody, bezlotoxumab targeting C. difficile toxin B shows efficacy in preventing recurrent C. difficile infection (CDI) in patients at high risk of recurrence or of CDI-related adverse outcomes. Gastroenterology. 2016 150:4 SUPPL. 1 (S122). Presented at Digestive Disease Week May 21-24, 2016. San Diego.
  30. Griffiths CE, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015 Aug 8;386(9993):541-51.
  31. Paller, AS, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016 Sep;75(3):494-503.
  32. Holland EJ, et al. Lifitegrast clinical efficacy for treatment of signs and symptoms of dry eye disease across three randomized controlled trials. Curr Med Res Opin. 2016 Jul 8:1-24.
  33. Sheppard JD, et al. Lifitegrast ophthalmic solution 5% for treatment of dry eye disease: results of the OPUS-1 phase 3 study. Ophthalmology. 2014 Feb;121(2):475-83.
  34. Tauber J, et al. Lifitegrast ophthalmic solution 5% versus placebo for treatment of dry eye disease: Results of the randomized phase III OPUS-2 study. Ophthalmology. 2015 Dec;122(12):2423-31.
  35. Donnefeld ED, et al. Safety of lifitegrast ophthalmic solution 5% in patients with dry eye disease: A 1-year, multicenter, randomized, placebo-controlled study. Cornea. 2016 Jun;35(6):741-8.

Contributor Information


Mary L Windle, PharmD
Editor-in-Chief, Medscape Drug Reference


Close<< Medscape

FDA Drug and Biologic Approvals: 2016 Year-in-Review

Mary L Windle, PharmD  |  January 20, 2017

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Approval was based on results from the GetGoal clinical program and findings from the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trials. The GetGoal worldwide clinical program included 13 clinical trials of adults with type 2 diabetes mellitus (N>5000) and evaluated safety and efficacy. All studies of the GetGoal program successfully met the primary efficacy endpoint of HbA1c reduction.[2,3] The ELIXA study showed that in patients with type 2 diabetes who had a recent acute coronary syndrome, lixisenatide did not lead to increased cardiovascular adverse events compared with placebo.[4]

See the Adlyxin (lixisenatide) drug monograph.

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Approval was based on the POISE trial in patients with PBC (N=216). The study included patients who had not shown a reduction in alkaline phosphatase (ALP) levels with UDCA at optimal dosage for at least 1 yr or as monotherapy in those who were intolerant to UDCA. The primary endpoint (ie, ALP <1.67 x ULN) was met in 47% of the obeticholic acid 10 mg group and 46% in the titration group (ie, 5-10 mg), compared with 10% in the placebo plus UDCA group (P<0.0001).[5]

See the Ocaliva (obeticholic acid) drug monograph.

Slide 7

Efficacy was evaluated in clinical trials that included nearly 1400 patients. The overall SVR (sustained virologic response) rates were 94-97% for genotype 1 and 97-100% for genotype 4 across trials.[6,7]

See the Zepatier (elbasvir/grazoprevir) drug monograph.

Slide 8

Approval was based on 4 international phase 3 studies, ASTRAL-1, ASTRAL-2, ASTRAL-3, and ASTRAL-4. In the ASTRAL-1, ASTRAL-2, and ASTRAL-3 studies, 1035 patients with genotype 1-6 chronic HCV infection without cirrhosis or with compensated cirrhosis received 12 wk of sofosbuvir/velpatasvir.[8,9] These studies showed a high sustained virologic response at 12 wk with sofosbuvir/velpatasvir (94-99%) compared with sofosbuvir plus ribavirin (80-94%). The ASTRAL-4 study randomized 267 patients with genotype 1-6 HCV infection with decompensated cirrhosis (Child-Pugh B) to receive sofosbuvir/velpatasvir for 12 wk with or without RBV or as monotherapy for 24 wk.[10]

See the Epclusa (sofosbuvir/velpatasvir) drug monograph.

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Slide 10

Approval was based on an open-label, multicenter clinical trial of 106 previously treated patients with CLL and 17p deletion. The primary efficacy endpoint, overall response rate (ORR), was 80%. The median time to first response was 0.8 mo (range: 0.1 to 8.1 mo). Median duration of response (DOR) has not been reached with approximately 12 mo of median follow-up.[11]

See the Venclexta (venetoclax) drug monograph.

Slide 11

Approval was based on results from 106 women enrolled in 2 single-arm clinical trials: Study 10 and ARIEL2 (Assessment of Rucaparib In Ovarian CancEr TriaL2). Patients in these trials had an overall response rate of 54% (complete, 9%; partial, 45%) and a median duration of response of 9.2 mo, according to the FDA press materials. The drug's prescribing information also indicates that the overall response rate as assessed by an independent radiology review was 42%, with a median duration of response of 6.7 mo, while the investigator-assessed response rate was 66%.[12-14]

See the Rubraca (rucaparib) drug monograph.

Slide 12

Approval was based on a safety and efficacy analysis of the phase 2 IMvigor 210 trial (N=310). The objective response rate was 15% for all patients, 26% for the highest expression for PD-L1, and 18% for the lowest expression. Median overall survival was 7.9 mo, and 12-mo overall survival was 36%.[15]

See the Tecentriq (atezolizumab) drug monograph.

Slide 13

Accelerated approval was based on a phase 2 trial (N=133). Overall survival was significantly improved with olaratumab plus doxorubicin compared with doxorubicin alone (26.5 mo vs 14.7 mo; P=0.0003). Progression-free survival (PFS) and tumor shrinkage (TS) were improved with the combination (PFS, 8.2 mo vs 4.4 mo; TS, 18.2% vs 7.5%).[16]

See the Lartruvo (olaratumab) drug monograph.

Slide 14

Approval was based on a comparative trial with 11C-choline. Sensitivity rates for 11C-choline and fluciclovine F 18 were 32% vs 37%; specificity rates, 40% vs 67%; accuracy rates, 32% vs 38%; and positive predictive values (PPVs), 90% vs 97%.[5] Another trial observed that the diagnostic performance of fluciclovine PET/CT in recurrent prostate cancer was superior to that of CT, and also observed that fluciclovine PET/CT provided better delineation of prostatic recurrence and extraprostatic recurrence.[17]

See the Axumin (fluciclovine F 18) drug monograph.

Slide 15

Approval was based on 3 trials (N=265) conducted in adults who had known or suspected NETs. The trials compared gallium Ga 68-dota-tate images of NETs to images obtained with an approved drug, and then confirmed with CT and/or MRI. The second trial evaluated gallium Ga 68-dota-tate images using histopathology or clinical follow-up as reference standards. The third trial evaluated patients with NET recurrence using gallium Ga-68-dota-tate images. The results of all 3 studies confirmed the usefulness of gallium Ga-68-dota-tate images in finding the location of the neuroendocrine tumors.[18]

See the Netspot (gallium Ga 68-dota-tate) drug monograph.

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Approval was based on findings of a phase 3 trial (N = 102) that observed significant improvement in survival with defibrotide compared to 32 historical controls. Survival at day +100 post-HSCT was 38.2% for the defibrotide group and 25% for the control group (estimated difference of 230%; 95.1% confidence interval [CI] 5.2-40.8%; P=0.0109, using a propensity-adjusted analysis based on 4 prognostic factors of survival).[19]

See the Defitelio (defibrotide) drug monograph.

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Approval was based on interim results from the ENDEAR trial (N=121) in patients with infantile-onset SMA. A greater percentage of infants treated with nusinersen achieved a motor milestone response compared to those who did not receive treatment (40% vs 0%; P<0.0001) as measured by the Hammersmith Infant Neurological Examination (HINE). Additionally, a smaller percentage of patients in the nusinersen group died (23%) compared to untreated patients (43%).[20]

See the Spinraza (nusinersen) drug monograph.

Slide 20

Approval was based on results from a randomized, double-blind, placebo-controlled, multicenter study (N=768) that enrolled patients with uncontrolled POS despite ongoing treatment with 1-2 antiepileptic drugs. Percent reduction in POS, compared with placebo, was 22.8% for brivaracetam 100 mg/day and 23.2% for brivaracetam 200 mg/day (P<0.001).[21]

See the Briviact (brivaracetam) drug monograph.

Slide 21

Approval was based on a 6-wk clinical trial (N=199), where pimavanserin was shown to be superior to placebo in decreasing the frequency and/or severity of hallucinations and delusions without worsening the primary motor symptoms of Parkinson disease (P=0.001).[22]

See the Nuplazid (pimavanserin) drug monograph.

Slide 22

Approval was based on results from 2 trials, DECIDE and SELECT, in which daclizumab 150 mg was administered SC every 4 wk in people with relapsing-remitting MS. In the DECIDE trial, daclizumab was compared with interferon beta-1a (30 mcg/wk IM). The annualized relapse rate was lower with daclizumab than with interferon beta-1a (0.22 vs. 0.39; 45% lower rate with daclizumab; P<0.001).[23] The SELECT trial showed that the annualized relapse rate was lower for patients given daclizumab than those given placebo (54% reduction, 95% confidence interval [CI], 33-68%; P<0.0001).[24]

See the Zinbryta (daclizumab) drug monograph.

Slide 23

Accelerated approval was based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some treated patients.[25] A 36-mo extension of this trial showed eteplirsen-treated patients (N=12) demonstrated a statistically significant advantage of 151m (P<0.01) on 6-min walking tests and experienced a lower incidence of loss of ambulation in comparison to matched historical controls (N=13).[26] Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.

See the Exondys 51 (eteplirsen) drug monograph.

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Approval was based on 3 multicenter, international trials in patients with asthma who had elevated eosinophils. In 2 of these studies (N=953), patients who received reslizumab had a significant reduction in the frequency of asthma exacerbations of up to 59% (study 1: rate ratio [RR] 0.50 [95% CI 0.37-0.67]; study 2: 0.41 [0.28-0.59]; both P<0.0001) compared with those receiving placebo.[27]

See the Cinqair (reslizumab) drug monograph.

Slide 26
Slide 27

Because it is not feasible or ethical to conduct controlled clinical trials in humans with inhalational anthrax, efficacy was based on efficacy studies in New Zealand white rabbits and the cynomolgus macaque. Additionally, pharmacokinetic and safety trials were conducted in healthy adult volunteers. Pediatric dosage was extrapolated with pharmacokinetic-based information.[28]

See the Anthim (obiltoxaximab) drug monograph.

Slide 28

Approval was based on results from the global MODIFY I and MODIFY II studies, which showed a single dose of bezlotoxumab (in conjunction with antibiotics) is superior to placebo in prevention of CDI recurrence through 12 wk (P=0.0003 for both trials).[29]

See the Zinplava (bezlotoxumab) drug monograph.

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Approval was based on 2 prospective, double-blind, multicenter phase 3 trials (UNCOVER 2, UNCOVER 3) that compared ixekizumab to placebo and etanercept. Ixekizumab (every 2 wk or 4 wk) showed greater efficacy (measured by PASI 75 [Psoriasis and Severity Index 75% reduction]) compared with placebo or etanercept (P<0.0001). Greater proportions of patients given ixekizumab achieved PASI 90 by week 2 compared with etanercept in both studies (UNCOVER 2: P=0.0002 [ixekizumab every 4 wk] and P<0.0001 [ixekizumab every 2 wk]; UNCOVER 3: P<0.0001 [ixekizumab every 4 wk] and P=0.0001 [ixekizumab every 2 wk]).[30]

See the Taltz (ixekizumab) drug monograph.

Slide 31

Approval was based on 2 prospective, double-blind, multicenter phase 3 trials. Patients who received crisaborole achieved a greater response with clear or almost clear skin after 28 days, compared with vehicle-treated patients (P<0.001).[31]

See the Eucrisa (crisaborole topical) drug monograph.

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Approval was based on four phase 3 trials (N>2500): OPUS-1, OPUS-2, OPUS-3, and one long-term (1-yr) phase 3 safety study (SONATA).[32-35] Lifitegrast improved inferior corneal staining score (ICSS) in the OPUS-1 and OPUS-3 studies.[32,33] Ocular safety and tolerability were similar to placebo.[35]

See the Xiidra (lifitegrast) drug monograph.

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