In 2016, novel medications approved by the FDA decreased from the encouraging tally of 45 that we saw last year to 22, the lowest it has been since 2010
In 2016, novel medications approved by the FDA decreased from the encouraging tally of 45 that we saw last year to 22, the lowest it has been since 2010. Although early approvals late in 2015 and delays to end 2016 have been used to justify the lagging productivity, pharmaceutical returns on research and development fell to 3.7% in 2016 from the high of 10.1% observed in 2010.1
But, without further adieu, here are the new approvals and what you should know about them:2,3
1. Adlyxin® (lixisenatide, Sanofi®)
As another glucagon-like peptide-1 (GLP-1) agonist enters the market, the real question is how will it stand out amongst other available options? Using 2 different titration methods, lixisenatide monotherapy, in combination with other antidiabetic agents showed superiority to placebo in glycated hemoglobin (HbA1c) decrease (~0.8% versus 0.27%). In addition, lixisenatide proved non-inferior to exanatide, with both regimens including metformin, and had a better tolerability profile. Dosing should start at 10 mcg daily for 14 days with an increase to 20 mcg starting after the initial 2 weeks.
2. Anthim® (obiltoxaximab, Elusys Therapeutics®)
With an indication for inhaled anthrax and backing from the Department of Health and Human Services, this medication serves as a tool to counter potential bioterrorist attacks. Obiltoxaximab is an immunoglobulin G1 (IgG1) monoclonal antibody that binds Bacillus anthracis to prevent it from binding receptors in the human body. By preventing lethal and edema factor development, toxic components that lead to pathogenic effects are inhibited. Dosing is weight-based (16-32 mg/kg) and intravenously administered over 90 minutes.
3. Axumin® (fluciclovine F 18, Blue Earth Diagnostics®)
Where prostate-specific antigen (PSA) testing falls short, Axumin® has the potential to step up. As recurrent prostate cancer is normally diagnosed with rises in the PSA level, the extent and location cannot be identified. This molecular imaging agent is used in positron emission tomography (PET) scans for identifying areas of potential recurrent prostate cancer. The medication is a synthetic amino acid that is transported across cell membranes and will be transported more actively in locations with higher prostate cancer activity. The normal dose is 10 millicuries as a single IV bolus.
4. Briviact® (brivaracetam, UCB®)
With no shortage of epilepsy medications in current existence, what can Briviact® bring to the market? Varied individual response to seizure medications and the elimination of a built-in titration period may be 2 reasons the FDA was convinced to approve this new agent. There is no clear mechanism, but binding affinity was stated to be high and selective for the synaptic vesicle protein 2A in the brain. Administration is available via oral and intravenous routes, starting at 100 mg per day and titrating to between 50 and 200 mg per day based on clinical response.
5. Cinqair® (reslizumab, Teva®)
A typical diagnostic workup of asthma may now include phenotyping, and Cinqair® is approved as an add-on specifically for the eosinophilic class. Randomized clinical trials found significant decline in exacerbations at 52 weeks, significant change in FEV1 levels at 16 weeks, and significant improvement in asthma control and quality of life as reported by patients. Even with positive findings, there is stiff competition as this is only available intravenously and competing eosinophilic asthma agents are subcutaneous. Dosing is 3 mg/kg for 20-50 minutes once per month.
6. Defitelio® (defibrotide, Jazz Pharmaceuticals®)
After an initial rejection in 2011, this medication has now been approved to treat severe hepatic veno-occlusive disease. Following stem cell transplants and presenting with blocked veins in the liver, this condition is often fatal. Patients that have renal or pulmonary dysfunction after stem cell transplantation can also use this medication. The mechanism is still unclear, although it is thought that enhanced enzymatic activity of plasmin breaks clots to help improve organ function. Dosing is intravenous and weight based (6.5 mg/kg), requiring administration every 6 hours for 21-60 days.
7. Epclusa® (sofosbuvir/velpatasvir, Gilead®)
This is a massive step in the treatment of hepatitis C: Epclusa® is the first agent to treat all 6 genotypes. Patients with compensated cirrhosis can use this treatment as monotherapy while more progressive disease uses ribavirin adjunctively. Monotherapy for 12 and 24 weeks resulted in sustained virologic response (SVR) rates of 83% and 86%, respectively, while another cohort added ribavirin and the SVR was increased to 94% after only 12 weeks. Tablets contain 400 mg of sofosbuvir and 100 mg of velpatasvir and one tablet is usually taken daily without any required dosage adjustments.
8. Eucrisa® (crisaborole, Pfizer®)
Approved with only a couple weeks left in 2016, this medication is the first to be approved for eczema in the last 15 years. Carrying an indication for mild-to-moderate presentations of the condition, it will be eligible to treat 90% of eczema patients. All signs of eczema were improved after 28 days of therapy in 2 randomized, placebo-controlled studies. The mechanism specific to the disease state is not clear, but Eucrisa® functions as a phosphodiesterase 4 (PDE-4) inhibitor to increase intracellular cyclic adenosine monophosphate. As a topical agent, it is a 2% formulation directed to be applied twice daily.
9. Exondys 51® (eteplirsen, Sarepta Therapeutics®)
A heavily-contested approval within the FDA, this medication was approved without clinical data and only with the notion that a biomarker for Duchenne muscular dystrophy (dystrophin) is increased. The price point of $300,000 per patient-year is under fire considering the lacking data but may be justifiable considering the orphan drug designation. The medication binds to exon 51 on dystrophin mRNA so that, during processing, an internally truncated dystrophin is produced. Once weekly, intravenous, weight-based (30 mg/kg) dosing is administered over 35-60 minutes.
10. Lartruvo® (olaratumab, Eli Lilly®)
Soft tissue sarcomas have the potential to affect many different organ systems. It comes as a relief that these patients have a new treatment for those tumors that cannot be relieved by surgery or radiation. Approved in combination with doxorubicin and in tumors for which anthracycline is an appropriate treatment, Lartruvo® is the first agent approved for initial soft tissue sarcoma treatment in approximately 40 years. The combination therapy improved medial overall survival and progression-free survival compared to doxorubicin alone. By blocking the IgG1 monoclonal antibody, the platelet-derived growth factor receptor-alpha signaling pathway will be disrupted. Administration occurs on days 1 and 8 of a 21-day cycle over an hour in 15 mg/kg intravenous doses.
11. Netspot® (gallium Ga 68 dotatate, Advanced Accelerator Applications®)
This is a nontraditional medication and the second tumor-imaging agent on this list. The sterile, single-dose kit for gallium Ga 68 dotatate injection is specifically to diagnose neuroendocrine tumors (NETs), which may otherwise go undetected for years. Binding occurs at somatostatin receptors to replace somatostatin and signal cancer activity during PET-scans.
12. Nuplazid® (pimavanserin, Acadia®)
Instead of the typical dopamine-focused anti-Parkinson’s agent, this medication targets serotonin-2A receptors. While it is indicated for hallucinations and delusions in Parkinson’s disease, studies are continuing in Alzheimer’s patients. Proper attention should be directed to the black box warning: increased risk of death is noted in elderly patients with dementia-related psychosis. The trial confirming approval was only 6 weeks but did significantly decrease hallucinations and/or delusions compared to placebo. The usual dose is 2, 17 mg tablets taken once daily.
13. Ocaliva® (obeticholic acid, Intercept Pharmaceuticals®)
Ocaliva® is used in combination with ursodeoxycholic acid to treat primary biliary cholangitis. The addition of obeticholic acid is appropriate after 1 year of ursodeoxycholic acid while monotherapy of Ocaliva® is an option if the combination is not tolerated. This may just be the start for this agent as future indications are expected to include non-alcoholic fatty liver disease, or NASH. Targeting the farnesoid X receptor as an agonist, bile acid synthesis is depressed and circulating bile acid is transported out of liver cells. Dosing starts at 5 mg daily but can be increased to 10 mg, with tablets being available in both doses, if clinical results are not satisfactory after 3 months.
14. Rubraca® (rucaparib, Clovis Oncology®)
With 15-20% of all ovarian cancers having the breast cancer susceptibility gene (BRCA) mutation, there is a clear need for agents proven to treat this cancer type. Although 2 or more chemotherapies must have been trialed before initiation of Rubraca®, an FDA-approved companion diagnostic test is available for this agent. The agent works through inhibiting poly ADP-ribose polymerase (PARP) to cause DNA damage, apoptosis, and cell death to tumors. Tablets are 600 mg and should be taken twice daily, with or without food.
15. Spinraza® (Nusinersen, Biogen® & Ionis®)
After orphan drug and fast-track designations and wrapped up with a priority review, Spinraza® was approved for an oft-fatal condition affecting one in 10,000 babies: spinal muscular atrophy. The condition operates through suppressing the production of the survival motor neuron (SMN) protein. This is countered by the medication as it amplifies production of the SMN2 gene to increase production of the SMN protein. Intrathecal dosing is applied for a 12 mg dose every 14 days for the first 3 doses. A fourth dose of 12 mg is administered 30 days after the final loading dose and maintenance dosing is 12 mg every 3 months from that point.
16. Taltz® (ixekizumab, Eli Lilly®)
With other company pipelines still attempting to get their psoriasis agents to market, Lilly successfully launched to get ahead of some of the competition. Taltz® is indicated for moderate-to-severe plaque psoriasis in patients eligible for systemic therapy or phototherapy. The UNCOVER-2 and -3 trials tested ixekizumab against placebo and etanercept and found that administration every 2 or 4 weeks significantly improved established Psoriasis Area and Severity Index (PASI) and static Physician Global Assessment (sPGA) endpoints. A humanized IgG4 monoclonal antibody that inhibits proinflammatory cytokine and chemokine release, subcutaneous loading doses of 160 mg are followed by 80 mg biweekly through week 10 then 80 mg monthly.
17. Tecentriq® (atezolizumab, Roche®)
Along with an original indication for a specific type of bladder cancer called urothelial carcinoma, other indications include non-small cell lung cancer and an orphan drug designation for small cell lung cancer. The first-ever programmed death-ligand 1 (PD-L1) blocking agent interferes with receptors on T cells and antigen-presenting cells to allow the immune system to more appropriately fight tumors. With an initial intravenous dose of 1200 mg over 60 minutes, future doses can be administered over 30 minutes every 3 weeks.
18. Venclexta® (venetoclax, AbbVie® & Roche®)
This medication is the first approved by the FDA to target the B-cell lymphoma 2 (BCL-2) protein and garnered attention as it was able to snag 3 separate breakthrough designations. Currently approved only for chronic lymphocytic lymphoma (CLL) with a chromosome abnormality, indications are expected for relapsed/refractory CLL and combination therapy for untreated acute myeloid leukemia. Through binding the BCL-2 protein, mitochondrial outer membrane activity is triggered and caspases are activated to restore apoptosis.
19. Xiidra® (lifitigrast, Shire®)
Xiidra® has introduced direct competition to Restasis®, and both companies have applied celebrity figureheads, Jennifer Aniston and Marisa Tomei, respectively, to carry out their marketing battle. Carrying an indication for dry eye disease, 4 studies found a larger reduction in eye dryness score (EDS) with lifitegrast at six and 12 weeks. In two of the four studies, an improvement in EDS was seen with lifitegrast at 2 weeks. At week 12, a larger reduction in inferior corneal staining score (ICSS) favoring lifitegrast was observed in 3 of the 4 studies. Lifitigrast blocks an interaction between lymphocyte function-associated antigen-1 and intercellular adhesion molecule-1 which is thought to prevent T cell activation and migration. Optimal dosing is 1 drop in each eye twice daily.
20. Zepatier® (elbasvir/grazoprevir, Merck & Co.®)
With strong competition in the hepatitis C market from Gilead®, Zepatier® will have to rely on decreased wholesale prices and widespread discount provision. Approved for genotypes 1 and 4, along with HIV-1 coinfected patients, sustained virologic response rates ranged from 94-100% in clinical trials. Elbasvir inhibits viral RNA replication and virion assembly through nonstructural protein 5A (NS5A) inhibition; simultaneously, grazoprevir inhibits NS3/4A protease to suppress cleavage of polyproteins used for viral replication. The typical dose is 1 tablet (50 mg elbasvir — 100 mg grazoprevir) once daily for 12-16 weeks.
21. Zinbryta® (daclizumab, Biogen® & AbbVie®)
As this approval carries a boxed warning for liver injury and immune conditions, rendering the medication as part of the Risk Evaluation and Mitigation Strategy (REMS) system, expectations are not high for this relapsing multiple sclerosis treatment. Separate randomized trials, testing monotherapy against placebo and interferon beta-1a, showed statistical significance in the decrease of annualized relapse rate. The mechanism is the first of its kind: a monoclonal antibody targeting interleukin-2 receptor subunits (CD25) that are specific to T cells expressed in patients with multiple sclerosis. Dosing is only once per month, given as a 150 mg subcutaneous injection.
22. Zinplava® (Bezlotoxumab, Merck®)
Once initial shortcomings were surpassed, namely the lacking size of clinical trials, this supplementary Clostridium difficile agent was approved for the market. Although only to be used in conjunction with other antimicrobials, the idea of using this medication is that it will decrease the risk of recurrent C. difficile. Randomized, 12-week studies with more than 1,600 patients observed more sustained clinical response and lower rates of disease recurrence when Zinplava® was compared to placebo. This medication binds toxin B directly to inhibit its function in the human body. Single-dose, intravenous administration is employed at 10 mg/kg over 1 hour.
1. Hirschler B. New drug approvals fall to 6-year low in 2016. Reuters. http://www.reuters.com/article/us-pharmaceuticals-approvals-idUSKBN14M08R. Published January 2, 2017. Accessed January 17, 2017.
2. Various Drug Monographs. Martindale— The Complete Drug Reference. Micromedex 2.0 [database online]. Greenwood Village, CO; Truven Health Analytics; 2017. Accessed January 12-26, 2017.
3. Idrus AA. New drug approvals took a nosedive in 2016. Here are the 22 that made the grade. FierceBiotech. http://www.fiercebiotech.com/special-report/new-drug-approvals-took-a-nosedive-2016-here-are-22-made-grade. Published January 9, 2017. Accessed January 12, 2017.