Looking Ahead: New Drug Approvals for 2017
Will New Drug Approvals Rebound in 2017?
The number of novel agents approved by the FDA in 2016 fell to a six-year low when compared to the booming previous few years. In fact, when looking at new drug approvals overall, the numbers declined by close to 50%.
Should the world of pharma be worried? Probably not. The differences may be short-lived and are attributed to fewer submitted new drug applications (NDAs), more "complete response letters" - FDA lingo for an application rejection in its current form - and five expected 2016 approvals getting bumped into 2017.2017 may be looking a bit more rosy: according to the FDA’s Office of New Drugs, 36 new molecular entity NDAs were received by FDA through mid-December 2016, already beating the average number of 35 for the past decade. Here's a few to look out for in the coming months.
Binimetinib (MEK162) for Melanoma
Melanoma is a top 10 cancer in the US, with over 10,000 deaths from the disease projected in 2016. Binimetinib from Array BioPharma is a late-stage, oral, small-molecule MEK inhibitor previously under investigation for the monotherapy treatment of advanced NRAS-mutant melanoma (skin cancer). However, in March 2017 Array announced that it had withdrawn its binimetinib NDA from the FDA for NRAS-mutant melanoma. Array's discussions with the FDA revealed that the clinical benefit demonstrated in the Phase 3 NEMO clinical trial would not be found sufficient to support approval of the NRAS-mutant melanoma NDA. There are currently no approved therapies specifically targeting NRAS-mutant melanoma.
However, this does not affect other ongoing clinical trials with binimetinib. MEK is a key enzyme that regulates cell activities, and errors in this pathway can lead to various tumors types. This action will not impact the planned Phase 3 COLUMBUS trial of binimetinib, in combination with encorafenib, for the treatment of BRAF-mutant melanoma, which remains on track for mid-2017. Phase 3 studies in colorectal cancer are also ongoing.
Brigatinib (Alunbrig) for NSCLC
Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for roughly 190,000 new cases each year in the US. However, roughly 3% to 8% of patients with NSCLC have a genetic rearrangement in the anaplastic lymphoma kinase positive (ALK) gene. Brigatinib, an ALK inhibitor, was approved in April 2017 for the treatment of patients with ALK+ NSCLC who have progressed on or are intolerant to crizotinib (Xalkori).
In October 2016 the FDA accepted Ariad's NDA for brigatinib with priority review status. Brigatinib was also granted orphan drug designation in May 2016. In the pivotal Phase 2, open-label ALTA study which enrolled 222 patients, the overall response rate after a median follow up of 8 months at the recommended dosing was 53 to 54 percent, and the median duration of response ranged from 11.1 to 13.8 months. The most common adverse reactions (≥25%) with Alunbrig were nausea, diarrhea, fatigue, cough, and headache. Alunbrig is a once-daily oral therapy that may be taken with or without food.
Durvalumab (Imfinzi) for Bladder Cancer
Urothelial cancer develops in the cells of the bladder lining and is the most common type of bladder cancer, accounting for roughly 90% of cases. Durvalumab (Imfinzi), from AstraZeneca, was FDA-approved in May 2017 for the treatment of patients with advanced urothelial carcinoma (bladder or urinary tract cancer) who have disease progression despite use of platinum-containing chemotherapy with or without surgery.
Imfinzi is an anti-PD-L1 (programmed death ligand-1) human monoclonal antibody in the same class of drugs as Tecentriq (atezolizumab) and Bavencio (avelumab), also approved for advanced urothelial carcinoma. By inhibiting PD-L1, these agents help increase T-cell activity against the cancer to counteract efforts to evade the immune system.
In studies, Imfinzi had an objective response rate (ORR) of 17%, regardless of PD-L1 status, with an ORR of 26.3% in patients with PD-L1 high-expressing tumors. Among 31 patients who responded to treatment, 14 patients (45%) had ongoing responses of at least 6 months and 5 patients (16%) at least 12 months. Of all evaluable patients, 2.7% achieved complete response.
Dupilumab (Dupixent) for Atopic Dermatitis
Three Phase 3 pivotal studies were submitted to the FDA in support of the BLA; two as monotherapy and one in combination with topical corticosteroids for atopic dermatitis. Dupilumab, the first in a new class of immunotherapies, inhibits signaling of cytokines IL-4 and IL-13, required for the type 2 immune response.
As monotherapy in the SOLO 1 and SOLO 2 trials, dupilumab significantly improved atopic dermatitis symptoms including pruritus (itching), symptoms of anxiety and depression, and quality of life, as compared with placebo. Dupilumab is under study for asthma as another important indication.
Romosozumab (Evenity) for Osteoporosis
Romosozumab, from Amgen/UCB, is an anti-sclerostin monoclonal antibody under study for the treatment of osteoporosis in postmenopausal women at increased risk of fracture, as well as men aged 55-90 years with osteoporosis and risk for fracture. Romosozumab works by binding and inhibiting the activity of the protein sclerostin, yielding a dual effect on bone by both increasing bone formation and decreasing bone breakdown.
In Phase 3 FRAME studies, over 7,000 women were randomly assigned to receive a monthly subcutaneous 210 mg dose of romosozumab or placebo. The study revealed a statistically significant 73 percent reduction in the relative risk of a new vertebral (spine) fracture through 12 months, compared to those receiving placebo.
In July 2017, Amgen/UCB received a Complete Repsonse Letter from the FDA requesting the addition of data (with resubmission of the application) from the Phase 3 active-comparator ARCH study with alendronate. In addition, the efficacy and safety data from the BRIDGE study and the Phase 3 trial evaluating Evenity in men with osteoporosis were requested to be added. All together, these 3 pivotal romosozumab studies represent data from more than 11,000 patients.
Ocrelizumab for Multiple Sclerosis
Ocrelizumab (Ocrevus) from Genentech/Roche is a humanized monoclonal antibody now approved for both relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS) forms. Ocrevus is the first medication approved for PPMS, a more advanced form of MS.
Ocrelizumab targets CD20-positive B-cells involved in the inflammation and nerve degeneration in multiple sclerosis. By targeting CD20 cell surface proteins not on stem cells or plasma cells, important functions of the immune system may be preserved, according to the sponsor.
Results from the ORATORIO and OPERA Phase III studies, revealed statistically significant results. In OPERA I and II, the data showed Ocrevus increased the proportion of RMS patients achieving the target endpoint by 75% compared with interferon beta-1a over 96 weeks. In ORATIO, Ocrevus treatment significantly increased the proportion of PPMS patients meeting the target endpoint by 47% at week 120 compared with placebo. The FDA approved ocrelizumab on March 28, 2017.
Drugs.com Approvals Archive
Need to look at other past approvals, whether from 2017 or before? You can access the Drugs.com Approvals Archive for a full historical overview back to 2002.
Review FDA documents, manufacturer press releases on clinical studies, and timelines involved with approval of these new agents. See new drugs, study results, newly approved indications, as well as first-time generics that have cleared the FDA.
You can also access links to more closely review the medical conditions for upcoming approvals and stay on top of the ever-growing pipeline of novel therapeutic agents traversing the halls at the FDA.
Finished: Looking Ahead: New Drug Approvals for 2017
- Amgen and UCB Receive Complete Response Letter from U.S. FDA for Evenity (romosozumab) BLA. New Drug Applications. Drugs.com. Accessed July 31, 2017 at https://www.drugs.com/nda/evenity_170716.html
- Callener C. FDA New Drug Approvals Down Significantly in 2016. PharmTech.com. Accessed January 15, 2017 at http://www.pharmtech.com/fda-new-drug-approvals-down-significantly-2016
- Simpson EL, et al. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med 2016; 375:2335-48. Accessed January 16, 2017 at http://www.nejm.org/doi/full/10.1056/NEJMoa1610020
- Montalban Z, et al. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. NEJM. December 21, 2016. Accessed January 17, 2017 at http://www.nejm.org/doi/full/10.1056/NEJMoa1606468#t=article
- Hauser SL, et al. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. NEJM. December 21, 2016. Accessed January 17, 2017 at http://www.nejm.org/doi/full/10.1056/NEJMoa1601277