Top 10 Orphan Drugs in the Late-Stage Pipeline

Promising treatments head for potential FDA approval

Orphan drugs have been in the spotlight recently for reaping hefty profits from tiny patient populations. Some major new prospects are coming down the late-stage pipeline. An article in Endpoint News highlights the top 10 orphan drugs headed for potential FDA approval.

  • Acalabrutinib (AstraZeneca)

Acalabrutinib is a second-generation selective inhibitor of Bruton’s tyrosine kinase. AstraZeneca may be looking to position acalabrutinib as a competitor to venetoclax (Venclexta, AbbVie/Genentech) for the treatment of patients with chronic lymphocytic leukemia.

  • Axicabtagene Ciloleucel (Kite Pharma)

Axicabtagene is a chimeric antigen receptor T-cell (CAR-T) treatment for patients with aggressive, chemorefractory B-cell non-Hodgkin’s lymphoma. In a recent study, 41% of patients achieved a positive tumor response at six months after a single infusion, and 36% percent were in complete remission.

  • CTL019 (Novartis)

CTL019 is a CAR-T treatment for pediatric patients with leukemia. In a global phase 2 trial, 82% (41/50) of pediatric patients achieved complete or partial remission.

  • Deutetrabenazine (SD-809, Teva)

The FDA recently granted priority review for deutetrabenazine (SD-809), an oral, small- molecule vesicular monoamine 2 transporter (VMAT2) inhibitor, for the treatment of patients with tardive dyskinesia. The compound was previously rejected for use in Huntington’s chorea.

  • Emicizumab (Roche)

Emicizumab is a bispecific antibody designed to bind factors IXa and X, replacing the function of missing factor VIII, in patients with hemophilia.

  • Lanadelumab (Shire)

Lanadelumab is a human monoclonal antibody designed to prevent angioedema in patients with the hereditary form of the disease. In clinical trials, the drug reduced angioedema rates by 88%.

  • LentiGlobin (Bluebird Bio) 

LentiGlobin is gene therapy for patients with sickle cell anemia or beta-thalassemia major.

  • Niraprib (Tesaro, Inc.)

Niraparib is a poly ADP ribose polymerase (PARP) enzyme inhibitor for patients with ovarian cancer. In a clinical trial involving 553 patients, those with the BRCA gene experienced 21 months of progression free survival (PFS)—15 months longer than that of the control group. In addition, patients in the non-germline BRCA mutant cohort showed PFS of 9.3 months compared with 3.9 months for control.

  • Tremelimumab (AstraZeneca)

Tremelimumab is a checkpoint inhibitor designed to be administered with durvalumab in patients with head-and-neck squamous cell carcinoma. The treatment inhibits the activity of cytotoxic T-lymphocyte–associated antigen-4 (prCTLA-4), thereby boosting the immune response against cancer cells.

  • Veliparib (AbbVie)

Veliparib, a PARP enzyme inhibitor, received an orphan drug designation from the FDA in November 2016. The compound is being investigated in combination with chemotherapy, such as carboplatin or paclitaxel, or radiotherapy for the treatment of patients with advanced squamous non–small-cell lung cancer (NSCLC).

Sources: Endpoint News; March 1, 2017; and BioSpace; March 2, 2017.