The year 2018 reflects the continued growth in new drug approvals by the FDA that has been seen over the past few years. As the FDA has implemented new programs to streamline its review and approval processes, a total of 55 novel drugs were approved between January 1 and December 1, 2018.1 Of these, 16 new drugs had indications in oncology, hematology, or supportive care.
Here we highlight some of the notable approvals of first-in-class drugs, novel drugs for areas otherwise lacking in therapy options, new indications for drugs previously approved by the FDA, and biosimilar drugs that happened in 2018.
First-in-Class Drug Approvals
Several new drugs that were approved this year represented first-in-class products.
The approval of lutetium Lu 177 dotatate (Lutathera) for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors marks the first approved peptide receptor radionuclide therapy.2
Ivosidenib (Tibsovo), an IDH1 inhibitor, was approved for use in adults with relapsed or refractory acute myeloid leukemia (AML) who have specific mutations in the IDH1 gene are eligible for treatment with ivosidenib. The FDA approved ivosidenib for use with the RealTime IDH1 assay, an FDA-approved companion diagnostic used to detect IDH1 mutations in blood or bone marrow samples.
Duvelisib (Copiktra), an oral inhibitor of PI3K, is the first approved dual inhibitor of PI3K-δ and PI3K-γ. It was approved this year for the treatment of adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma who have received at least 2 previous therapies.
Venetoclax (Venclexta) was approved for the treatment of pretreated patients with CLL who have a 17p deletion, as well as in combination with azacytidine, decitabine, or low-dose cytarabine for newly diagnosed AML in adults who are either aged ≥75 years or who have comorbidities that preclude use of intensive induction chemotherapy.
The approval of moxetumomab pasudotox-tdfk (Lumoxiti) marked the first approved drug for hairy cell leukemia in >20 years. The FDA approved moxetumomab pasudotox-tdfk injection for intravenous use for the treatment of adults with relapsed or refractory hairy cell leukemia who have received at least 2 prior systemic therapies, including treatment with a purine nucleoside analog.3
Larotrectinib (Vitrakvi) was approved for the treatment for adult and pediatric patients with an NTRK gene fusion who have metastatic cancer, for whom surgical resection is likely to result in severe morbidity and no satisfactory alternative treatments exist, or whose cancer has progressed following treatment.
First Agents Approved in Their Indications
Some novel drugs offered treatment options for patients with cancers that had previously been untreatable, or for which few treatment options existed.
Cemiplimab-rwlc (Libtayo) was approved for use in patients with metastatic or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or radiation.
Another new drug that filled an unmet need was mogamulizumab-kpkc (Poteligeo), which represented the first FDA approved drug specifically for Sézary syndrome (SS). Mogamulizumab-kpkc is indicated for intravenous use for the treatment of adults with relapsed or refractory mycosis fungoides or pretreated SS.
Iobenguane I 131 (Azedra) is the first FDA-approved intravenous drug for the treatment of adults and adolescents aged ≥12 with rare tumors of the adrenal gland (pheochromocytoma or paraganglioma) that are unresectable, metastatic, and require systemic anticancer therapy.
Apalutamide (Erleada) was the first FDA-approved treatment for nonmetastatic, castration-resistant prostate cancer.4
Notably, glasdegib (Daurismo) received approval for use in combination with low-dose cytarabine in newly diagnosed patients with AML who are aged ≥75 years or who have comorbidities that preclude intensive induction chemotherapy. Although it is not the first agent approved for this indication, glasdegib is the first and only FDA-approved Hedgehog pathway inhibitor for AML.
New Uses for Previously Approved Therapies
One continuing trend this past year has been the approval of new indications for drugs already approved by the FDA.
Olaparib (Lynparza) was approved for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative, metastatic breast cancer who received chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.5
Talazoparib (Talzenna) was another drug approved for the treatment of patients with germline BRCA-mutated, HER2-negative, locally advanced or metastatic breast cancer.
Brentuximab vedotin (Adcetris) received approval in combination with chemotherapy for the treatment of previously untreated systemic anaplastic large-cell lymphoma or other CD30-expressing peripheral T-cell lymphomas.
The combined use of dabrafenib (Tafinlar) and trametinib (Mekinist) is now approved for the treatment of unresectable or metastatic BRAF V600E mutation-positive anaplastic thyroid cancer.
Blinatumomab (Blincyto) is now indicated to treat adults and children with B-cell precursor acute lymphoblastic leukemia who are in remission but still have minimal residual disease.
New Uses for Immunotherapies in Oncology
The year 2018 also saw expanded indications for immunotherapies already approved by the FDA.
Nivolumab (Opdivo) received expanded approval for the treatment of patients with metastatic small-cell lung cancer that progressed after platinum-based chemotherapy and at least 1 other line of therapy, and in combination with ipilimumab (Yervoy) for the treatment of intermediate-or poor-risk, previously untreated advanced renal cell carcinoma.6
The FDA updated the indications for pembrolizumab (Keytruda) and atezolizumab (Tecentriq) to include patients with locally advanced or metastatic urothelial cancer who are cisplatin-ineligible to require the use of an FDA-approved companion diagnostic test to determine PD-L1 levels in tumor tissue.7
The FDA brought the total number of approved indications for pembrolizumab up to 14 this year. Among the novel indications added were recurrent or metastatic cervical cancer with PD-L1–expressing tumors that progressed during or after chemotherapy8; relapsed or refractory primary mediastinal large B-cell lymphoma; and previously treated hepatocellular carcinoma.9
Pembrolizumab is now also approved in combination with pemetrexed and platinum-based chemotherapy for the first-line treatment of patients with metastatic, nonsquamous non–small-cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations,10 and in combination with carboplatin and paclitaxel or nab-paclitaxel for the first-line treatment of metastatic, squamous NSCLC, regardless of PD-L1 expression.11
In addition, durvalumab (Imfinzi), a PD-L1 inhibitor that was approved in 2017 for the treatment of certain patients with locally advanced or metastatic bladder cancer, is now approved for use in patients with stage III NSCLC whose tumors are unresectable and whose cancer has not progressed after treatment with chemotherapy and radiation.12
New Biosimilars for Oncology Supportive Care
The FDA approved a handful of new biosimilar drugs this year, many of which are indicated for use in patients with cancer, including:
• Retacrit (epoetin alfa-epbx) as a biosimilar to Epogen/Procrit (epoetin alfa; Amgen) for the treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy
• Fulphila (pegfilgrastim-jmdb) and Udenyca (pegfilgrastim-cbqv) as biosimilars to Neulasta (pegfilgrastim; Amgen) to decrease the chance of infection as suggested by febrile neutropenia in patients with nonmyeloid cancer who are receiving myelosuppressive chemotherapy
• Nivestym (filgrastim-aafi) as a biosimilar to Neupogen (filgrastim; Amgen) for all eligible indications of the reference drug.
See ‘Biosimilar Drugs in Oncology: What Has the FDA Approved So Far?’ for a full rundown of these and other oncology and oncology supportive biosimilars that have been approved by the FDA to date.
