Specialty Drug Approvals Monthly Update: December 2023

This monthly approvals wrap-up provides a review of newly approved specialty drugs, recent drug launches, generic updates, new indications and news of note on drugs in the approval process.

See separate article for approval information on traditional drugs.

New Drugs

Ogsiveo™ (nirogacestat): The United States (U.S.) Food and Drug Administration (FDA) approved Ogsiveo under a Priority Review and Real-Time Oncology Review. Ogsiveo is an oral gamma secretase inhibitor indicated for adults with progressing desmoid tumors who require systemic treatment. Ogsiveo is approved as oral tablets for twice daily dosing that is continued until disease progression or unacceptable toxicity occurs. In the double-blind, phase 3 DeFi (NCT03785964) trial, Ogsiveo demonstrated a statistically significant 71% reduction compared to placebo in the primary endpoint of progression-free survival (PFS) (p< 0.001).¹ The median PFS was not reached in the Ogsiveo arm and was 15.1 months in the placebo arm. In addition, the objective response rate (ORR) was significantly higher with Ogsiveo compared with placebo (41% versus 8%, respectively; p<0.001), with complete response rates of 7% and 0%, respectively. Ogsiveo was granted Breakthrough Therapy, Fast Track, and Orphan Drug designations by the FDA. The agent is available in the U.S. through a specialty pharmacy and distributor network. During an investor call, it was announced that a 30-day supply will have a wholesale acquisition cost (WAC) of $29,000.

Alvaiz™ (eltrombopag choline): Teva’s Alvaiz, a thrombopoietin receptor agonist, was FDA approved for the treatment of certain forms of thrombocytopenia and severe aplastic anemia. Alvaiz was approved through the 505(b)(2) pathway using Novartis’ Promacta® (eltrombopag) as the reference drug.

Phyrago™ (dasatinib): Phyrago, by Nanocopoeia, was approved under a 505b2 NDA using the reference product Sprycel®(dasatinib). Phyrago is indicated for the treatment of adults with: newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase; chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. It is approved as 20 mg, 50 mg, 70 mg, 80 mg, 100 mg, and 140 mg oral tablets, for once daily dosing. Unlike Sprycel by Bristol-Myers Squibb (BMS), Phyrago is not approved for use in pediatric patients with newly diagnosed Ph+ ALL. The Phyrago labeling states that due to BMS’s marketing exclusivity rights, the drug product is not labeled with pediatric information. Both products are approved in the same tablet strengths.

Casgevy™ (exagamglogene autotemcel): The FDA approved Casgevy by Vertex. It is one of two cell-based gene therapies recently approved for the treatment of sickle cell disease (SCD) in patients ≥ 12 years of age with recurrent vaso-occlusive events (VOEs). Casgevy is the first gene therapy to utilize CRISPR-based technology to alter a patient’s hematopoietic stem cells (HSCs) to produce red blood cells (RBCs) with high levels of fetal hemoglobin (HbF). Casgevy is intended to be used as a 1-time intravenous (IV) infusion that is administered at authorized treatment centers. Treatment involves mobilization, collection, and editing of the patients HSCs, as well as myeloablative conditioning therapy prior to re-introduction of the engineered HSCs back into the patient. The open-label, phase 1/2/3 CLIMB-SCD-121 (NCT03745287) study enrolled patients with a history of ≥ 2 severe VOEs during each of the 2 years prior to screening.² Interim data revealed that, at a median follow-up of 22.2 months, 29 of the 31 (93.5%) patients who received 1 dose of Casgevy did not experience any protocol-defined VOEs for ≥ 12 consecutive months within the first 24 months after the dose (primary endpoint). Treatment-emergent adverse effects included stomatitis, pancytopenia, and febrile neutropenia. The FDA granted Casgevy Fast Track, Orphan Drug, Rare Pediatric Diseases, and Regenerative Medicines Advanced Therapy designations as well as a Priority review. Vertex announced a 1-time WAC of $2.2 million per patient. Casgevy is also being reviewed by the FDA for transfusion-dependent beta-thalassemia, with a decision expected by March 20, 2024.

Lyfgenia™ (lovotibeglogene autotemcel): The FDA also approved the cell-based gene therapy Lyfgenia, by Bluebird Bio, for the treatment of SCD in patients ≥ 12 years of age with a history of VOEs. Lyfgenia is intended as a 1-time IV infusion to be administered at qualified treatment centers. Treatment involves mobilization, collection, and editing of the patients HSCs, and myeloablative conditioning before the patient receives the dose of the engineered HSCs. Lyfgenia’s open-label, phase 3 HGB-210 (NCT04293185) trial enrolled patients with a history of ≥ 4 VOEs in the previous 24 months.³ The efficacy outcomes were complete resolution of VOEs (VOE-CR) and severe VOEs (sVOE-CR) between 6 months and 18 months after the Lyfgenia infusion. Among 36 patients evaluated, these outcomes occurred in 28 and 30 patients, respectively, translating to a 88% rate of complete resolution of VOEs and 94% response rate against severe VOEs. Adverse effects associated with the treatment regimen included stomatitis, pancytopenia, and febrile neutropenia. Lyfgenia also carries a boxed warning regarding an increased risk of hematologic malignancy; patients should receive lifelong monitoring. Lyfgenia was granted Fast Track, Orphan Drug, Rare Pediatric Diseases, and Regenerative Medicines Advanced Therapy designations and a Priority review by the FDA. Bluebird bio announced a one-time WAC of $3.1 million for Lyfgenia.

Iwilfin™ (eflornithine): US WorldMeds received FDA approval for their ornithine decarboxylase inhibitor, Iwilfin, to reduce the risk of relapse of high-risk neuroblastoma (HRNB) in adult and pediatric patients with at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy. This is the first FDA approved therapy intended to reduce the risk of relapse in pediatric patients with HRNB. Iwilfin is approved as oral tablets, with a recommended dosage based on the patient’s body surface area. Doses are administered twice daily until disease progression, unacceptable toxicity, or a maximum of 2 years. Iwilfin can cause hearing loss, myelosuppression and hepatotoxicity, so baseline audiogram, complete blood count (CBC), and liver function tests should be performed prior to starting therapy. In the phase 2 clinical trials, the primary analysis included 90 patients treated with Iwilfin and 270 control patients.⁴ Patients were followed for a total of 7 years after completion of Iwilfin therapy. In the primary analysis, the primary endpoint of event-free survival demonstrated a hazard ratio (HR) of 0.48. An overall survival HR of 0.32 was also reported. Launch of Iwilfin is planned within weeks of the FDA approval, with pricing information to follow.

Alyglo™ (immune globulin intravenous, human-stwk) 10% liquid: GC Biopharma received FDA approval for Alyglo for the treatment of primary humoral immunodeficiency (PHI) in individuals 17 years and older. The recommended dosage is 300 to 800 mg/kg IV every 3 to 4 weeks. In a single-arm clinical trial, during the 12-month study period, the primary endpoint of acute serious bacterial infections (SBIs) rate was 0.03.⁵ This met the predefined success rate of < 1 acute SBI per patient per year. All immune globulin (IV and SC) products carry a boxed warning regarding the risk of thrombosis. Some data suggests that the presence of residual activated FXIa in commercial IV immune globulin products may be associated with thromboembolic events.⁶ Alyglo is made using cation exchange chromatography (CEX), which removes coagulation factor XIa from the product. Launch timeframe of Alyglo has yet to be announced, with pricing information to follow.

New Biosimilars

Avzivi® (bevacizumab-tnjn): The FDA approved Avzivi by Biothera, a new biosimilar to Avastin® (bevacizumab). Avziv carries the following indications that are consistent with the reference product: metastatic colorectal cancer; first-line for non-squamous non-small cell lung cancer; recurrent glioblastoma; metastatic renal cell carcinoma, persistent; recurrent, or metastatic cervical cancer; and epithelial, ovarian, fallopian tube, or primary peritoneal cancer. Avzivi is not indicated for hepatocellular carcinoma or for all the indications for epithelial, ovarian, fallopian tube, or primary peritoneal cancer as Avastin. Like Avastin, Avzivi is approved as a 100 mg/4 mL and 400 mg/16 mL solution in an single-dose vial for IV administration by healthcare professional (HCP). Biosimilarity was based on a phase 1 pharmacokinetics study and a phase 3 efficacy, safety, and immunogenicity study in patients with advanced non-small cell lung cancer that compared Avzivi with Avastin.⁷ Avzivi is the fifth biosimilar for Avastin approved in the U.S.; none are considered by the FDA to be interchangeable products to Avastin. Sandoz will commercialize Avzivi in the U.S. The launch timeframe has not been announced. Pricing will follow.

New Indications

Jaypirca® (pirtobrutinib): The FDA approved the oral Bruton tyrosine kinase (BTK) inhibitor, Jaypirca, for the treatment of adults with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received ≥ 2 prior lines of therapy, including a BTK inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication was approved under an Accelerated Approval based on response rate and its continued approval may depend upon results from a confirmatory trial. In a single-arm study, Jaypirca demonstrated a 72% objective response rate (ORR) and a median duration of response (DOR) of 12.2 months in patients with CLL/SLL who met criteria of the new indication.⁸

Wilate® (von Willebrand factor/coagulation factor VIII complex (human): The FDA expanded the indication for Wilate, by Octapharma, for von Willebrand disease (VWD) to include routine prophylaxis to reduce the frequency of bleeding episodes in adult and pediatric patients ≥ 6 years of age with VWD. Wilate is the first von Willebrand factor concentrate indicated for prophylactic treatment pf VWD. Wilate was already approved for on-demand treatment and perioperative management of bleeding in adults and pediatric patients with VWD.  For routine prophylaxis of VWD, Wilate is administered IV by an HCP 2 or 3 times per week, with exact dosing based on VWD severity and the patient’s clinical status and response to therapy.⁹

Adbry® (tralokinumab-idrm): The FDA expanded AstraZeneca/MedImmune/Leo Pharma’s Adbry to include pediatric patients aged 12 to 17 years with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Previously, the atopic dermatitis indication only included adults.

Welireg® (belzutifan): Welireg, an oral a hypoxia-inducible factor inhibitor by Merck, received a new indication for the treatment of adults with advanced renal cell carcinoma (RCC) following a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI).

Padcev® (enfortumab vedotin-ejfv): Pfizer/Astellas received FDA approval for Padcev to be used in combination with Merck’s Keytruda® (pembrolizumab) for patients with locally advanced or metastatic urothelial cancer.

Bivigam® (IV immune globulin 10%): ADMA Biologics received an expanded indication for Bivigam for the primary humoral immunodeficiency (PHI) indication to include pediatric patients ≥ 2 years of age. The recommended dosage in adults and pediatric patients is the same, 300 to 800 mg/kg IV every 3 to 4 weeks and may be adjusted to achieve the desired trough levels and clinical response.¹⁰