Nov. 20, 2024 - zanidatamab-hrii (Ziihera)  

The FDA has granted Accelerated Approval to the bispecific human epidermal growth factor receptor (HER)2-directed antibody Ziihera from Jazz. The agent received approval for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) biliary tract cancer (BTC), as detected by an FDA-approved test. The Accelerated Approval was granted based on overall response rate (ORR) and duration of response (DOR); therefore, continued approval for this use may require demonstration of benefit in confirmatory clinical trial(s). Patients should be selected for treatment based on the presence of HER2-positive (IHC 3+) tumor specimens, as detected by an FDA-approved test. The Ventana Pathway anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody has received FDA approval for this use as the companion diagnostic device for identification of eligible patients. Ziihera is supplied as a lyophilized powder in a single-dose vial in the strength of 300 mg. Dosing is based on the patient’s body weight, and the product is given as an intravenous (IV) infusion once every two weeks by a health care professional (HCP), with therapy continued until disease progression or unacceptable toxicity. Patients should receive premedication with acetaminophen, an antihistamine (e.g., diphenhydramine), and a corticosteroid (e.g., hydrocortisone) 30 to 60 minutes before each infusion to prevent infusion-related reactions. Infusions are administered over 60 to 150 minutes depending on the infusion number (earlier infusions have longer durations) and tolerability. Approval was based on the open-label, single-arm, phase 2b, HERIZON-BTC-01 clinical trial (n=62), which demonstrated an ORR of 52% (95% confidence interval [CI], 39 to 65) with a median DOR of 14.9 months (95% CI, 7.4 to not estimable). Ziihera has been added to the National Comprehensive Cancer Network (NCCN) BTC guidelines as a category 2A option that is useful in certain circumstances for unresectable or metastatic progressive HER2-positive tumors that are IHC3+ in the subsequent-line systemic therapy setting. Other category 2A recommendations in this setting include fam-trastuzumab deruxtecan-nxki (for IHC3+ tumors) (Enhertu), trastuzumab (Herceptin, biosimilars) + pertuzumab (Perjeta), and tucatinib (Tukysa) + trastuzumab. Ziihera was reviewed with Assessment Aid under the Priority Review pathway. It received Breakthrough Therapy and Orphan Drug designations from the FDA. The agent carries a boxed warning for embryo-fetal toxicity. Ziihera is available with an average wholesale price (AWP) of $4,266 per 300 mg vial. 

Nov. 22, 2024 - acoramidis (Attruby) 

BridgeBio’s Attruby has received FDA approval for the treatment of cardiomyopathy of wild-type or variant transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular (CV) death and CV-related hospitalization. This transthyretin (TTR) stabilizer is approved as an oral tablet in the strength of 356 mg and is taken orally twice daily. Approval was based on a randomized, double-blind, placebo-controlled, phase 3 trial (ATTRibute-CM; n=611) that favored Attruby over placebo (p<0.001) for the four-step primary hierarchical outcome evaluating death from any cause, CV-related hospitalization, the change from baseline in the N-terminal pro–B-type natriuretic peptide (NT-proBNP) level, and the change from baseline in the six-minute walk distance. Attruby was reviewed under the Standard Review pathway and received Orphan Drug designation. The TTR stabilizers tafamidis (Vyndamax) and tafamidis meglumine (Vyndaqel) are similarly indicated. The Institute for Clinical and Economic Review (ICER) panel found that current evidence is sufficient to demonstrate a net health benefit for monotherapy with either acoramidis or tafamidis compared to no disease-specific treatment; however, evidence is inadequate to distinguish a net health benefit between these agents when used as monotherapy. Attruby is able to provide near-complete stabilization (> 90% across the entire dosing interval) of TTR, thereby allowing for the normal function of TTR as a transport protein. Attruby is available with an AWP of $22,510.94 per 28-day supply. 

Dec. 4, 2024 – zenocutuzumab-zbco (Bizengri) 

The FDA has granted Accelerated Approval to Merus N.V.’s bispecific HER2- and HER3-directed antibody Bizengri. The agent is indicated (1) for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy and (2) for the treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring an NRG1 gene fusion with disease progression on or after prior systemic therapy. Both indications were based on ORR and DOR; therefore, continued approval for these uses may require demonstration of benefit in confirmatory clinical trial(s). Patients should be selected for treatment based on the presence of an NRG1 gene fusion in tumor specimens. Currently, an FDA-approved companion diagnostic for detection of this gene fusion is not available. Bizengri will be supplied as a solution for injection in a single-dose vial in the strength of 375 mg/18.75 mL (20 mg/mL). The recommended dosage is given every two weeks as an IV infusion over four hours. Therapy with Bizengri is continued until disease progression or unacceptable toxicity. Premedication with a corticosteroid (e.g., dexamethasone), an antipyretic (e.g., acetaminophen) and an H1 antihistamine (e.g., dexchlorpheniramine) is required prior to each infusion to decrease the risk for infusion-related reactions. Left ventricular ejection fraction (LVEF) should be evaluated prior to starting therapy. Approval was based on an open-label, multicohort study (eNRGy; n=64 for NSCLC patients; n=30 for pancreatic adenocarcinoma patients) that demonstrated a 33% ORR (1.6% complete response rate; 31% partial response rate) and median DOR of 7.4 months (95% CI, 4 to 16.6) for NSCLC patients. The ORR for pancreatic adenocarcinoma patients was 40% (3.3% complete response rate, 37% partial response rate) with a DOR range of 3.7 months to 16.6 months. Bizengri is the first FDA-approved systemic therapy for patients with these cancer types harboring an NRG1 gene fusion. Bizengri is expected to be used as a treatment option for patients with progression on or after prior systemic therapy for pancreatic adenocarcinoma or NSCLC with an NRG1 gene fusion. The agent was reviewed under Priority Review utilizing Assessment Aid. It received Breakthrough Therapy and Orphan Drug designations. Bizengri carries a boxed warning for embryo-fetal toxicity. Launch is expected within weeks of approval with pricing to follow.