Dec. 18, 2024 – remestemcel-L-rknd (Ryoncil)

Mesoblast’s Ryoncil has received FDA approval for the treatment of steroid-refractory acute graft-versus-host disease (SR-aGVHD) in pediatric patients ≥ 2 months of age. Ryoncil is an allogeneic (donor) bone marrow-derived mesenchymal stromal cell (MSC) therapy, and its approval marks the first FDA-approved MSC therapy. Product will be supplied as a cell suspension for IV infusion in a target concentration of 6.68 x 10⁶ MSCs per mL in 3.8 mL contained in a 6 mL cryovial. Recommended dosage and infusion rates are based on body weight. Ryoncil is administered under the supervision of an HCP experienced in managing SR-aGVHD. It is given via IV infusion twice per week for four consecutive weeks; infusions should be administered a minimum of three days apart with response assessed 28 days (+/- 2 days) after the first dose to determine further treatment (e.g., complete response=no further treatment with Ryoncil; partial response=repeat administration of Ryoncil once a week for an additional four weeks; no response=consider alternatives). Patients should receive premedication with corticosteroids and antihistamines 30 to 60 minutes prior to administration to decrease infusion reactions. Approval was based on a single-arm, multicenter, prospective, Phase 3 study (MSB-GVHD 001; n=54) that demonstrated the day-28 overall response rate (ORR) was 70.4% which was sustained through day 100 and included an increase in complete responders at day 28 (29.6%) to day 100 (44.4%). Furthermore, overall survival was 74.1% at day 100 and 68.5% at day 180. Ryoncil requires shipping and storage in a liquid nitrogen vapor phase until thawing immediately prior to administration. The MSC therapy was reviewed under the Priority Review pathway and received Fast Track and Orphan Drug designations. According to NCCN, ruxolitinib is the Category 1 suggested systemic therapy agent for steroid-refractory acute GVHD (aGVHD). A range of alternative therapies are also listed as potential options (Category 2A) including monoclonal antibodies (e.g., alemtuzumab, infliximab), extracorporeal photopheresis, and other immunosuppressants (e.g., mycophenolate mofetil, sirolimus); the selected systemic agent is often used in combination with the original immunosuppressive therapy (corticosteroids). Patients enrolled in the study used for approval of Ryoncil were naïve to other immunosuppressant therapies for aGVHD apart from the steroid. Launch time frame for the novel therapy is pending; product will be available at transplant centers and other treating hospitals.  

Dec. 19, 2024 – olezarsen (Tryngolza) 

The FDA has granted approval to Ionis’ apolipoprotein C-III (APOC-III)-directed antisense oligonucleotide, Tryngolza, as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). This first-in-class agent is supplied as 80 mg/0.8 mL in a single-dose autoinjector and is given as a subcutaneous (SC) injection once monthly into the abdomen or front of the thigh when self-administered; the back of the upper arm can also be used an injection site if given by a caregiver or HCP. Approval was based on a double-blind, placebo-controlled, Phase 3 clinical trial (BALANCE; n=66) that demonstrated a significant improvement in the percent change in fasting triglycerides from baseline to month six with olezarsen 80 mg compared to placebo (-43.5%; p<0.001). Patients enrolled in the study were concurrently receiving other lipid lowering therapies (e.g., statins, omega-3 fatty acids, fibrates); however, patients with FCS generally have a minimal response to these conventional therapies. Tryngolza is the first treatment for adults with FCS. The agent was reviewed under Priority Review and received Breakthrough Therapy, Fast Track and Orphan Drug designations. Tryngolza is available and carries an AWP of $59,500.80 per 80 mg/0.8 mL autoinjector.  

Dec. 20, 2024 – concizumab-mtci (Alhemo) 

Novo Nordisk’s Alhemo has received FDA approval for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ≥ 12 years of age with: (1) hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors or (2) hemophilia B (congenital factor IX deficiency) with factor IX inhibitors. This tissue factor pathway inhibitor (TFPI) antagonist will be supplied in single-patient-use prefilled pens in three strengths: 60 mg/1.5 mL, 150 mg/1.5 mL and 300 mg/3 mL. It is administered by SC injection into the abdomen or thigh with daily rotation of injection sites and can be self-administered or administered by a caregiver following appropriate training. A weight-based loading dose is given on day one, followed by once daily weight-based dosing. Following results of the drug’s plasma level determined by enzyme-linked immunosorbent assay (ELISA), the maintenance dose should be individualized no later than eight weeks after initiation of treatment. Approval was based on a multicenter, open-label, Phase 3 trial (explorer7; n=133) that demonstrated a significant improvement in treated spontaneous and traumatic bleeding episodes with concizumab prophylaxis (n=33) compared to no prophylaxis (n=19) (estimated mean annualized bleeding rate [ABR] ratio, 0.14; 95% confidence interval, 0.07 to 0.29); this corresponded with an 86% reduction in the ABR for the concizumab group compared to the no prophylaxis group. Another TFPI antagonist, marstacimab-hncq (Hympavzi) received FDA approval in October 2024; however, it is indicated for routine prophylaxis in hemophilia A or B patients without factor VIII or factor IX inhibitors, respectively. In the hemophilia A space, Alhemo is expected to compete with emicizumab-kxwh (Hemlibra) which is also given SC and is indicated similarly for routine prophylaxis in all patients (newborn and older) with hemophilia A with or without factor VIII inhibitors. Anti-inhibitor coagulant complex (Feiba) is also indicated for routine prophylaxis in hemophilia A and B patients with inhibitors but is administered IV. Alhemo provides a SC prophylactic therapy for patients with hemophilia B with factor IV inhibitors who previously only had IV prophylactic options. The agent received Breakthrough Therapy and Orphan Drug designations and underwent Priority Review. Product availability is expected in mid-February 2025 with pricing to follow.  

Dec. 20, 2024 – vanzacaftor, tezacaftor and deutivacaftor (Alyftrek) 

The FDA has granted approval to Vertex’s cystic fibrosis (CF) triple therapy, Alyftrek. The agent is indicated for the treatment of CF in patients ≥ 6 years of age who have at least one F508del mutation or another responsive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Alyftrek is a triple combination CFTR modulator that combines deutivacaftor, a CFTR potentiator, tezacaftor and vanzacaftor. It is supplied in fixed-dose combination tablets containing vanzacaftor 4 mg, tezacaftor 20 mg and deutivacaftor 50 mg or vanzacaftor 10 mg, tezacaftor 50 mg and deutivacaftor 125 mg. If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one indicated mutation. The recommended dosage is given with fat-containing food orally once daily and is dependent on patient age and body weight. Approval was based on two randomized, double-blind, active-controlled trials (SKYLINE trials; n=971) comparing the agent with the combination therapy elexacaftor, tezacaftor and ivacaftor + ivacaftor (Trikafta). In both trials, Alyftrek demonstrated non-inferiority to Trikafta for the primary efficacy endpoint assessing the mean absolute change in percent predicted forced expiratory volume in one second (ppFEV₁) from baseline through week 24 (least-squares mean difference of 0.2% for both studies; p<0.0001). Alyftrek is the first, once-daily CFTR modulator and is expected to compete with other similarly indicated agents such as tezacaftor/ivacaftor + ivacaftor (Symdeko) or Trikafta (indicated for ≥ 6 years of age and ≥ 2 years of age, respectively). The agent was reviewed under Priority Review and received Orphan Drug designation. Alyftrek carries a boxed warning for drug-induced liver injury and liver failure. Product is available with an AWP of $34,085.06 per box containing a 28-day supply. 

Jan. 17, 2025 – datopotamab deruxtecan-dlnk (Datroway) 

Daiichi Sankyo’s Datroway has received FDA approval for the treatment of adults with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (immunohistochemistry [IHC] 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease. This Trop-2-directed antibody and topoisomerase inhibitor conjugate is supplied as 100 mg of lyophilized powder in a single-dose vial. It is administered as a weight-based dose given via an IV infusion by an HCP once every three weeks until disease progression or unacceptable toxicity. Administration requires a setting where cardiopulmonary resuscitation (CPR) equipment/medications are available. Ophthalmic examinations should be conducted at the start of therapy, annually, at the conclusion of treatment and as clinically warranted due to the risk of ocular adverse reactions. Monitoring with each infusion and premedications (eye drops, mouthwash, antihistamine, antipyretic, antiemetics) should be given as described in product labeling. Approval was based on a Phase 3, open-label, randomized trial (TROPION-Breast01; n=732) which showed that after a median follow-up of 10.8 months, datopotamab deruxtecan (Dato-DXd) demonstrated a 37% reduction in the risk of progression or death compared with investigator's choice of chemotherapy (ICC) (HR, 0.63; p<0.0001); this corresponded with a median PFS of 6.9 months with Dato-DXd versus 4.9 months with ICC. Sacituzumab govitecan-hziy (Trodelvy) is also a Trop-2-directed antibody and topoisomerase inhibitor conjugate. It is indicated for adults with unresectable locally advanced or metastatic HR-positive, HER2-negative breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. The FDA’s review of Datroway utilized Assessment Aid. The product is commercially available with an AWP of $5,869.28 per vial.