Drug Approvals Monthly Update: April 2024

April 25, 2024

This monthly update of United States (U.S.) Food and Drug Administration (FDA) approvals provides a review of newly approved specialty drugs, new indications and recent first-time generic launches.

Specialty

New drugs

3/18/2024 Lenmeldy™ (atidarsagene autotemcel)

Lenmeldy is an autologous hematopoietic stem cell-based gene therapy by Orchard Therapeutics, which was FDA approved for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ), or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD), collectively known as early-onset MLD. It is the only treatment approved for patients with early-onset MLD. Lenmeldy was granted Orphan Drug, Rare Pediatric Disease and Regenerative Medicines Advanced Therapy designations as well as a Priority Review. It is approved as a single-dose cell suspension for intravenous (IV) infusion as a one-time dose. Patients are required to undergo hematopoietic stem cell mobilization (HSC) followed by apheresis to obtain CD34+ cells for manufacturing. Myeloablative conditioning is required before the infusion of Lenmeldy. In clinical trials, Lenmeldy significantly extended overall survival and preserved motor function and cognitive skills in most late infantile MLD patients compared to untreated patients who showed severe cognitive and motor impairments. Motor function and cognitive skills were also preserved in some early juvenile MLD patients. Orchard is in the process of qualifying five specialized treatment centers to administer the therapy. A wholesale acquisition cost (WAC) of $4.25 million for the one-time treatment has been set by Orchard.

3/19/2024 Tryvio™ (aprocitentan)

The FDA approved Tryvio, a dual endothelin (ET) receptor antagonist, for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adults who are not adequately controlled on other drugs. It is the first antihypertensive agent to target the ET pathway. Tryvio is approved as an oral tablet that is dosed once daily. In the phase 3, PRECISIONS trial, Tryvio doses of 12.5 mg and 25 mg led to a significant reduction in office systolic blood pressure (SBP) at week 4 (placebo-adjusted least square [LS] mean change, -3.8 mm Hg and -3.7 mm Hg, respectively; p<0.005 for both).¹ A reduction in office diastolic blood pressure (DBP) was also seen with each dose (placebo-adjusted LS mean change, -3.9 mm Hg and -4.5 mm Hg, respectively). Tryvio carries a Boxed warning for embryo-fetal toxicity and is only available through a restricted Risk Evaluation and Mitigation Strategy (REMS) program. Idorsia plans to launch Tryvio in 2H 2024. Pricing will follow.

3/21/2024 Duvyzat™ (givinostat)

The FDA approved Duvyzat, a histone deacetylase (HDAC) inhibitor, for the treatment of Duchenne muscular dystrophy (DMD) in patients ≥ 6 years of age. Duvyzat was granted Fast Track, Orphan Drug, and Rare Pediatric Disease designations as well as a Priority Review. It will be available as an oral suspension for twice daily dosing. Approval was based on the double-blind, phase 3 EPIDYS trial in ambulant boys. The study demonstrated after 18 months of treatment, Duvyzat, as add-on to background standard steroid therapy, led to a statistically significant less decline in the time it took to climb 4 stairs (difference versus placebo, 1.78 seconds; p=0.037).²  Secondary endpoints also showed less worsening in other physical function scores. Duvyzat is the first nonsteroidal drug approved to treat patients with all genetic variants of DMD. Italfarmaco is launching a subsidiary, ITF Therapeutics, to bring Duvyzat to patients in the U.S. Pricing to follow.

3/22/2024 Opsynvi® (macitentan/tadalafil)

The FDA approved Opsynvi under their 505(b)(2) pathway. It is a combination of macitentan, an endothelin receptor antagonist (ERA), and tadalafil, a phosphodiesterase 5 (PDE5) inhibitor, indicated for chronic treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adult patients of WHO functional class (FC) II-III. Opsynvi is designated as an Orphan Drug. The separate components of Opsynvi are available as Opsumit® (macitentan) and Adcirca® (tadalafil). Like Opsumit, Opsynvi carries a Boxed warning for embryo-fetal toxicity and requires female patients to enroll in the REMS program. Actelion launched Opsynvi in April 2024, with an annual WAC of $153,700 which is less than taking the 2 products separately.

3/26/2024 Winrevair™ (sotatercept-csrk)

Merck received FDA approval for their activin signaling inhibitor, Winrevair, for the treatment of adults with PAH (WHO Group I) to increase exercise capacity, improve WHO FC and reduce the risk of clinical worsening events. This agent treats the cause of PAH by improving the balance between pro- and anti-proliferative signaling to regulating vascular cell proliferation. It received Breakthrough Therapy and Orphan Drug designations and a Priority Review from the FDA. A weight-based dose is administered subcutaneously (SC) once every three weeks, which may be administered by the patient or caregiver with proper training. The approval of Winrevair was based on the placebo-controlled, phase 3 STELLAR trial that reported, at week 24, an increase in 6-minute walking distance (primary endpoint) by 41 meters when Winrevair was added to background therapy.³ There were also significant improvements in secondary endpoints including risk of death and clinical worsening of PAH. Winrevair was launched in April 2024. The estimated annual WAC ranges from $240,000 to $480,000, depending on patient weight.

3/27/2024 Vafseo® (vadadustat)

Vafseo, by Akebia, was FDA approved for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for ≥ 3 months. It’s not indicated for use: (1) as a substitute for transfusion in patients requiring immediate correction of anemia, and (2) in patients with anemia due to CKD who are not on dialysis. In addition, it has not been shown to improve quality of life, fatigue, or patient well-being. Vafseo is the second oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor approved by the FDA, following the approval of Jesduvroq® (daprodustat; approved in patients (≥ 4 months of age) in 2023. Vafseo is approved as oral tablets with a once-daily dosage that is adjusted to a target Hb level of 10 to 11 g/dL. In the open-label INNO2VATE-1 and INNO2VATE-2 trials, Vafseo was non-inferior to darbepoetin alfa based on the primary endpoint of mean change in Hb levels from baseline to weeks 24 to 36.4 Like erythropoiesis-stimulating agents (ESAs) and Jesduvroq, Vafseo carries a Boxed warning for increased risk of death, myocardial infarction (MI), stroke, venous thromboembolic event, and vascular access thrombosis. The launch of Vafseo is expected in the 2H 2024, with pricing to follow.

3/29/2024 Voydeya™ (danicopan)

Alexion received FDA approval for Voydeya, a first-in-class, oral complement factor D inhibitor. It’s indicated as add-on therapy to ravulizumab or eculizumab for the treatment of extravascular hemolysis (EVH) in adults with paroxysmal nocturnal hemoglobinuria (PNH). The agent received Breakthrough Therapy and Orphan Drug designations from the FDA. It will be available as tablets and dosed orally three times a day, with dosage adjusted based on clinical response. FDA approval was based on data from the double-blind, phase 3 ALPHA trial, in which Voydeya or placebo were added to background therapy. The study reported that Voydeya led to a significant mean increase in Hb from baseline to week 12 (primary endpoint) (difference versus placebo, 2.4 g/dL; p=0.0007).5 In addition, significantly more patients on Voydeya achieved ≥ 2 g/dL increase in Hb without the need for transfusion (difference versus placebo, 46.9%; p<0.0001) and avoided transfusion (difference versus placebo, 41.7%; p=0.0004) through week 12. Voydeya carries a Boxed warning regarding serious infections caused by encapsulated bacteria and is only available through a REMS program. Alexion has launched Voydeya in the U.S.

New biosimilars

4/16/2024 Selarsdi™ (ustekinumab-aekn)

Alvotech and Teva announced the FDA approved Selarsdi as a biosimilar to Janssen’s Stelara®, a human interleukin-12 and -23 antagonist. Selarsdi is indicated for the treatment of moderate to severe plaque psoriasis and for active psoriatic arthritis in adults and pediatric patients ≥ 6 years of age. Unlike its reference product, Selarsdi it does not carry indications for Crohn’s disease and ulcerative colitis. Selarsdi is the second ustekinumab biosimilar approved in the U.S.; however, is not interchangeable for Stelara like Wezlana™ (ustekinumab-auub) by Amgen. Selarsdi is estimated to launch on or after February 21, 2025, with pricing to follow.

New indications

3/18/2024 Spevigo® (spesolimab-sbzo)

Boehringer Ingelheim received an expanded indication for Spevigo, an interleukin-36 receptor antagonist, for the treatment of generalized pustular psoriasis (GPP) in adults and pediatric patients ≥ 12 years of age weighing ≥ 40 kg; previously, it was only indicated for treatment of GPP flares in adults. It also received approval of a 150 mg/mL single-dose prefilled syringe for subcutaneous (SC) administration of every four-week maintenance doses; doses to treat a GPP flare are administered intravenously (IV). The Effisayil 2 study demonstrated an 84% reduction in GPP flares after 48 weeks with Spevigo compared to placebo.6

3/22/2024 Ixinity® (coagulation factor IX, recombinant)

The FDA expanded the indication for Medexus’ Ixinity for on-demand, prophylactic, and perioperative treatment of pediatric patients < 12 years of age with hemophilia B; it is now approved for use in all ages. The dosage in this age group differed from older populations, as children < 12 years of age showed higher factor IX body weight-adjusted clearance, shorter half-life, and lower recovery compared to adolescents and adults.7

3/22/2024 Ultomiris® (ravulizumab-cwvz)

The FDA approved a new indication for Alexion’s complement inhibitor, Ultomiris, for the treatment of adults with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin 4 (AQP4) antibody positive. For NMOSD, Ultomiris is administered IV using a weight-based dose with an initial loading dose, followed by maintenance dosing every 8 weeks. In the phase 3, open-label CHAMPION-NMOSD trial, patients who received Ultomiris did not experience NMOSD relapse during a median treatment duration of 73 weeks (hazard ratio [HR], 98.6%; p<0.0001); the placebo group of the eculizumab PREVENT trial was used as an external comparator.8

3/22/2024 Elahere® (mirvetuximab soravtansine-gynx)

The FDA granted a full approval to Immunogen’s folate receptor alpha (FRα)-directed antibody and microtubule inhibitor conjugate, Elahere, for the treatment of adults with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Previously, Elahere was given an Accelerated Approval for this indication. The MIRASOL trial confirmed a significant improvement in endpoints with Elahere compared to chemotherapy, including in median overall survival (OS) (16.5 versus 12.7 months, respectively; p=0.0045), median progression-free survival (PFS) (5.6 versus 4 months, respectively; p<0.0001), and objective response rate (ORR) (42% versus 16%, respectively; p<0.0001).9

4/04/2024 Abecma® (idecabtagene vicleucel)

Bristol-Myer Squibb’s B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR T) therapy, Abecma, received an expanded indication for the treatment of adults with relapsing or refractory (R/R) multiple myeloma (MM) with at least two prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. This expanded approval allows for earlier treatment with Abecma than previously indicated. Benefit in patients who had relapsed after two to four prior lines of therapy was demonstrated in the KarMMa-3 trial. The progression-free survival (PFS) was increased by about 51% with Abecma compared to standard therapy.10

4/05/2024 Carvykti® (ciltacabtagene autotemcel)

Carvykti gained a new indication for the treatment of adults with R/R MM who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. This new indication makes Carvykti the only BCMA-directed therapy to treat MM after first relapse. In the CARTITUDE-4 trial, the CAR T therapy reduced the risk of disease progression or death by 59% compared to standard therapy (pomalidomide and dexamethasone plus bortezomib or daratumumab) when treating earlier relapses.¹¹

4/05/2024 Fasenra® (benralizumab)

Fasenra’s indication as add-on maintenance treatment of patients with severe asthma and with an eosinophilic phenotype has been expanded to include pediatric patients 6 to 11 years of age; previously, it was only approved for those 12 years and older. The dosage in this new age group is weight-based and should be administered by a caregiver or health care professional. Safety and efficacy of the interleukin-5 receptor alpha-directed cytolytic monoclonal antibody in patients 6 to 11 years old was demonstrated in adequate and well-controlled trials in adults and adolescents and pharmacokinetic, pharmacodynamic, and safety data in pediatric patients aged 6 to 11 years.¹²

4/05/2024 Enhertu® (fam-trastuzumab deruxtecan-nxki)

The FDA awarded an Accelerated Approval for Enhertu, a HER2-directed antibody and topoisomerase inhibitor conjugate, for the treatment of adults with unresectable or metastatic HER2-positive (IHC3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options. Continued approval for this indication may depend on results from a confirmatory trial verifying clinical benefit. Across three clinical trials, treatment with Enhertu led to an objective response rate (ORR) and median duration of response (DOR) (respectively) of 51.4% and 19.4 months in patients with solid tumors (DESTINY-PanTumor02), 52.9% and 3.9 months in patients with non-small cell lung cancer (DESTINY-Lung01), and 46.9% and 5.5 months in patients with colorectal cancer (DESTINY-CRC02); patients in these trials met criteria of the approved indication.¹³ Enhertu was granted a Priority Review and a Breakthrough Therapy designation for this indication.

Traditional

New drugs

3/29/2024 Risvan® (risperidone extended-release injection)

Reviewed under the 505(b)(2) pathway, the FDA approved Risvan for the treatment of schizophrenia in adults. The agent provides immediate and sustained plasma drug levels and does not require loading doses or supplementation with oral risperidone. After establishing tolerability with oral risperidone, Risvan is administered intramuscularly (IM) once monthly into the gluteal or deltoid muscle by health care professional. Notably, patients who are on stable oral risperidone daily doses < 3 mg or > 4 mg may not be candidates for this product. Risvan approval is based on the PRISMA-3 study, which reported positive efficacy and safety results in patients with schizophrenia, with adjusted difference of approximately 13 points on the Positive and Negative Syndrome Scale (PANSS) total score with Risvan compared to placebo.14 Laboratorios Farmacéuticos ROVI has not announced the launch timeframe or pricing information for Risvan.

4/3/2024 Zevtera® (ceftobiprole medocaril)

Zevtera, an advanced generation cephalosporin antibiotic by Basilea, has been FDA approved for the treatment of: (1) adults with Staphylococcus aureus bacteremia (SAB), including those with right-sided infective endocarditis; (2) adults with acute bacterial skin and skin structure infections (ABSSSI); and (3) adult and pediatric patients ≥ 3 months of age with community-acquired bacterial pneumonia (CABP). Zevtera was granted a Priority Review and Fast Track and Qualified Infectious Disease Product designations for the three indications. It is administered IV over 2 hours. Dosing frequency (every 6 or 8 hours) and duration (range, 5 to 42 days) depends on the condition being treated. In clinical trials, Zevtera was noninferior to daptomycin for the treatment of SAB, noninferior to vancomycin plus aztreonam for the treatment of ABSSSI, and noninferior to ceftriaxone, with or without linezolid, for the treatment of CABP.15,16,17 Launch of Zevtera will be determined after Basilia has entered a commercialization partnership. Pricing to follow.

New indications

3/15/2024 Edurant® and Edurant® PED (rilpivirine)

The FDA expanded the indication for Janssen’s human immunodeficiency virus type 1 (HIV-1) specific non-nucleoside reverse transcriptase inhibitor (NNRTI), Edurant, for the treatment of HIV-1 in combination with other antiretroviral therapies (ARVs) in treatment-naïve children (with HIV-1 RNA <100,000 copies/mL) ≥ 2 years of age and weighing ≥ 14 kg and < 25 kg. Previously, it was only approved for use in treatment-naïve patients ≥ 12 years of age weighting ≥ 35 kg. To accommodate use in this younger population, the FDA also approved Edurant PED, a 2.5 mg tablet for oral suspension. Notably, Edurant PED tablets should not be substituted with Edurant tablets on a mg-per-mg basis due to pharmacokinetic differences. FDA approval for use in children was supported by results from the PAINT and PICTURE trials that demonstrated safety and efficacy of rilpivirine in combination with other ARVs in this population.18 Launch timeframe and pricing of Edurant PED have not been announced.

3/22/2024 Nexletol® (bempedoic acid) and Nexlizet® (bempedoic acid/ezetimibe)  

The FDA approved a new indication for Nexletol and Nexlizet to reduce the risk of MI and coronary revascularization in adults who are unable to take recommended statin therapy (including those not taking a statin) with: (1) established cardiovascular disease (CVD), or (2) a high risk for a CVD event but without established CVD. The dosages for this new indication for both agents are consistent with their indication for cholesterol-reduction. Approval for the new indication is supported by data from the CLEAR Outcomes trial that reported a 13% reduction in composite primary endpoint of major adverse cardiovascular event (MACE)-4, which includes CV death, nonfatal MI, nonfatal stroke and coronary revascularization.19 In addition, the FDA expanded the cholesterol lowering indication in both primary and secondary prevention patients.

3/27/2024 Vemlidy® (tenofovir alafenamide)

Gilead received an expanded indication for the nucleoside analog reverse transcriptase inhibitor, Vemlidy, for treatment of chronic hepatitis B virus (HBV) infection to include pediatric patients ages 6 years to < 12 years of age and weighing ≥ 25 kg with compensated liver disease; previously, it was only approved for use in those ≥ 12 years of age. The dosage in the new age group is consistent with adolescents and adults. No clinically meaningful differences in pharmacokinetics or safety were seen between adults and younger populations.20

4/02/2024 Fanapt® (iloperidone)

The FDA approved a new indication for the atypical antipsychotic, Fanapt, for acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. In a phase 3, double-blind trial (NCT04819776), Fanapt demonstrated significant improvement compared to placebo at week 4 for the primary endpoint of change from baseline in the Young Mania Rating Scale (YMRS) total score (difference, −4; p=0.000008).²¹ When initiating therapy with Fanapt, the dose is gradually increased to a target of 12 mg twice daily by day 5 of treatment.

4/05/2024 Dovato® (dolutegravir/lamivudine)

The FDA expanded use of Dovato as a complete regimen to treat HIV-1 infection to include adolescents ≥ 12 years of age and weighing ≥ 25 kg. Dovato can be used in patients with no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA < 50 copies/mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of Dovato. It was previously only approved for use in adults. Dovato, by Viiv Healthcare, is the first oral, two-drug combination, single-tablet regimen to be available for adolescents living with HIV. The once daily dosage is the same for adolescents and adult patients.

First generic drug launches

Oracea (doxycycline) 40 mg oral capsule: Lupin launched its generic version of Oracea capsules on April 9, 2024. Multiple other generic filers who reach settlement agreements with Galderma may have an opportunity to launch their generic versions. Oracea generated $123 million in annual U.S. sales in 2023.

References

1. PRECISION trial: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02034-7/abstract.

2. EPIDYS trial: https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(24)00036-X/fulltext.

3. Winrevair labeling: accessdata.fda.gov/drugsatfda_docs/label/2024/761363s000lbl.pdf.

4. INNO2VATE-1 and INNO2VATE-2 trials: https://www.nejm.org/doi/full/10.1056/NEJMoa2025956.

5. Voydeya labeling: https://alexion.com/Documents/voydeya_uspi#xd_co_f=ZmYwMThlZmEtNGVhZi00MTY1LTg2YTEtZjE2ZmNmOTc1OTQw~.

6. Spevigo labeling: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761244s003lbl.pdf.

7. Ixinity labeling: https://www.fda.gov/media/91715/download?attachment.

8. CHAMPION-NMOSD trial: https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26626.

9. FDA Press release. FDA approves mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer | FDA

10 Abecma labeling: https://www.fda.gov/media/147055/download?attachment.

11. Carvykti labeling: https://www.fda.gov/media/156560/download?attachment.

12. Fasenra labeling: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761070Orig1s020correctedlbl.pdf.

13. FDA Press release. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-her2.

14. Risvan labeling: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/214835s000lbl.pdf.

15. ERADICATE trial: https://www.nejm.org/doi/full/10.1056/NEJMoa2300220.

16. TARGET trial: https://academic.oup.com/cid/article/73/7/e1507/5902794?login=false.

17. NCT00326287 trial: https://www.sciencedirect.com/science/article/abs/pii/S0924857911004614.

18. Edurant and Edurant PED labeling: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/202022Orig1s020;%20s022lbl.pdf.

19. CLEAR Outcomes trial: https://www.nejm.org/doi/full/10.1056/NEJMoa2215024.

20. Vemlidy labeling: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/208464s016s017lbl.pdf.

21. NCT04819776: https://www.psychiatrist.com/jcp/efficacy-safety-iloperidone-in-bipolar-mania/.

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