FDA Roundup: Blenrep, Olinvyk, Lampit
A weekly update on new drug approvals and indications from the US Food and Drug Administration (FDA).New approvals
Blenrep okayed for multiple myeloma in heavily pretreated adults
GlaxoSmithKline’s Blenrep (belantamab mafodotin-blmf injection) has received accelerated approval for relapsed or refractory multiple myeloma in adults with previous failed treatments, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody.
Blenrep is the first anti-BCMA (B-cell maturation antigen) therapy to receive approval anywhere in the world. Accelerated approval was based on response rate. The drug’s continued approval for this indication may depend on clinical benefit findings in confirmatory trials.
The drug’s efficacy, based on overall response rate (ORR) and response duration, was evaluated in the open-label, multicenter DREAMM-2 trial. Patients received either the recommended dose of 2.5 mg/kg of the study drug, or 3.4 mg/kg, every 3 weeks until disease progression or extreme toxicity. Patients receiving the 2.5 mg/kg dose showed an ORR of 31%, with 73% of responders in the group having response durations of 6 months or longer.
Blenrep comes with a boxed warning for risk of ocular toxicity so it will be available only under a risk evaluation and mitigation strategy safety program. The review process and timeline were aided by use of the real-time oncology review, which facilitates pre-application data submission, and the assessment aid. Blenrep carried orphan drug and breakthrough therapy designations and received priority review for this indication.
Olinvyk approved for pain management in controlled settings
Trevena’s Olinvyk (oliceridine injection) has been approved for short-term IV use for managing moderate to severe pain in adults in hospital or controlled clinical settings. The rapid-acting opioid agonist comes with a recommended daily dose limit of 27 mg.
“[Olinvyk] is indicated only for use in a controlled clinical setting, meaning under medical supervision and not for use in a take-home prescription,” said Douglas Throckmorton, MD, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research.
Olinvyk’s efficacy was demonstrated in the randomized, controlled, open-label APOLLO studies of 790 patients who had undergone bunion or abdominal surgery. Patients who received Olinvyk reported diminished pain compared with those who received placebo. Its safety was evaluated in an open-label study with 768 patients who received at least one dose of Olinvyk after surgical procedure. Its safety profile matched that of other opioids.
Olinvyk carries a boxed warning about addiction, abuse and misuse, depression, and other risks.
Trevena originally submitted a new drug application in 2017, for which it received a breakthrough designation. In October 2018, FDA’s Anesthetic and Analgesic Drug Products Advisory Committee voted 8-7 against the drug’s approval. The company resubmitted a new drug application in February this year. It noted in its resubmission that Olinvyk is a “new chemical entity with a novel mechanism of action,” capable of targeting newly discovered pathways.
Lampit greenlighted for treating Chagas disease in children
Bayer’s Lampit (nifurtimox tablet) has received accelerated approval for treating Chagas disease in pediatric patients younger than 18 years, including newborns weighing at least 2.5 kg.
Chagas is an infectious tropical disease caused by the Trypanosoma cruzi parasite, transmitted to humans mainly in the feces of infected insects, but also mother to child during pregnancy and birth, and through blood transfusion or organ transplant.
Lampit’s approval was based on efficacy, safety, and pharmacokinetic findings from the phase 3, prospective, randomized, double-blind CHICO study in 330 children with Chagas disease at sites in Argentina, Bolivia, and Colombia. The children were randomly assigned to receive a 60- or 30-day (n = 219 or n = 111) treatment regimen and followed up a year after treatment cessation. Serological response – measured by lysate and recombinant ELISA results – showed superiority in the 60-day arm over the 30-day arm.
Children will be followed for another 3 years to confirm the study drug’s efficacy and safety. Because the drug received accelerated approval, its continued approval for this indication will depend on demonstration of clinical benefit in confirmatory studies.
Lampit is currently registered in Argentina, Chile, El Salvador, Guatemala, Honduras, and Uruguay for the treating acute and chronic Chagas disease in adults and children. It was first introduced by Bayer in the 1970s and is on the World Health Organization List of Essential Medicines.
Evrysdi approved as first oral treatment for spinal muscular atrophy
Genentech’s Evrysdi (risdiplam) has been approved as the first oral therapy for spinal muscular atrophy (SMA) in patients aged 2 months or older.
SMA is a rare, sometimes fatal, hereditary disease that affects muscle strength and movement of loss of motor neurons that control movement. Evrysdi is the first oral therapy approved for SMA, and the second approval for the disease to date, after the 2016 approval of Biogen’s Spinraza (nusinersen injection).
The approval was based on findings in 2 studies evaluating Evrysdi’s efficacy in patients with infantile-onset and later-onset SMA. In the open-label study of 21 patients with infantile-onset SMA, efficacy was established if a child could sit without support for at least 5 seconds and survive without ventilation. After 12 months of treatment, 41% of children could sit independently for the stipulated period. After 23 months or more, 81% of patients were not using permanent ventilation. Both those findings were improvements over disease progression in untreated children.
In the randomized, placebo-controlled, later-onset study, investigators monitored the 1-year change from baseline in a motor-function test in 180 patients with disease onset between 2-25 years. Patients in the study drug group showed an average increase of 1.36 in their score after 1 year, compared with a 0.19 decrease in the scores of patients receiving placebo.
The application was granted a fast track and orphan drug designations and received priority review as well as a rare pediatric disease priority review voucher.
Viltepso approved as targeted Duchenne muscular dystrophy treatment
NS Pharma’s injectable Viltepso (viltolarsen) has received accelerated approval to treat Duchenne muscular dystrophy (DMD) in a subset of patients with a confirmed mutation of the rare and progressive neuromuscular disorder.
Exons that code for the protein dystrophin, which helps keep muscles intact, are defective in DMD. Skipping exon 53 during protein encoding increases dystrophin production for the 8% of DMD patients whose gene mutations are amenable to exon 53 skipping.
Viltepso’s ability to boost dystrophin production was seen in one of two studies of a total of 32 men with confirmed DMD. The study of 16 patients saw dystrophin levels increase from 0.6% of normal to 5.9% of normal by study week 25 in the 8 patients who received Viltepso. This increase, concluded FDA, was reasonably likely to have clinical benefit for individuals with DMD.
FDA noted in the approval that clinical benefit has not been established, but that the risk-benefit calculation for a treatment for DMD and the lack of available therapies warranted approval. Viltepso’s benefit must now be confirmed in a clinical trial that targets time-to-standing as a clinically meaningful endpoint.
Viltepso, a phosphorodiamidate-linked morpholino oligomer, was also granted priority review designation.
New indication
Dovato nabs expanded indication for previously treated HIV-1 in adults
ViiV Healthcare’s Dovato (dolutegravir-lamivudine tablet) has received an expanded indication as a complete regimen for HIV-1 infection in previously treated adults.
The two-drug combination therapy was originally approved in 2019 for use in patients with no antiretroviral treatment history or known resistance to dolutegravir or lamivudine. The expanded indication is for replacing an antiretroviral (ARV) regimen in virologically suppressed adults on an ARV regimen and who have no history of treatment failure or known resistance to Dovato’s two component drugs.
Approval for the expanded indication was based on findings from the phase 3 TANGO study, showing that adults with HIV-1 who had maintained virologic suppression on an alafenamide fumarate‒containing regimen of at least three drugs, were able to maintain similar rates of virologic suppression after switching to Dovato. Safety results for patients who switched to Dovato were consistent with the product labeling for the component drugs.