FDA Approvals Roundup: Pylarify, Lybalvi, Lumakras
New approvalsPylarify cleared for PSMA-targeted PET imaging in prostate cancer
Progenics’ Pylarify (piflufolastat F 18 injection) has been approved for use in positron emission tomography (PET) imaging of prostate-specific membrane antigen‒positive lesions in men with prostate cancer with suspected metastasis or recurrence.
The approval of Pylarify, a radioactive diagnostic agent, was based on safety and efficacy findings from the OSPREY and CONDOR trials. In the OSPREY trial, a cohort of 268 patients, who were candidates for surgical removal of the prostate gland and pelvic lymph nodes and considered at higher risk for metastasis, underwent PET/CT scans with Pylarify. Of the patients who underwent surgery, those with positive readings in the pelvic lymph nodes on Pylarify PET had a clinically important rate of metastatic cancer confirmed by surgical pathology. Findings from the CONDOR trial, with 208 patients, demonstrated that Pylarify PET can detect sites of disease in patients with biochemical evidence of recurrent prostate cancer, which could provide important information on the approach to therapy.
Pylarify received priority review designation for this approval.
Lybalvi gets the go-ahead for treating schizophrenia and bipolar I disorder
Alkermes’ Lybalvi (olanzapine and samidorphan) has been approved for use in adults with schizophrenia or bipolar I disorder as a maintenance monotherapy or for the acute treatment of manic or mixed episodes. It can be used as monotherapy or as an adjunct to lithium or valproate.
Lybalvi is a once-daily oral combination of olanzapine, an atypical antipsychotic agent, and the opioid antagonist samidorphan, a new chemical entity.
Approval of Lybalvi was based on findings from the ENLIGHTEN clinical trials. Findings from ENLIGHTEN-1, a 4-week, randomized, double-blind, placebo- and active-controlled efficacy study in patients with schizophrenia, showed a statistically significant improvement in symptom severity in patients treated with the combination study drug compared with both placebo and olanzapine alone. Findings from the Phase 3, randomized, 24-week ENLIGHTEN-2 study, also in patients with schizophrenia, showed those receiving Lybalvi gained statistically significantly less weight compared with patients receiving olanzapine alone.
Lybalvi was approved under the 505(b)(2) regulatory pathway, based on data from 27 clinical studies, including 18 studies evaluating Lybalvi and 9 studies evaluating samidorphan alone, and the FDA's findings of safety and effectiveness of olanzapine in the treatment of bipolar I disorder and schizophrenia.
Lumakras nabs accelerated approval for KRAS G12C‒mutated NSCLC
Amgen’s Lumakras (sotorasib) has been granted accelerated approval for treating previously treated adults who have KRAS G12C‒mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as detected by FDA-approved companion diagnostics, Qiagen therascreen KRAS RGQ PCR kit (tissue) and the Guardant360 CDx (plasma).
The approval of Lumakras was based on findings from the multicenter, single-arm, open-label CodeBreaK 100 trial in 124 patients in the indicated population, whose disease had progressed. They received the study drug daily until disease progression or unacceptable toxicity. The objective response rate (ORR), according to RECIST 1.1, was 36% (95% confidence interval (CI), 28% to 45%) with a median duration of response (DoR) of 10 months (range, 1.3+, 11.1).
The accelerated approval for this indication was based on ORR and DoR findings. Continued approval for this indication may depend on verification and description of clinical benefit in a confirmatory trial or trials. In particular, the approved oral dose of 960 mg was based on available supporting clinical data and pharmacokinetic and pharmacodynamic modeling. As part of the evaluation for the accelerated approval, the sponsor is required to conduct a postmarketing trial on the clinical impact of a lower dose.
This review was conducted under Project Orbis, with the FDA collaborating with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada, and the UK Medicines and Healthcare products Regulatory Agency. It used the real-time oncology review pilot program, the assessment aid, and the product quality assessment aid.
The application was granted priority review and fast-track, breakthrough therapy, and orphan drug designations.
Truseltiq okayed for metastatic cholangiocarcinoma
QED Therapeutics’ Truseltiq (infigratinib) has been approved for use in adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement.
The agency also approved FoundationOne CDx (Foundation Medicine) as a companion diagnostic device for treatment with Truseltiq .
Approval of Truseltiq was based on efficacy findings from a multicenter, open-label, single-arm trial in 108 patients in the indicated population who received Truseltiq until disease progression or unacceptable toxicity. In the trial, ORR was 23% (95% CI, 16% to 32%), with 1 complete response and 24 partial responses. MedianDoR was 5 months (95% CI: 3.7, 9.3). Eight of the 23 responders maintained the response for 6 months or more.
This indication is approved under accelerated approval based on the ORR and DoR findings. Its continued approval could depend on verification and description of clinical benefit in a confirmatory trial or trials.
The review was conducted under Project Orbis, for which FDA collaborated with the Australian Therapeutic Goods Administration and Health Canada. It used the real-time oncology review pilot program, assessment aid, and product quality assessment aid.
The application was granted priority review and fast-track and orphan drug designations.
Camcevi approved as depot formulation for treating advanced prostate cancer
Foresee’s Camcevi 42 mg (leuprolide mesylate) has been approved as a treatment for patients with advanced prostate cancer. The therapy is available as a ready-to-use, 6-month, subcutaneous depot formulation.
Approval of Camcevi, a gonadotropin-releasing hormone agonist, was based on efficacy and safety findings in a Phase 3, open-label, single-arm trial of 137 patients from the indicated population who received the study drug injection every 6 months. The primary efficacy end point was the percentage of patients with suppression of serum testosterone by day 28 of treatment and from day 28 to day 336 in the intent-to-treat population. The primary efficacy endpoint was successfully achieved in 97% of patients, with mean testosterone concentration suppressed below castrate levels on day 28.
New indications
Kedrab use as postexposure rabies treatment expanded to include children
Kedrion and Kamada’s Kedrab (human rabies immune globulin [HRIG]) has received a label update for children to receive passive, transient postexposure prophylaxis (PEP) of rabies infection following contact with a rabid, or possibly rabid, animal.
The new updates are based on data from the Kedrab US postmarketing Pediatric Study. Additional evidence to support the use of Kedrab in children came from real-world evidence. Kamada has been selling the HRIG product since 2003 in numerous territories outside of the US under the brand name Kamrab.
Under a clinical development and marketing agreement between the two companies, the Israeli-based Kamada holds the license for Kedrab, and Kedrion has exclusive rights to commercialize the product in the US.
Kedrab was approved originally approved in the US in 2017.
Nurtec ODT handed new indication for migraine prevention
Biohaven’s Nurtec ODT (rimegepant) has received a new indication for the preventive treatment of migraine in adults with episodic migraine. Its use was also expanded for treating both acute and preventive therapy in the same patient.
The FDA approval of Nurtec ODT is based on a double-blind, randomized, placebo-controlled Phase 3 trial with an open label extension. Primary study endpoint results demonstrated that Nurtec ODT was superior to placebo, decreasing monthly migraine days by 4.3 days/month after 3 months of treatment. The preventive effects of Nurtec ODT were seen as early as the first week of therapy. Further, a key secondary endpoint result showed that about half the patients receiving Nurtec ODT had a 50% or greater reduction in the number of moderate-to-severe migraine days a month.
Nurtec ODT was previously approved for acute treatment in all eligible adult patients with migraine.
Cosentyx use extended to pediatric patients with plaque psoriasis
Novartis’s Cosentyx (secukinumab) has received expanded approval for treating moderate to severe plaque psoriasis in children aged 6 years or older who are candidates for systemic therapy or phototherapy.
The therapy can be administered by an adult caregiver outside of a healthcare provider's office from a single-dose prefilled syringe or Cosentyx’s Sensoready pen. The caregiver must have received proper training in injection technique.
Approval of Cosentyx was based on two Phase 3 studies in children aged 6 to younger than 18 years from the indicated population, both of which showed reduced psoriasis severity over the course of the studies.
Cosentyx was originally approved in 2015 to treat adults with severe plaque psoriasis. It is also approved for use in adults with active psoriatic arthritis, active ankylosing spondylitis, or active non–radiographic axial spondyloarthritis.