Phase III and pivotal trial results — positive and negative, treated alike.
Merck and Moderna's personalized mRNA cancer vaccine, combined with Keytruda, met the primary endpoint of recurrence-free survival in a phase 3 trial in high-risk skin cancer, positioning the partners to potentially seek accelerated approval.
Why it matters: Positive phase 3 recurrence-free survival primary endpoint allows comparison with prior personalized vaccine trials.
Finerenone slowed kidney-function decline in adults without diabetes who had chronic kidney disease with albuminuria despite renin-angiotensin system inhibitors. In 1584 participants, the mean annual eGFR change from baseline to month 32 was -3.3 ml per minute per 1.73 m2 with finerenone versus -4.0 with placebo (difference, 0.7; P<0.001). The composite kidney or cardiovascular outcome was also less frequent (hazard ratio, 0.77; P=0.04), extending finerenone's benefit beyond the diabetic population.
Why it matters: It extends finerenone's kidney protection to CKD patients without diabetes, a population with no prior trial evidence.
In a phase 3 trial of relapsed or refractory multiple myeloma after at least one prior line of therapy, talquetamab plus daratumumab (Tal-D) or with pomalidomide (Tal-DP) beat daratumumab-pomalidomide-dexamethasone (DPd) on progression-free survival: 24-month estimates of 81.3% and 77.6% versus 51.2%, with hazard ratios of 0.28 and 0.33. Complete response or better reached 71.1% and 69.0% versus 34.5%, and MRD-negative complete response 52.3% and 46.3% versus 15.9%. The results position GPRC5D-directed bispecific therapy earlier in the treatment sequence.
Why it matters: Phase 3 data show talquetamab regimens outperforming standard daratumumab-based therapy in relapsed myeloma after just one prior line.
AstraZeneca has terminated the global late-stage eVOLVE-Lung02 trial of the PD-1/CTLA-4 bispecific antibody Volrustomig combined with chemotherapy. The study compared Volrustomig plus chemotherapy head-to-head with pembrolizumab plus chemotherapy as first-line treatment for metastatic non-small cell lung cancer with PD-L1 expression below fifty percent. AstraZeneca's other key bispecific is the PD-1/TIGIT antibody Rilvegostomig.
Why it matters: The head-to-head trial versus pembrolizumab plus chemotherapy provides a negative control for same-target bispecifics in first-line NSCLC.
EyePoint reported preliminary data from the pivotal Phase III LUGANO trial of DURAVYU 2.7 mg in wet AMD, and its shares fell 67% that day. LUGANO is the first of two pivotal Phase III trials in wet AMD; the other has not read out, and EyePoint has also started two Phase III trials in diabetic macular edema. Vorolanib was licensed to EyePoint by Betta Pharmaceuticals in February 2020 for development outside Greater China.
Why it matters: LUGANO was the first of two pivotal wet AMD Phase III trials, and its negative result adds uncertainty to the second wet AMD trial and two DME Phase III trials.
argenx reported that its Phase 2/3 ALKIVIA trial of subcutaneous Vyvgart Hytrulo (efgartigimod) in adult autoimmune myositis met its primary endpoint, and it plans to file a marketing application with the FDA on these data. The trial enrolled 264 patients; at week 52, the Vyvgart Hytrulo group showed a mean TIS improvement 15.4 points higher than placebo in the combined IMNM and DM population. The brief notes no targeted therapy is currently approved for this disease.
Why it matters: Topline data of 264 enrolled and TIS 15.4 points above placebo at week 52 let readers judge its potential in myositis, which lacks approved targeted drugs.
Ivonescimab plus paclitaxel or nab-paclitaxel as first-line therapy produced an objective response rate of 80.0% (95% CI 63.1-91.6) in 35 evaluable patients with locally advanced unresectable or metastatic triple-negative breast cancer, including 2 complete and 26 partial responses. In the 36-patient single-arm phase 2 trial, all patients had treatment-related adverse events, 58.3% were grade 3 or higher, and no treatment-related deaths occurred. The PD-1/VEGF bispecific plus chemotherapy pairing offers a first-line option for this population that merits further investigation.
Why it matters: It tests a PD-1/VEGF bispecific antibody as first-line therapy in triple-negative breast cancer, where systemic options are limited.
Amylyx Pharmaceuticals announced that its investigational drug avexitide met the primary endpoint in a Phase 3 trial for post-bariatric hypoglycemia (PBH). The drug group showed a 55% reduction in the rate of severe hypoglycemic events versus placebo, exceeding the prespecified statistical assumption of 35%. Co-CEO Justin Klee said that if approved, the drug could become the first treatment for PBH.
Why it matters: The article presents the prespecified 35% reduction assumption alongside the actual 55% reduction, so readers can gauge how far the effect exceeded the threshold.
Self-directed cognitive behavioral therapy for chronic pain (CBT-CP) with asynchronous personalized coach feedback outperformed clinician-delivered CBT-CP in 764 VHA patients with chronic musculoskeletal pain. Pain interference on the BPI-I at 4 months fell to 5.26 vs 6.23 (mean difference -0.98, P < .001), with superiority maintained at 6 and 12 months and higher session completion. Scalable self-directed CBT may be an effective alternative that increases uptake of this first-line treatment.
Why it matters: Self-directed therapy beat clinician-delivered CBT-CP in a large pragmatic trial, with effects sustained to 12 months.
EyePoint's investigational ophthalmic drug Duravyu failed to meet the primary endpoint in a Phase 3 trial for wet age-related macular degeneration (wet AMD): patients did not maintain vision with less frequent injections, underperforming standard treatment. The results imperil EyePoint's plan to seek regulatory approval for Duravyu; the company's stock plunged on the day, while shares of competitor Ocular Therapeutix rose.
Why it matters: Duravyu's Phase 3 miss rules out its lower-injection-frequency differentiation in wet AMD and reshapes the competitive field.
Amylyx Pharmaceuticals' GLP-1 receptor antagonist avexitide reduced severe hypoglycemic events by more than half in a phase 3 trial for a rare endocrine disease. The drug came from a $35 million acquisition, and the company is preparing to move forward with a marketing application.
Why it matters: The phase 3 trial halved severe hypoglycemic events, and the $35 million acquisition cost offers a benchmark for small companies cheaply inking late-stage assets and refiling for approval.
Ralinepag, an oral once-daily selective prostacyclin IP receptor agonist, halved the occurrence of a first clinical worsening event in pulmonary arterial hypertension compared with placebo in the phase 3 ADVANCE OUTCOMES trial. Of 687 patients, 64 (18%) of 350 on ralinepag had a first clinical worsening event versus 121 (36%) of 337 on placebo. Adverse events were the primary reason for treatment discontinuation in 65 (19%) of 350 on ralinepag and ten (3%) of 337 on placebo.
Why it matters: Phase 3 data show an oral prostacyclin receptor agonist halving clinical worsening events in PAH patients on contemporary background therapy.
EyePoint's Duravyu missed the best-corrected visual acuity primary endpoint in a phase 3 trial for wet AMD, and shares fell more than 70% that day. Nine of 211 patients (about 4%) in the Duravyu arm had vision loss not caused by wAMD, with no such cases in the Eylea arm; a post hoc analysis excluding them claimed non-inferiority.
Why it matters: The report gives both the missed primary endpoint and an interim subgroup non-inferiority claim, letting readers weigh how far non-wAMD vision loss explains the failure.
BioCentury's clinical weekly report shows EyePoint announced Monday that Duravyu (vorolanib intravitreal insert) failed to meet the primary endpoint of non-inferiority to comparator Eylea (aflibercept) in the Phase III LUGANO trial in wet age-related macular degeneration; Tenax also plunged after its Phase III readout in pulmonary arterial hypertension. Both companies lost more than half their market value that week.
Why it matters: Both companies missed Phase III endpoints in the same week, ruling out non-inferiority of Duravyu to Eylea and one Tenax Phase III hypothesis in pulmonary arterial hypertension.
AstraZeneca and HUTCHMED jointly announced that the SAFFRON trial met its primary endpoint: Tagrisso plus Orpathys, compared with platinum-based doublet chemotherapy, achieved statistically significant and clinically meaningful improvements in both PFS and OS. The trial enrolled patients with locally advanced or metastatic NSCLC harboring EGFRm with high MET overexpression or amplification whose disease had progressed on Tagrisso.
Why it matters: The SAFFRON trial met both PFS and OS endpoints, showing benefit over doublet chemotherapy in EGFRm NSCLC with high MET alterations after Tagrisso resistance.
A QuANTUM-First subanalysis found quizartinib maintenance significantly improved overall survival in newly diagnosed FLT3-ITD-positive AML patients who did not undergo allogeneic hematopoietic stem cell transplantation (HR 0.401), with greater benefit in those MRD-negative before maintenance (HR 0.194) and a 3-year survival rate of 89.1%. No OS benefit was observed in patients who had undergone allo-HCT.
Why it matters: Reports OS data for quizartinib maintenance by transplant and MRD status, allowing direct comparison with existing FLT3-ITD-positive AML regimens.
SystImmune (Baili-BioPharmaceutical) announced that its self-developed EGFR/HER3 bispecific ADC iza-bren (BL-B01D1) met the primary endpoint of progression-free survival in the Phase III trial BL-B01D1-301 in non-small cell lung cancer.
Why it matters: The trial met the PFS primary endpoint with an OS benefit trend, offering an alternative to standard therapy for EGFR-TKI-resistant patients.
AstraZeneca announced it will terminate the late-stage eVOLVE-Lung02 trial, which evaluated volrustomig plus chemotherapy versus pembrolizumab plus chemotherapy as first-line treatment for metastatic non-small cell lung cancer with PD-L1 expression below 50%. The safety profile was consistent with the known profiles of each agent alone, with no new safety signals identified. The company did not specify the reason for termination.
Why it matters: The head-to-head failure against first-line pembrolizumab rules out volrustomig replacing or adding to standard therapy in this population.
AstraZeneca announced it is discontinuing the Phase 3 eVOLVE-Lung02 study of Volrustomig, its PD-1/CTLA-4 bispecific antibody, as first-line treatment for non-small cell lung cancer.
Why it matters: Head-to-head with pembrolizumab, the discontinuation rules out replacing pembrolizumab first-line in PD-L1<50% NSCLC.
AstraZeneca announced on August 17 that the phase 3 eVOLVE-Lung02 trial of the PD-1/CTLA-4 bispecific volrustomig plus chemotherapy as first-line treatment for metastatic non-small cell lung cancer did not meet its primary endpoints, and the company will stop the trial. Both co-primary endpoints of PFS and OS were not reached versus pembrolizumab plus chemotherapy.
Why it matters: Head-to-head phase 3 versus pembrolizumab plus chemotherapy missed both PFS and OS, informing design of same-target bispecifics in frontline NSCLC.