Jun 18, 2024
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Takeda revealed topline results from its SKYLINE and SKYWAY studies. SKYLINE (TAK-935-3001) was a multicenter, randomized, double-blind Phase III trial assessing soticlestat (TAK-935) plus standard care against placebo plus standard care in patients with refractory Dravet syndrome. Soticlestat narrowly missed the primary endpoint of reducing convulsive seizure frequency from baseline compared to placebo (p-value = 0.06). However, in the six key secondary endpoints, soticlestat demonstrated clinically meaningful and nominally significant outcomes in the responder rate, caregiver and clinician global impression of improvement measures, and seizure intensity and duration scales over the 16-week treatment period (all p-values ≤ 0.008).
SKYWAY (TAK-935-3002) was a multicenter, randomized, double-blind Phase III trial that assessed the effectiveness of soticlestat in combination with standard care versus placebo with standard care in patients with refractory Lennox-Gastaut syndrome (LGS). Soticlestat did not achieve the primary goal of reducing the frequency of Major Motor Drop (MMD) seizures compared to the placebo.
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In both the SKYLINE and SKYWAY studies, certain predefined patient subgroups showed statistically significant treatment effects on primary and secondary endpoints, including caregiver and clinician global impressions of improvement, as well as scales measuring seizure intensity and duration over the 16-week treatment period. Further analyses are underway. Soticlestat was generally well tolerated in both studies, exhibiting a safety profile consistent with earlier findings.
Takeda will consult with regulatory authorities to review all data from these studies and decide on the next steps. Additionally, Takeda plans to present the results from both Phase III studies at a forthcoming scientific congress.
Takeda is also evaluating the financial implications of the study results, including potential impairment losses on intangible assets, for the first quarter ending June 30, 2024, and will provide updates as needed promptly.
AstraZeneca’s Imfinzi (durvalumab), when combined with carboplatin and paclitaxel and followed by Imfinzi as a monotherapy, has been approved in the US for treating adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR).
The FDA granted approval based on a prespecified exploratory subgroup analysis by MMR status from the DUO-E Phase III trial, with results published in the Journal of Clinical Oncology.
In this trial, the combination of Imfinzi with carboplatin and paclitaxel, followed by Imfinzi alone (Imfinzi arm), reduced the risk of disease progression or death by 58% in patients with dMMR endometrial cancer compared to chemotherapy alone (hazard ratio 0.42; 95% confidence interval 0.22-0.80).
Dave Fredrickson, Executive Vice President of the Oncology Business Unit at AstraZeneca, stated: “Over the past few decades, there have been few advancements in endometrial cancer treatment, making ongoing innovation essential as the incidence of this cancer is anticipated to increase. The combination of immunotherapy and chemotherapy is becoming a new standard of care in this area, and the approval of Imfinzi provides a significant new treatment option for patients with mismatch repair deficient disease.”
The safety and tolerability profile of the Imfinzi and chemotherapy regimen was generally manageable and consistent with previous clinical trials, showing no new safety concerns.
The combination of Lynparza (olaparib) and Imfinzi, which involved Imfinzi plus chemotherapy followed by maintenance therapy with Imfinzi and Lynparza, also achieved the primary endpoint of progression-free survival (PFS). The trial is ongoing to evaluate overall survival as a key secondary endpoint for both treatment arms. Regulatory applications for the Imfinzi and the combined Imfinzi and Lynparza regimens are currently under review in the EU, Japan, and several other countries based on the DUO-E results.
Johnson & Johnson has announced that patients treated with nipocalimab showed a statistically significant (P=0.002) and clinically meaningful improvement in ClinESSDAIa scores compared to a placebo at 24 weeks, based on baseline measurements. This was the primary endpoint in the Phase 2 DAHLIAS dose-ranging study involving adult patients with Sjögren’s disease. Improvements were seen as early as Week 4 and continued to grow over the 24-week treatment period compared to those receiving the placebo. These findings mark the first positive results for nipocalimab in treating SjD. The study results were highlighted in a late-breaking presentation (LBA0010) and are part of the 30 abstracts Johnson & Johnson is presenting at the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress.
“These data provide proof of concept for nipocalimab in treating Sjögren’s disease and support further clinical development, which is promising news for the approximately four million people worldwide affected by this chronic, debilitating condition,” said Prof. Jacques-Eric Gottenberg, M.D., Ph.D., from the Department of Rheumatology at Strasbourg University Hospital, National Centre for Rare Systemic Autoimmune Diseases, and study investigator. “Patients with Sjögren’s disease need approved advanced therapies to address the serious health consequences of the disease, and I am encouraged by these results and the positive impact on clinically meaningful disease measures.”
In addition to reaching the primary endpoint, the group treated with 15 mg/kg of nipocalimab showed:
Bristol Myers Squibb has announced that the FDA has granted accelerated approval for Augtyro™ (repotrectinib) for treating adults and children aged 12 and older with solid tumors featuring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. This approval applies to patients whose tumors are locally advanced or metastatic, or where surgical resection would likely cause severe morbidity, and who have either progressed following treatment or have no satisfactory alternative therapy. The decision is based on the results from the Phase I/II TRIDENT-1 study, which assessed Augtyro in adult patients with NTRK-positive solid tumors. This indication received accelerated approval based on the overall response rate and duration of response, with continued approval dependent on the verification and description of clinical benefit in confirmatory trials.
The TRIDENT-1 trial enrolled patients with NTRK-positive locally advanced or metastatic solid tumors, encompassing 15 different types of cancer, including both those who had not received prior TKI treatment (n=40) and those who had (n=48). In TKI-naïve patients, after a median follow-up of 17.8 months, 58% (95% CI: 41 to 73) achieved a confirmed objective response rate (cORR). Among these responders, 43% achieved partial responses (PR), and 15% achieved complete responses (CR). The majority (83%) of TKI-naïve responders maintained their response at one year with Augtyro, and the median duration of response (mDOR) had not been reached.
For TKI-pretreated patients, after a median follow-up of 20.1 months, the cORR was 50% (95% CI: 35 to 65), with 50% achieving PR and none achieving CR. Among TKI-pretreated responders, 42% remained in response at one year with Augtyro. The median duration of response (mDOR) was 9.9 months (95% CI: 7.4 to 13.0).
In patients with measurable central nervous system (CNS) metastases at the start of the trial, two out of two TKI-naïve patients and three out of three TKI-pretreated patients showed an intracranial response.
Based on data from clinical trials and how the drug is processed in the body, the recommended dose of Augtyro for pediatric patients aged 12 years and older matches that for adults. This involves taking 160 mg by mouth once daily for 14 days, followed by 160 mg twice daily until the disease either progresses or intolerable side effects occur. The safety and effectiveness of Augtyro have not been confirmed in children under 12 years old who have solid tumors with an NTRK gene fusion. This marks the second approved use of Augtyro in the United States, following its full approval in November 2023 for treating adult patients with locally advanced or metastatic ROS1-positive NSCLC.
AstraZeneca’s Farxiga (dapagliflozin) has received FDA approval for enhancing blood sugar management in children aged 10 years and above who have type-2 diabetes. This decision by the FDA was supported by promising outcomes from the Phase III T2NOW trial in pediatric patients. Previously, Farxiga was approved in the United States for adults with T2D as an additional treatment alongside diet and exercise to improve blood sugar control.
Ruud Dobber, Executive Vice President of AstraZeneca’s BioPharmaceuticals Business Unit, remarked that the incidence of type-2 diabetes among children and adolescents is increasing. He noted that treatment options in oral form have been scarce for this group. Dobber emphasized that the recent approval is a significant achievement for young patients with type-2 diabetes in the US. He highlighted that this approval expands the potential benefits of the medication to more patients with significant medical needs, underscoring AstraZeneca’s dedication to advancing innovative treatments in cardiovascular, renal, and metabolic diseases.
Data from the T2NOW Phase III trial, published in The New England Journal of Medicine Evidence, showed that Farxiga led to a significant decrease in A1C levels, which indicate average blood sugar, compared to a placebo. The adjusted average reduction in A1C was -0.62% with Farxiga versus an increase of +0.41% with placebo, resulting in a difference of -1.03% (95% CI: -1.57 to -0.49; p<0.001). These findings were statistically significant for the primary and all secondary endpoints compared to placebo at week 26. The results demonstrate that Farxiga can bring clinically meaningful improvements in blood sugar control for children and adolescents with type 2 diabetes. The safety outcomes in this group were similar to those observed in adults with type 2 diabetes, aligning with Farxiga’s well-established safety profile.
Forxiga has also been authorized for children aged 10 years and older with type 2 diabetes in 56 countries, such as the EU and other areas, following findings from the T2GO Phase III clinical trial. Further regulatory submissions and deployment strategies are being assessed pending additional market evaluations.
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