Periodic Fever Syndrome

Novartis' canakinumab failed again in non-small cell lung cancer (NSCLC), and Anixa Biosciences, Palisade Bio and Genexine kicked off new trials. For that and more clinical news, keep reading. Novartis reported that its Phase III CANOPY-A trial of canakinumab for adults with NSCLC failed to hit its primary efficacy endpoint. The drug is a human monoclonal antibody targeting interleukin-1ß. The trial evaluated almost 1,400 patients with stage II-IIIA and IIIB NSCLC whose tumors had been completely resected. The primary endpoint was disease-free survival (DFS). Marketed as Ilaris, the drug is indicated for cryopyrin-associated autoinflammatory syndromes in children and adults, systemic juvenile idiopathic arthritis and three other periodic fever syndromes. It is also approved to treat adult-onset Still's disease. Anixa Biosciences treated the first patient at the H. Lee Moffitt Cancer Center & Research Institute with its CAR-T therapy for ovarian cancer. The Phase I dose-escalation study will include 48 patients. The treatment leverages Anixa's chimeric endocrine receptor T-cell (CER-T) because the engineered T-cells target an endocrine receptor. The endocrine receptor target is a follicle-stimulating hormone receptor (FSHR), which is exclusively expressed on ovarian cells in healthy adult females. Palatin Technologies announced a planned interim analysis of its Phase III MELODY-1 trial of PL9643 for dry eye disease. The interim analysis included the independent Data Monitoring Committee (DMC) evaluation of the first 120 patients who completed the treatment. The DMC recommended the trial continue with a study sample size target of 350 patients. No safety concerns were identified. PL9643 is a melanocortin agonist. Palisade Bio dosed the first patient in a Phase III trial of LB1148, which aims to accelerate the return of bowel function in adults undergoing gastrointestinal surgery. The drug is a novel oral liquid formulation of the digestive enzyme inhibitor tranexamic acid. Palisade believes it has the potential to decrease abdominal adhesions and help restore bowel function after surgery. It neutralizes the activity of potent digestive proteases released from the gut during surgery. Genexine dosed the first patient in a Phase II trial of triple combination therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). The treatment consists of two of Genexine's drugs, GX-188E and GX-17. GX-188E is a first-in-class DNA vaccine, while GX-17 is a first-in-class long-acting interleukin 7. The third drug is Bristol Myers Squibb's anti-PD-1 checkpoint inhibitor Opdivo (nivolumab). The study is being run in South Korea and will evaluate the combination in 21 patients with HPV-16 or 18-positive recurrent/metastatic head and neck squamous cell carcinoma. PharmaJet and the University of Adelaide launched a human clinical trial of a DNA-based COVID-19 vaccine booster using the PharmaJet Tropis Needle-free Injection System (NFIS). The vaccine targets the Omicron variant and, as a DNA vaccine, can be modified easily to future variants. The partners chose the PharmaJet Tropis NFIS based on preclinical and clinical data showing improved immunogenicity when administering DNA vaccines. CSL announced positive topline results for its Phase III trial of garadacimab for hereditary angioedema (HAE). The drug is a first-in-class monoclonal antibody inhibiting Factor XIIa. The trial hit the primary and secondary efficacy endpoints and demonstrated a favorable safety profile. HAE is a rare, genetic and potentially life-threatening disease that causes painful, debilitating and unpredictable swelling of the abdomen, larynx, face and extremities. Valo Health dosed the first patient in its Phase II trial of oral OPL-0401 in patients with mild, moderate and severe non-proliferative diabetic retinopathy. OPL-0401 is a small molecule Rho kinase 1/2 inhibitor and a potential first-in-class oral option compared to current intravitreal injections, surgery, or laser treatment options. The study was designed using the company's Opal Computational Platform, allowing real-world data analyses to identify patient populations that might benefit from early treatment. Lundbeck reported that Vyepti (eptinezumab) failed to show statistical superiority over placebo at reducing the number of monthly migraine days. The drug was approved in the United States in 2020 as a preventive measure against migraine. The Phase III Sunlight trial was designed to set the drug up for accelerated approval in China. Sorrento Therapeutics received clearance from the Chinese regulatory authority to initiate a Phase I trial of its oral main viral protease inhibitor, STI-1558, in COVID-19 patients. A single ascending dose (SAD) portion of the trial was completed in Australia with no serious adverse events or severe treatment-emergent adverse events. Pharmacokinetics were dose proportional. In the China trial, the drug will be given to patients with COVID-19 in multiple ascending doses with three dose cohorts.

Novartis’ canakinumab failed again in non-small cell lung cancer while Anixa Biosciences, Palisade Bio and Genexine kicked off new trials. Novartis’ canakinumab failed again in non-small cell lung cancer (NSCLC), and Anixa Biosciences, Palisade Bio and Genexine kicked off new trials. For that and more clinical news, keep reading. Novartis reported that its Phase III CANOPY-A trial of canakinumab for adults with NSCLC failed to hit its primary efficacy endpoint. The drug is a human monoclonal antibody targeting interleukin-1ß. The trial evaluated almost 1,400 patients with stage II-IIIA and IIIB NSCLC whose tumors had been completely resected. The primary endpoint was disease-free survival (DFS). Marketed as Ilaris, the drug is indicated for cryopyrin-associated autoinflammatory syndromes in children and adults, systemic juvenile idiopathic arthritis and three other periodic fever syndromes. It is also approved to treat adult-onset Still’s disease. Anixa Biosciences treated the first patient at the H. Lee Moffitt Cancer Center & Research Institute with its CAR-T therapy for ovarian cancer. The Phase I dose-escalation study will include 48 patients. The treatment leverages Anixa’s chimeric endocrine receptor T-cell (CER-T) because the engineered T-cells target an endocrine receptor. The endocrine receptor target is a follicle-stimulating hormone receptor (FSHR), which is exclusively expressed on ovarian cells in healthy adult females. Palatin Technologies announced a planned interim analysis of its Phase III MELODY-1 trial of PL9643 for dry eye disease. The interim analysis included the independent Data Monitoring Committee (DMC) evaluation of the first 120 patients who completed the treatment. The DMC recommended the trial continue with a study sample size target of 350 patients. No safety concerns were identified. PL9643 is a melanocortin agonist. Palisade Bio dosed the first patient in a Phase III trial of LB1148, which aims to accelerate the return of bowel function in adults undergoing gastrointestinal surgery. The drug is a novel oral liquid formulation of the digestive enzyme inhibitor tranexamic acid. Palisade believes it has the potential to decrease abdominal adhesions and help restore bowel function after surgery. It neutralizes the activity of potent digestive proteases released from the gut during surgery. Genexine dosed the first patient in a Phase II trial of triple combination therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). The treatment consists of two of Genexine’s drugs, GX-188E and GX-17. GX-188E is a first-in-class DNA vaccine, while GX-17 is a first-in-class long-acting interleukin 7. The third drug is Bristol Myers Squibb’s anti-PD-1 checkpoint inhibitor Opdivo (nivolumab). The study is being run in South Korea and will evaluate the combination in 21 patients with HPV-16 or 18-positive recurrent/metastatic head and neck squamous cell carcinoma. PharmaJet and the University of Adelaide launched a human clinical trial of a DNA-based COVID-19 vaccine booster using the PharmaJet Tropis Needle-free Injection System (NFIS). The vaccine targets the Omicron variant and, as a DNA vaccine, can be modified easily to future variants. The partners chose the PharmaJet Tropis NFIS based on preclinical and clinical data showing improved immunogenicity when administering DNA vaccines. CSL announced positive topline results for its Phase III trial of garadacimab for hereditary angioedema (HAE). The drug is a first-in-class monoclonal antibody inhibiting Factor XIIa. The trial hit the primary and secondary efficacy endpoints and demonstrated a favorable safety profile. HAE is a rare, genetic and potentially life-threatening disease that causes painful, debilitating and unpredictable swelling of the abdomen, larynx, face and extremities. Valo Health dosed the first patient in its Phase II trial of oral OPL-0401 in patients with mild, moderate and severe non-proliferative diabetic retinopathy. OPL-0401 is a small molecule Rho kinase 1/2 inhibitor and a potential first-in-class oral option compared to current intravitreal injections, surgery, or laser treatment options. The study was designed using the company’s Opal Computational Platform, allowing real-world data analyses to identify patient populations that might benefit from early treatment. Lundbeck reported that Vyepti (eptinezumab) failed to show statistical superiority over placebo at reducing the number of monthly migraine days. The drug was approved in the United States in 2020 as a preventive measure against migraine. The Phase III Sunlight trial was designed to set the drug up for accelerated approval in China. Sorrento Therapeutics received clearance from the Chinese regulatory authority to initiate a Phase I trial of its oral main viral protease inhibitor, STI-1558, in COVID-19 patients. A single ascending dose (SAD) portion of the trial was completed in Australia with no serious adverse events or severe treatment-emergent adverse events. Pharmacokinetics were dose proportional. In the China trial, the drug will be given to patients with COVID-19 in multiple ascending doses with three dose cohorts.

Courtesy of Taljat David/Shutterstock On Monday, Novartis released results from the Phase III CANOPY-A trial, showing that its candidate canakinumab (ACZ885) failed to meet its primary efficacy endpoint in adult non-small cell lung cancer (NSCLC) patients. CANOPY-A, a multicenter, randomized and double-blind study, enrolled nearly 1,400 patients with stage II-IIIA and IIIB disease whose tumors had been completely resected. Canakinumab was given at 200-mg subcutaneous doses every three weeks, and its efficacy was compared to placebo. CANOPY-A’s primary endpoint was disease-free survival (DFS). While canakinumab was unable to demonstrate superior DFS to placebo, it nevertheless showed a good tolerability pro induced no unexpected safety signals. “While we are disappointed CANOPY-A did not show the benefit we hoped for, every trial generates scientific evidence that supports future research and development, and we look forward to continuing to pursue new therapeutic options for people living with lung cancer, whose needs remain urgent and significant,” Jeff Legos, executive vice president and global head of oncology & hematology development at Novartis, said in a statement. The company is scheduled to present these findings at an upcoming medical conference. Canakinumab is a human monoclonal body designed to target interleukin-1β with high affinity and selectivity, in turn preventing it from activating its downstream receptors. This mode of action makes canakinumab an effective anti-inflammatory molecule and has helped it win approvals from the FDA. In 2009, Novartis’s Ilaris (canakinumab) was given the go-ahead for the treatment of Cryopyrin-Associated Autoinflammatory Syndromes in both children and adults. The drug continued to pick up regulatory nods in the years following, receiving approvals for Systemic Juvenile Idiopathic Arthritis in 2013 and three other periodic fever syndromes in 2016. Most recently, in 2020, the FDA awarded Ilaris its greenlight for Adult-Onset Still’s Disease. A Tough Time for Canakinumab In 2011, the pharma powerhouse also launched its CANTOS program, which looked at the potential of canakinumab in cardiovascular disease. As the study was nearing its end, in 2017, Novartis saw that their drug slashed lung cancer incidence in their patient population by 67% and related deaths by 77%. This led Novartis to start its four-trial CANOPY program in the hopes of launching canakinumab in the oncology space. After all, the action against interleukin-1β also suppresses pro-tumor inflammation, boosts the immune response against tumors and disrupts angiogenesis. “We made an investment in the CANOPY program based on signals of reduced lung cancer incidence and mortality observed in the CANTOS study. These positive signals supported the study of canakinumab as adjuvant treatment for early lung cancer,” Legos said. But this path has been disappointing for Novartis. In March 2021, canakinumab failed in the CANOPY-2 Phase III NSCLC trial when it fell short of yielding significantly better overall survival than docetaxel monotherapy in more than 200 patients with locally advanced or metastatic disease. CANOPY-1, another NSCLC trial for canakinumab, fell soon after. Later that year, in October, the drug was unable to demonstrate meaningful improvements in overall and progression-free survival when combined with Merck’s checkpoint inhibitor Keytruda (pembrolizumab) and a platinum-based regimen. Only one trial remains under the CANOPY program: CANOPY-N, which looks at the drug’s potential as a neoadjuvant intervention. The readout is expected in the coming week.