Clinical Catch-Up: November 9-13
It was a particularly busy week for clinical trial updates, mostly because of several virtual conferences, including the virtual American Heart Association (AHA) Scientific Sessions 2020 and The Society for Immunotherapy of Cancer’s Annual Meetings (SITC 2020). Here's a look.
COVID-19-Related
Pfizer and BioNTech announced their COVID-19 vaccine was more than 90% effective in preventing COVID-19 in the first interim efficacy analysis. It evaluated 94 confirmed COVID-19 cases in trial participants. Although those numbers may go down over time, it is excellent news in general for the vaccine, and, as Pfizer chairman and chief executive officer said, “Today is a great day for science and humanity.” The data found the 90% efficacy rate at 7 days after the second dose, suggesting that protection is achieved 28 days after initiation of the vaccine, which has a 2-dose schedule. No serious safety concerns were observed.
Moderna has indicated they are projected to have data to report by the end of the month on their COVID-19 vaccine program. They said they needed 53 patients in the study to be diagnosed with COVID-19, and the trial hit that figure Wednesday, November 11. At this time the data is blinded so they don’t know yet if the sick patients received the vaccine or the placebo, but they are preparing the data for the Data and Safety Monitoring Board (DSMB).
Arcturus Therapeutics announced positive interim data from its ongoing Phase I/II trial of ARCT-021, its vaccine against COVID-19. It is being developed in collaboration with Duke-NUS Medical School. ARCT-021 combines self-transcribing and replicating mRNA (STARR) with LUNAR lipid-mediated delivery technology.
Novavax indicated the FDA had granted its COVID-19 vaccine candidate, NVX-CoV2373, Fast Track Designation. It is currently in Phase III development, with a trial expected to begin by the end of November in the U.S. and Mexico and its UK trial expected to be fully enrolled by the end of the month.
INmune Bio dosed the first patient in its Phase II trial of Quellor for pulmonary complications from COVID-19. Quellor is a selective soluble Tumor Necrosis Factor (sTNF) inhibitor.
CureVac NV, located in Tübingen, Germany, published detailed interim Phase I data of its COVID-19 vaccine candidate, CVnCoV. The manuscript is currently on medRxiv and will be submitted to a peer-reviewed scientific journal. The Phase I study was in healthy volunteers between the ages of 18 and 60 years. The interim analysis demonstrated that two doses of the vaccine ranging from 2 micrograms to 12 micrograms per dose, given 28 days apart, were safe, with no vaccine-related serious adverse events. However, the higher the dose, the more likely to be numerically more systemic adverse events and were more severe; to a lesser extent, local reactions also increased with higher doses. The side effects were mild or moderate and transient in nature.
In addition, they analyzed immune responses by measuring IgG antibodies against the S protein or its receptor-binding domain (RBD) and SARS-CoV-2-virus neutralizing antibodies. They found the immune responses increased as the dose increased and showed the seroconversion two weeks after the second vaccination was about 4-fold over baseline titer in the 12-microgram doses. The immune response was comparable to the immune responses in COVID-19 patients who recovered from the disease.
Medicago reported positive interim data for its Phase I COVID-19 vaccine trial. They reported 100% of subjects developed a promising antibody response after two doses of the adjuvanted vaccine candidate.
TriNetX published clinical research data based on real-world evidence (RWE) citing an increased risk of adverse mental health consequences in people diagnosed with COVID-19 and that having a psychiatric disorder increases the risk of getting COVID-19. The research was conducted by the University of Oxford.
Russia’s National Research Center for Epidemiology and Microbiology announced that the Sputnik V vaccine against COVID-19 had an efficacy rate of 92% after the second dose. This was an apparent announcement from an interim analysis of its ongoing Phase III trial.
Mesoblast Limited announced that its Phase III trial of remestemcel-L in patients with moderate to severe ARDS due to COVID-19 got a recommendation to proceed after the second interim analysis. It was performed on the first 135 patients, 45% of the planned 300.
AstraZeneca reported that the CALAVI Phase II trials of Calquence (acalabrutinib) in hospitalized patients with respiratory symptoms of COVID-19 failed to meet the trials’ primary efficacy endpoint. Calquence is the company’s next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK), which is otherwise being developed for multiple B-cell blood cancers by AstraZeneca and Acerta Pharma. The CALAVI Phase II program is made up of two trials of Calquence with best supportive care (BSC) compared to BSC alone in patients hospitalized with respiratory complications of COVID-19.
Organicell Regenerative Medicine provided an update on its Phase I/II trial of Zofin for COVID-19. So far, several patients have been enrolled, dosed and treated. They expect enrollment and for the trial to complete by December 31, 220, and if the results are favorable, to begin Phase IIb in the first quarter of 2021.
Washington University School of Medicine in St. Louis published the results of a clinical trial evaluating an antidepressant, fluvoxamine, for early treatment for COVID-19. Fluvoxamine, which is a generic, but sometimes sold under the brand name Luvox, is a member of the class of drugs known as selective serotonin reuptake inhibitors (SSRIs). The trial evaluated whether taking fluvoxamine within seven days of first symptoms of COVID-19 can decrease the risk of respiratory deteriorating. The study showed the drug was effective—none of the 80 patients receiving the drug hit the respiratory deteriorating criteria compared to the 8.3% rate in the 72 patients in the placebo cohort.
Non-COVID-19-Related
Axovant Gene Therapies, now Sio Gene Therapies, got the go-ahead from the FDA to lift the clinical hold to initiate a trial of AXO-AAV-GM2 gene therapy to treat patients with Tay-Sachs disease and Sandhoff disease. It is the first investigational gene therapy given IND clearance for those two diseases.
ViiV Healthcare announced that a DSMB recommended they unblind the data early from their HIV Prevention Trials Network (HPTN) 084 trial of cabotegravir for HIV prevention in women. The pre-specified interim data analysis indicated the drug hit the primary objective of superiority compared to the current standard of care for women, which was daily oral emtricitabine/tenofovir disoproxil fumarate 200 mg and 300 mg (FTC/TDF) tablets (Gilead Sciences’ Truvada). Cabotegravir was 89% more effective than the daily FTC/TDF for pre-exposure prophylaxis (PrEP).
Reata Pharmaceuticals’ Phase III CARDINAL trial of bardoxolone methyl in chronic kidney disease caused by Alport syndrome hit its primary and key secondary endpoints at the end of Year 2. This included estimated glomerular filtration rate values for patients who either remained on or discontinued the drug at Week 100 showed the patients receiving bardoxolone had a statistically significant improvement compared to placebo in mean change from baseline in eGFR.
Repertoire Immune Medicines announced preliminary clinical and biomarker data from its Phase I/II trial of PRIME IL-15 cell therapy (RPTR-147) in advanced metastatic solid tumors. PRIME IL-15 is a novel autologous, non-genetically modified multi-clonal T-cell therapy loaded with an IL-15Fc nanogel designed to release IL-15 in a local and sustained manner.
Calliditas Therapeutics reported positive topline results from Part A of its Phase III NeflgArd trial of Nefecon in patients with primary IgA nephropathy (IgAN). It demonstrated statistically significant reduction in urine protein creatinine ratio, UPCR or proteinuria, after nine months of Nefecon treatment compared to placebo. Nefecon is a patented oral formulation of budesonide for targeted release.
Exicure presented updated Phase Ib data from its ongoing Phase Ib/II trial of intratumoral cavrotolimod (AST-008) in combination with checkpoint inhibitors Keytruda or Libtayo in patients with Merkel cell carcinoma, cutaneous squamous cell carcinoma, and other advanced solid tumors. AST-008 is an SNA-enabled TLR9 agonist.
Genocea Biosciences shared expanded clinical and immunogenicity findings from Part B of its ongoing GEN-009 Phase I/IIa trial of GEN-009 in combination with checkpoint inhibitors in advanced cancers. GEN-009 is a neoantigen vaccine.
Adavaxis presented data from its ongoing Phase I/II trial of ADXS-503 as a monotherapy and in combination with Merck’s checkpoint inhibitor Keytruda (pembrolizumab) in non-small cell lung cancer (NSCLC). ADXS-503 is the first drug from its ADXS-HOT off-the-shelf, cancer-type specific, immunotherapy program that uses the company’s Lm technology platform to target hotspot mutations.
Cue Biopharma presented data from its CUE-101 in recurrent/metastatic HPV16+ head and neck cancer. CUE-101 is in a Phase I trial. It is a novel HPV16 E7-pHLA-IL2-Fc fusion protein.
Checkpoint Therapeutics announced updated interim results from its ongoing Phase I trial of cosibelimab in advanced cancers, including a cohort of previously untreated patients with high PD-L1 expressing advanced NSCLC. Cosibelimab is an anti-PD-L1 checkpoint inhibitor.
Intellia Therapeutics dosed the first patient with NTLA-2001 in its Phase I trial of transthyretin amyloidosis (ATTR) with polyneuropathy (hATTR-PN). NTLA-2001 is a CRISPR therapy designed to be administered systemically to edit genes inside the body. Its non-viral platform leverages lipid nanoparticles designed to deliver a two-part genome editing system to the liver.
Amgen and AstraZeneca announced that their Phase III NAVIGATOR trial of Tezepelumab hit the primary endpoint in severe asthma. The drug with standard of care demonstrated a statistically significant and clinically meaningful decrease in the annualized asthma exacerbation rate (AAER) over 52 weeks compared to placebo plus standard of care. Tezepelumab is a potential first-in-class human monoclonal antibody that targets and blocks thymic stromal lymphopoietin (TSLP), a key epithelial cytokine.
Merck and Eisai’s Phase III KEYNOTE-581/CLEAR trial of Eisai’s Lenvima (lenvatinib) and Merck’s checkpoint inhibitor Keytruda (pembrolizumab) had positive topline results for advanced renal cell carcinoma (RCC). Levima is a kinase inhibitor. The combo was also evaluated against sunitinib (Pfizer’s Sutent, also a tyrosine kinase inhibitor). The primary endpoint was progression-free survival.
Agenus advanced MK-4830 into Phase II for advanced solid tumors. MK-4830 is an ILT4 antibody, which it licensed to Merck.
Oryzon Genomics received approval from the Spanish Drug Agency (AEMPS) to conduct a Phase IIb trial of vafidemstat in patients with Borderline Personality Disorder (BPD). Vafidemstat is an oral, CNS optimized LSD1 inhibitor.
Oryzon Genomics also presented preliminary safety and efficacy data of one of its ongoing Phase IIa trials of iadademstat, ALICE, in acute myelogenous leukemia (AML). The patients received the drug in combination with azacytidine and focused on elderly patients. Iadademstat is a small oral molecule that acts as a highly selective LDS1 inhibitor.
Verrica Pharmaceuticals announced positive topline data in Phase II trial of VP-102 in external genital warts. VP-102is a novel topical therapy containing a solution of 0.7% cantharidin in a proprietary single-use applicator.
Immunophotonics dosed the first patient in the Phase Ib/IIa trial of IP-001 in thermally ablated solid tumors. IP-001 is a proprietary carbohydrate polymer intended to trigger a tumor-specific immune response when exposed to tumor antigens liberated by ablation.
Arena Pharmaceuticals completed its Phase I trial of APD418 and plans to initiate a Phase II in 2021. The drug is being evaluated for acute heart failure. The company also reported that its S1P inhibitor etrasimod, missed the primary endpoint in its Phase II trial for atopic dermatitis. But they plan on continuing with a Phase III trial.
Adaptimmune Therapeutics presented data from the dose escalation cohorts of its Phase I SURPASS trial of ADP-A2M4CD8. In the cohorts of heavily pre-treated advanced cancer patients, three received target doses of 1 billion SPEAR T-cells and three with 4 billion. There were two confirmed partial responses, one in an esophagogastric junction (EGJ) cancer patient, and one in a patient with head and neck cancer.
EIP Pharma presented full results of the Phase II AscenD-LB trial in patients with mild-to-moderate dementia with Lewy bodies (DLB). The study met the primary endpoint, demonstrating significant, clinically relevant effect size improvement in cognition in patients receiving neflamapimod 40mg three times a day compared to placebo or neflamapimod 40mg twice a day. Neflamapimod is a brain-penetrant, oral small molecule inhibitor of the intra-cellular enzyme p38 MAP kinase alpha, which is expressed in neurons under conditions of stress and disease.
Onxeo SA completed enrollment in the DRIIV-Ib study of AsiDNA in combination with carboplatin and paclitaxel in advanced solid tumors. AsiDNA is the first compound from the company’s platoon, a first-in-class, highly differentiated DNA Damage Response (DDR) inhibitor based on a decoy and agonist mechanism that acts upstream of multiple DDR pathways.
Amylyx Pharmaceuticals completed treatment of the planned 24 weeks in the Phase II PEGASUS trial of AMX0035 in Alzheimer’s disease. AMX0035 is targets endoplasmic reticulum and mitochondrial dependent neuronal degeneration pathways in ALS, Alzheimer’s and other neurodegenerative diseases, and is designed to decrease neuronal death and dysfunction.
Moderna released interim data from the expansion cohort of its ongoing Phase I trial of its mRNA personalized cancer vaccine, mRNA-4157. The product is being tested in combination with Merck’s checkpoint inhibitor Keytruda (pembrolizumab). They presented the data at The Society for Immunotherapy of Cancer’s Annual Meetings (SITC 2020).
The cohort included 10 patients with HPV(-) Head and Neck Squamous Cell Carcinoma (HNSCC) and 17 with Micro-Satellite Stable Colorectal Cancer (MSS-CRC). They found that, in the data obtained so far, the vaccine with Keytruda was well tolerated at all doses and appeared to shrink tumor size based on RECIST 1.1 criteria in the HPV(-) HNSCC patients. No responses were seen in the MSS-CRC group.
Istari Oncology announced Phase I data from its PVSRIPO for patients with anti-PD-1 refractory melanoma. PVSRIPO is a novel immunotherapy made up of a non-neurovirulent rhinovirus:poliovirus chimera. It activates innate and adaptive immunity. In the six patients who received PVSRIPo injections without any other concomitant therapy, the OR was 67%.
Cynata Therapeutics initiated its Phase III SCUlpTOR Trial of CYP-004 for osteoarthritis. Cymerus is a mesenchymal stem cell product. It uses induced pluripotent stem cells (iPSCs) and a precursor cell called mesenchymoangioblast (MCA) for economic manufacture of cell therapy products.
Oncternal Therapeutics updated interim clinical data from its ongoing Phase I trial of TK216 in r/r Ewing sarcoma. TK216 is a potentially first-in-class, targeted small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins.
ImCheck Therapeutics presented preliminary data from its ongoing EVICTIon Phase I/IIa trial of ICT01 in r/r cancers. The data was from the first cohort of six solid tumor cancer patients who received ICT01 alone. ICT01 is a first-in-class gamma delta T cell-activating monoclonal antibody.
Gyroscope Therapeutics dosed the first patient in its Phase II HORIZON trial of gene therapy GT005 in dry age-related macular degeneration. The therapy is a one-time AAV-based gene therapy engineered to restore balance to an overactive complement system by increasing production of the Complement Factor I (CFI) protein.
Zai Lab and Five Prime Therapeutics announced positive topline data from its Phase II FIGHT trial. The trial compared bemarituzumab in combination with mFOLFOX6 chemotherapy to placebo in combination with mFOLFOX6 in patients with FGFR2b+, HER2- frontline advanced gastric or gastroesophageal junction (GEJ) cancer. Bemarituzumab is a potential first-in-class targeted therapy that blocks fibroblast growth factors (FGFs) from binding and activating FGFR2b.
Janssen Pharmaceutical, a Johnson & Johnson company, made 10 data presentations at the virtual American Heart Association (AHA) Scientific Sessions 2020, with four including new sub-analyses of Xarelto (rivaroxaban) from the VOYAGER PAD trial. The company submitted an sNDA to the FDA on October 26 to expand use of Xarelto in patients with peripheral artery disease (PAD) to include decreasing the risk of major thrombotic vascular events, such as heart attack and amputation, in symptomatic patients with recent lower-extremity revascularization (LER).
Apollomics received the go-ahead from China’s regulatory authorities to initiate the Phase I trial of APL-102 in patients with advanced solid tumors. APL-102 is an oral, multi-kinase inhibitor that targets several key oncogenic drivers, both receptor tyrosine kinase (RTKs) and serine/threonine-kinases, including VEGFRs and PDGFRs, MAPK via B-RAF and C-RAF, RET, CSF1R, DDR1 and c-KIT.
RhoVac published the results of its Phase I/II clinical trial of RV001 in patients who had previously undergone radical prostatectomy. The drug is based on a method for antigen-based T-cell activation, but adds a new target protein, RhoC. The trial demonstrated the drug had a long-lasting immune response in the vast majority of patients.
DURECT Corporation presented additional safety data and efficacy signals from its Phase Ib trial of DUR-928 in NASH. In addition to the safety signals, it also indicated improvements in multiple biomarkers of liver health such as a significant decrease in cytokeratin-18 in patients who had a least a 10% reduction in liver fat.
Esperion announced pooled data from four of its Phase III trials of Nexletol (bempedoic acid) by week 12 in specific subgroups, include people who can’t tolerate statins and females, compared to placebo. The drug was approved earlier this year. It is the first oral, once-daily, non-statin LDL-C-lowering drug.
Akero Therapeutics presented additional data from the Phase IIa BALANCED trial of efruxifermin (EFX) as a foundational monotherapy for NASH. The data showed large magnitudes of decrease in liver fat across all EFX dose groups with 100% of patients in the 50mg-dose group achieving more than 50% relative reduction in liver fat and 53% of patients in the same dose group achieving greater than 70% relative reduction in liver fat.
Albireo Pharma announced new data in progressive familial intrahepatic cholestasis (PFIC) that confirmed statistically significant reductions in serum bile acids and improvements in pruritus for odevixibat. Odevixibat is the company’s once-daily, non-systemic ileal bile acid transport inhibitor (IBATi). The data is from the company’s Phase III trial.
NGM Biopharmaceuticals announced data from its Phase I trial of NGM621 in geographic atrophy (GA). The drug is an anti-complement C3 antibody.
Oyster Point Pharma reported positive topline data from the ONSET-2 Phase III trial of OC-01 (varenicline) nasal treatment for dry eye disease. The company plans to submit a NDA to the FDA in the fourth quarter.