Clinical Catch-Up: July 6-10

Clinical Research_Compressed

Everybody seems to be back to work after the U.S. 4th of July holiday. Here’s a look at last week’s clinical trial updates.

COVID-19-Related

Regeneron Pharmaceuticals, with the U.S. National Institute of Allergy and Infectious Diseases (NIAID), is launching Phase III trials of REGN-COV2, the company’s two-antibody cocktail for the treatment and prevention of COVID-19.

There are specifically two trials. A Phase III trial will study if REGN-COV2 can prevent infection in uninfected people who have had close exposure to a COVID-19 patient. The drug has also been advanced into the Phase II/III portion of two adaptive Phase I/II/III trials evaluating the cocktail in treating hospitalized and non-hospitalized patients with COVID-19. A Phase I trial in 30 hospitalized and non-hospitalized patients with COVID-19 received a positive review from the Independent Data Monitoring Committee.

Angion is initiating a Phase II trial of ANG-3777 in COVID-19 patients with acute lung injury in Brazil. ANG-3777 is a small molecule designed to mimic the biological activity of hepatocyte growth factor (HGF), which activates the c-Met cascade of pathways involved in tissue and organ repair.

DURECT Corporation began recruiting patients for its Phase II trial of DUR-928 in hospitalized COVID-19 patients with acute liver or kidney injury. It will enroll about 80 patients. DUR-928 is a first-in-class, small molecule, new chemical entity and an endogenous epigenetic regulator.

Nemechek Technologies indicated that COVID-19 patients have started enrolling in an interventional clinical trial at Hospital Virgen del Carmen in Zarate, Argentina. It will test the effect of transcutaneous auricular vagus nerve stimulation (taVNS) in patients with COVID-19-associated pneumonia. It will use Vitality Smartcable taVNS devices supplied by Nemechek.

Gilead Sciences reported additional data from its Phase III SIMPLE-Severe trial and a real-world retrospective group of patients with severe COVID-19. The trial and study data were for its antiviral drug remdesivir, currently the only approved drug to treat the disease. In the analysis, remdesivir was linked to improved clinical recovery as well as a 62% decrease in the risk of death compared to standard of care. The company notes that it is an important finding that needs to be confirmed in future clinical trials.

Also, the company conducted separate subgroup analyses from the Phase III SIMPLE-Severe trial, including studying its safety and efficacy across different racial and ethnic patients in the U.S. That analysis indicated that these subgroups had similar clinical results as the overall patient population. In addition, Gilead presented new data from its compassionate use program. In that data, 83% of pediatric patients with a broad range of disease severity recovered by the 28th day. Also, 92% of pregnant and postpartum women recovered in the same time frame. No new safety issues were observed.

Non-COVID-19-Related

ObsEva announced topline data from the PRIMROSE 1 and 2 Phase III trials of Yselty (linzagolix) for uterine fibroids. In PRIMROSE 1, the trial met the primary endpoint at week 24. Women that received the drug showed a statistically significant and clinically meaningful decrease in menstrual blood loss compared to placebo. In women receiving 200 mg Yselty with Add Back Therapy (ABT), which is 1 mg estradiol and 0.5 mg norethindrone acetate daily, had a 75.5% responder rate and patients receiving 100 mg of Yselty without ABT had a 56.4% responder rate.

The pooled data from both trials at week 24 support a “best-in-class profile,” the company indicates, with a responder rate of 84.7% in women receiving 200 mg Yselty with ABT and in women receiving 100 mg without ABT, having a 56.4% responder rate.

Also, new data from PRIMROSE 2 demonstrated that continued treatment with the drug for 52 weeks offered sustained efficacy and was well tolerated. In the women receiving 200 mg with ABT, the responder rates were 91.6% and in women receiving 100 mg without ABT, the responder rate was 53.2%. In addition, in both trials, the women receiving Yselty showed statistically significant improvements in a number of secondary endpoints, including a decrease in pain, improvement in anemia and quality of life.

Immunomedics’ Phase III ASCENT trial of Trodelvy (sacituzumab govitecan-hzly) hit its primary endpoint of progression-free survival (PFS) in brain metastasis negative patients with metastatic triple-negative breast cancer (mTNB) who had at least two previous therapies for metastatic disease. It also hit key secondary endpoints. Trodelvy is an antibody-drug conjugate (ADC) directed against Trop-2, a cell-surface protein on many solid tumors.

Merck announced new analyses from the Phase IIb trial of islatravir in combination with Pifeltro (doravirine) in adults with HIV-1 who had not previously received antiretroviral treatment. Islatravir is an oral nucleoside reverse transcriptase translocation inhibitor (NRTTI). The first sub-analysis further described the combinations tolerability and safety profile through Week 48 in three dose levels. The second sub-analysis showed the patients who initiated the combination treat with 3TC and switched to islatravir and doravirine maintained antiviral activity at Week 38.

ORYZON Genomics presented final data from its Phase IIa trial REIMAGINE at the 28th European Congress of Psychiatry, EPA 2020. The data was the final data from the 30 patients in the study, 12 with Borderline Personality Disorder (BPD), 11 with ADHD and 7 with Autism Spectrum Syndrome (ASD). A correlation was observed between the various clinical improvements caused by the drug.

Cellectis announced that the U.S. Food and Drug Administration (FDA) had placed a clinical hold on its MELANI-01 trial. MELANI-01 is a Phase I open-label first-in-human dose escalation study of UCARTCS1A for relapsed or refractory multiple myeloma (MM). UCARETCS1A is an allogeneic, off-the-shelf, gene-edited T-cell therapy designed to treat CS1/SLAMF7-expressing hematologic cancers. CS1 (SLAMF7) is highly expressed on multiple myeloma cancer cells.

The hold was apparently based on a safety issue in one patient enrolled at the study at dose level two (DL2). The patient had r/r multiple myeloma. The patient had been treated previously with several lines of therapy, including autologous CAR T-cells, without success. During this trial, the patient had a fatal treatment-emergent cardiac arrest. The company is continuing to evaluate the clinical data and other details related to the causes of the death.

Apellis Pharmaceuticals completed enrollment in the Phase III DERBY and OAKS trials of intravitreal pegcetacoplan (APL-2), a targeted C3 therapy for geographic atrophy (GA) secondary to age-related macular degeneration (AMD). GA causes blindness. It is a progressive complement-driven eye disease.

Vaccinex indicated it is on track to complete the potentially pivotal SIGNAL trial in Huntington’s disease. Primary efficacy data has been collected from all patients who completed the study except for two whose evaluations were delayed by the pandemic. But the clinical sites are now reopened and the complete efficacy evaluations are expected later this month. The trial is evaluating pepinemab in Huntington’s disease. The drug is a humanized monoclonal antibody that binds and blocks the activity of semaphoring 4D (SEMA4D), an extracellular signaling molecule that regulates the migration and function of immune and inflammatory cells.

Quantum Leap Healthcare Collaborative initiated an investigational treatment arm with Byondis’ [vic-]trastuzumab duocarmazine (SYD985) in the ongoing ISPY-2 Trial for neoadjuvant treatment of locally advanced breast cancer. The treatment arm will focus on HER2 low early-stage breast cancer. It will evaluate if the drug will limit tumor growth in patients whose tumors are not normally treated with HER2-targeted therapies.

Otonomy announced positive topline data from the Phase I/II clinical trial of OTO-313 in patients with persistent tinnitus of at least moderate severity. It demonstrated a positive clinical signal based on a TFI responder analysis, with a favorable safety profile. OTO-313 is a sustained-exposure formulation of the potent and selective N-Methyl-D-Aspartate (NMDA) receptor antagonist gacyclidine.

Sunovion Pharmaceuticals announced topline data from SEP380-201, its Phase II trial of SEP-4199 in bipolar I depression. SEP-4199 is a non-racemic ratio of amisulpride enantiomers with increased potency for serotonin 5-HT7 receptors relative to dopamine D2 receptors. Patients receiving the drug showed numerical improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) total score compared to placebo after six weeks of treatment. However, the study did not meet its primary endpoint.

ViiV Healthcare, an HIV-focused company formed via a partnership of GlaxoSmithKline, Pfizer and Shionogi Limited, presented final data from the HPTN-083 study during AIDS 2020. In the final data, 52 confirmed cases of HIV were observed in the HPTN 083 trial, with 13 cases in the long-acting cabotegravir arm and 39 cases in the daily Truvada arm. The Phase IIb/III trial is evaluating the safety and efficacy of long-acting, injectable cabotegravir for HIV pre-exposure prophylaxis (PrEP) in men who have sex with men (MSM) and transgender women who have sex with men. Cabotegravir was 66% more effective at preventing HIV prevention compared to Gilead Sciences’ Truvada.

ZIOPHARM Oncology dosed the first patient with diffuse intirinsic pontinei glioma (DIPG) in its Phase I/II trial of Ad-RTS-hIL-12 with veledimex. DIPG is a pediatric brain cancer that affects about 4.84 children per 100,000. Ziopharm’s Controlled IL-12 platform is a gene therapy to induce and control the production of human interleukin 12 (hIL-12), a master-regulator of the immune system.

Fate Therapeutics received the FDA greenlight to launch a clinical trial for FT819, an off-the-shelf allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD19- malignancies. It plans to investigate FT819 in patients with relapsed/refractory B-cell malignancies, including chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), and non-Hodgkin lymphoma (NHL).

Biogen published positive results from the Phase I/II trial of tofersen for superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS) in The New England Journal of Medicine. A mutation in the SOD1 gene appears to drive about 2% of all ALS cases. Tofersen is an antisense oligonucleotide (ASO) that binds to SOD1 mRNA, allowing for its degradation by RNase-H.

PTC Therapeutics dosed the first patient in its Phase I trial of PTC857 in healthy volunteers. PTC857 was developed through the company’s Bio-e platform and is a small molecule that inhibits 15-Lipoxygenase. It is being developed first for Parkinson’s disease caused by a mutation in the GBA gene, one of the most common genetic subtypes of Parkinson’s disease.

Bayer’s Phase III FIDELIO-DKD of finerenone added to standard of care for chronic kidney disease (CKD) in patients with type 2 diabetes met its primary endpoint. The drug delayed the progression of CKD by decreasing the combined risk of time to first occurrence of kidney failure greater than or equal to 40% from baseline over at least four weeks, or renal death. Finerenone is a non-steroidal, selective mineralocorticoid receptor antagonist (MRA) shown to decrease the harmful effects of mineralocorticoid receptor (MR) overactivation.

Atox Bio had positive results in its Phase III ACCUTE trial reltecimod for early treatment of severe Necrotizing Soft Tissue Infection (NSTI), a so-called flesh-eating disease. Reltecimod is a synthetic peptide antagonist of both superantigen exotoxins and the CD28 T-cell costimulatory receptor. The drug is designed to modulate the body’s acute inflammatory response, instead of just blocking or inhibiting it. The idea is to assist in controlling the cytokine storm, an immune overreaction, found in NSTI. The data from the trial demonstrated a significant difference in the proportion of patients given reltecimod who achieved resolution of organ dysfunction or failure by Day 14 compared to the percent of patients who received placebo. Resolution of organ dysfunction by Day 14 is seen in the literature and in the trial appeared to have a positive effect on 90-day mortality.

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