Trial Results

Realm Therapeutics Completes Enrollment in Study for Atopic Dermatitis

June 4, 2018

Realm Therapeutics announced that the Company has completed enrollment in its Phase II study of PR022, Realm’s first-in-class topical IL-4 / IL-13 inhibitor, for the treatment of Atopic Dermatitis. The trial is being conducted in the U.S. The Phase II study is a randomized, double-blind, vehicle-controlled, multicenter, parallel-group study assessing the safety and efficacy of multiple doses of PR022 in 122 adult patients with mild-to-moderate Atopic Dermatitis. Multiple endpoints are being explored, including Eczema Area and Severity Index (EASI), an investigator-assessed tool used to measure the extent (area) and severity of atopic eczema; Investigator Global Assessment (IGA), an investigator-assessed instrument measuring severity of Atopic Dermatitis on a 5 grade scale; as well as additional assessments of pruritus and quality of life. In pre-clinical models of Atopic Dermatitis, PR022 has shown immunomodulatory effects, without the same immunosuppressive side effects often associated with steroids, which are the current standard of care.

Nabriva Therapeutics Announces Positive Topline Results for Treatment of Bacterial Pneumonia

May 29, 2018

Nabriva Therapeutics announced positive topline results from its Lefamulin Evaluation Against Pneumonia (LEAP 2) clinical trial. In LEAP 2, lefamulin met the U.S. Food and Drug Administration (FDA) primary endpoint of non-inferiority (NI, 10.0 percent margin) compared to moxifloxacin for early clinical response (ECR)-assessed 72 to 120 hours following initiation of therapy in the intent to treat (ITT) patient population. Lefamulin also met the European Medicines Agency (EMA) primary endpoint for non-inferiority (NI, 10.0 percent margin) compared to moxifloxacin based on an investigator assessment of clinical response. LEAP 2 was a global, randomized, double-blind, double-dummy trial that compared the efficacy and safety of 600 mg of oral lefamulin twice a day for 5 days versus 400 mg of oral moxifloxacin once daily for 7 days in 738 patients (370 in the lefamulin arm and 368 in the moxifloxacin arm). The lefamulin arm enrolled 183 (49.5 percent), 145 (39.2 percent) and 40 (10.8 percent) patients with a Pneumonia Outcomes Research Team (PORT) class of 2, 3 and 4, respectively. The moxifloxacin arm enrolled 189 (51.4 percent), 133 (36.1 percent) and 42 (11.4 percent) patients with a PORT class of 2, 3 and 4, respectively.

Lilly’s Galcanezumab Meets Primary Endpoint in Phase III Study

May 21, 2018

Eli Lilly and Company announced that galcanezumab met its primary endpoint in a Phase III study of patients with episodic cluster headache, demonstrating statistically significant differences in the reduction of weekly cluster headache attacks compared to placebo across weeks one to three of the two-month, double-blind treatment period. The episodic cluster headache study was a randomized, double-blind, placebo-controlled global trial evaluating the safety and efficacy of galcanezumab (300 mg once-monthly) administered subcutaneously compared with placebo in 106 patients with episodic cluster headache. Patients who participated in this trial had an average of 17.5 cluster headache attacks per week at baseline. The primary endpoint was the overall mean change from baseline in weekly cluster headache attack frequency across weeks one to three with galcanezumab compared with placebo. In this study, eight percent of patients treated with galcanezumab discontinued treatment during the study compared to 21 percent of patients treated with placebo. Discontinuations due to lack of efficacy occurred in two percent of patients treated with galcanezumab, compared to 14 percent of patients treated with placebo.

Alnylam Achieves Alignment with FDA on Accelerated Development Path for Lumasiran

May 14, 2018

Alnylam Pharmaceuticals announced that the company has reached alignment with the U.S. Food and Drug Administration (FDA) on a pivotal study design for lumasiran, an investigational RNAi therapeutic for the treatment of primary hyperoxaluria type 1 (PH1). The company and the FDA have aligned on a primary endpoint for the pivotal study based on reduction of urinary oxalate at six months, a biomarker directly linked to the pathophysiology of PH1 and known to be well correlated with disease progression. In addition, Alnylam and the FDA have aligned on a study size of approximately 25 patients with PH1. The ongoing Phase I/II Part B study is designed as a randomized, single-blind, placebo-controlled trial. Lumasiran demonstrated a mean maximal reduction in urinary oxalate of 66 percent with monthly dosing at 1 mg/kg in the unblinded Cohort 1 of the study (N=4), with all patients achieving urinary oxalate levels at or near the normal range. Moreover, lumasiran lowered urinary oxalate excretion in all patients below a threshold well documented to be associated with reduced progression to end-stage renal disease. In all patients, lumasiran was generally well tolerated and the only drug-related adverse event (AE) reported was a mild and transient injection site reaction.

New Phase IV Trial Data Showed that Epiduo Forte Decreased Acne Lesions

May 7, 2018

Galderma announced positive results from OSCAR, a Phase IV trial, multicenter, randomized, investigator-blinded, vehicle-controlled, intra-individual comparison study (right/left half-face). The purpose of OSCAR was to evaluate the efficacy of Epiduo Forte (adapalene and benzoyl peroxide) Gel, 0.3 percent/2.5 percent in the treatment of moderate-to-severe acne and to understand if, by decreasing active acne lesions, Epiduo Forte Gel could thereby decrease the risk of atrophic (depressed) acne scars. Results demonstrated Epiduo Forte Gel significantly decreased acne lesions, as measured over a period of 24 weeks vs. vehicle (P < .0001), with acne lesion reduction as early as week one. Subjects received 24 weeks of treatment with Epiduo Forte Gel or vehicle (half-face) and full-face skin care. At 24 weeks, based on satisfactory investigator-assessed efficacy and subject agreement, subjects could be treated with once-daily Epiduo Forte Gel on the full face for up to 24 additional weeks with two additional visits at weeks 36 and 48. According to a patient satisfaction survey, overall, 90.1 percent were satisfied to very satisfied with Epiduo Forte Gel vs. 59 percent with vehicle.

Alnylam Reports Results from the APOLLO Phase III Study

April 30, 2018

Alnylam Pharmaceuticals announced new results from the APOLLO Phase III study of patisiran, an investigational RNAi therapeutic for the treatment of hereditary ATTR (hATTR) amyloidosis. The APOLLO Phase III trial was a randomized, double-blind, placebo-controlled, global study designed to evaluate the efficacy and safety of patisiran in hATTR amyloidosis patients with polyneuropathy. The primary endpoint of the study was the change from baseline in modified Neurologic Impairment Score +7 (mNIS+7) relative to placebo at 18 months. The trial enrolled 225 hATTR amyloidosis patients from 19 countries with 39 genotypes who were randomized 2:1, patisiran:placebo, with patisiran administered at 0.3 mg/kg once every three weeks for 18 months. There were 13 deaths in the APOLLO study; none were considered related to study drug and the frequency of deaths was lower in the patisiran group (4.7 percent) as compared with placebo (7.8 percent). While treatment benefit is observed across all stages of disease, these results support the rationale for early treatment with patisiran to potentially halt or improve neuropathy progression or impairment, respectively.

Paratek Pharmaceuticals Presents Data for Skin Infections Trial
Paratek Pharmaceuticals announced that an analysis of microbiology data from OASIS-2, its second Phase III study of omadacycline in acute skin infections, found that once-daily monotherapy with oral omadacycline is effective in treating frequently isolated pathogens associated with skin infections. The OASIS-2 study was a randomized, double-blind, multi-center study that enrolled 735 adult subjects with moderate to severe ABSSSI at 33 centers in the U.S. Patients received either once-daily, oral omadacycline or twice-daily, oral linezolid for 7 to 14 days. To analyze clinical success per infection type in OASIS-2, the modified intent-to-treat (mITT) population included randomized subjects without a sole Gram-negative pathogen(s) at baseline (n=720). Infection type broke down as follows: 59 percent wound infection; 24 percent cellulitis/erysipelas and 18 percent major abscess. In the pivotal Phase III OASIS-2 study, omadacycline met the FDA-specified primary endpoint of statistical non-inferiority (NI) in the modified intent-to-treat (mITT) population (10 percent NI margin, 95 percent confidence interval) compared to linezolid at the early clinical response (ECR), 48 to 72 hours after the first dose of study drug.

Tarveda Therapeutics Doses First Patient in Phase I/IIa Study
Tarveda Therapeutics announced that it has dosed the first patient in a Phase I/IIa study evaluating PEN-866 in patients with advanced solid tumors. PEN-866 is a miniature drug conjugate that selectively binds to the intracellular target Heat Shock Protein 90 (HSP90) and is linked to SN-38, a known and potent anti-cancer payload. The multi-center, dose escalation and expansion study will assess safety and efficacy across a range of tumor types including those previously shown to be sensitive to topoisomerase 1 inhibitors. This includes but is not limited to small cell lung, pancreatic, triple negative breast, colon and ovarian cancers and sarcomas. The Phase IIa portion of the trial has now been initiated and enrollment has begun in patients with small cell lung cancer as well as GI-midgut and pancreatic neuroendocrine tumors that express SSTR2. PEN-866 is a miniature conjugate that comprises a small molecule, HSP90-targeting ligand linked to SN-38, the active metabolite of irinotecan. Checkmate Pharmaceuticals Announces Start of Phase Ib Trial
Checkmate Pharmaceuticals announced that it had initiated treatment with CMP-001 combined with atezolizumab (TECENTRIQ) in a Phase Ib clinical trial of patients with advanced non-small cell lung cancer (NSCLC) and disease progression on prior anti-PD-1/PD-L1 therapy. CMP-001 is designed to activate innate immunity to convert “uninflamed” tumors, which generally do not respond to anti-PD-1/L1 therapy, into “inflamed” tumors, which are responsive to PD-1 inhibition. The trial is designed as a multi-center, open label, two-part Phase 1b study of CMP-001 administered in combination with atezolizumab with and without low-level radiation therapy. Part one of the study will evaluate CMP-001 (5 mg dose) administered subcutaneously (SC) weekly for two weeks and then intratumorally (IT) weekly for three weeks, followed by either SC or IT injection every three weeks. In the second part of the trial, the combination of CMP-001 and atezolizumab therapy will be preceded by low-level radiation therapy to the target lesion.

Syros Announces New Preclinical Ovarian Cancer Study

April 23, 2018

Syros Pharmaceuticals announced new preclinical data showing that SY-1365, its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor currently in a Phase I trial in patients with advanced solid tumors, demonstrated potent anti-tumor activity in multiple models of heavily pretreated ovarian cancer. The ongoing Phase I trial of SY-1365 is a multi-center, open-label trial enrolling patients with advanced solid tumors. The primary objective of the trial is to assess the safety and tolerability of escalating doses of SY-1365, with the goal of establishing a maximum tolerated dose and a recommended Phase II dose and regimen. The dose-escalation phase is open and expected to enroll approximately 35 solid tumor patients for whom standard curative or palliative measures do not exist or are no longer effective. SY-136 showed induced cell death in numerous ovarian cancer cell lines and inhibited tumor growth in 10 of the 17 treatment-relapsed ovarian PDX models studied, including inducing complete regressions. Syros expects to open the expansion phase of the trial in mid-2018.

KEYTRUDA Monotherapy Met Primary Endpoint in Phase III Study

April 16, 2018

Merck announced that the pivotal Phase III KEYNOTE-042 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the first-line treatment of locally advanced or metastatic non-small cell lung cancer met its primary endpoint of overall survival. KEYNOTE-042 is an international, randomized, open-label Phase III study investigating KEYTRUDA monotherapy compared to standard-of-care platinum-based chemotherapy in patients with locally advanced or metastatic PD-L1 positive (TPS ≥1 percent) NSCLC. Patients had no EGFR or ALK genomic tumor aberrations and had not previously received systemic therapy for advanced disease. The primary endpoint is OS with TPS of ≥50 percent, ≥20 percent and ≥1 percent, which were assessed sequentially. The secondary endpoints are PFS and objective response rate (ORR). The study enrolled 1,274 patients randomized 1:1 to receive either KEYTRUDA (200 mg fixed dose every three weeks). The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported monotherapy studies involving patients with advanced NSCLC.

Allergan and Richter Announce Positive Topline Results for Bipolar I Depression Trial

April 9, 2018

Allergan and Gideon Richter announced positive topline results for RGH-MD-53, a Phase III study of cariprazine for the treatment of adults with major depressive episodes associated with bipolar I disorder (bipolar I depression). RGH-MD-53 and RGH-MD-54 were identical Phase III, randomized, double-blind, placebo-controlled, parallel-group, multicenter, fixed-dose clinical trials in adult patients with bipolar I depression. A total of 584 patients were randomized to evaluate the efficacy, safety and tolerability of cariprazine 0.75 mg, 1.5 mg and 3 mg compared to placebo in the treatment of outpatients with bipolar I depression. Patients underwent a no-drug screening period of approximately 7-14 days, followed by 8 weeks of double-blind treatment and a one-week, no investigational product safety follow-up period. Cariprazine was generally well tolerated in the trial. The overall incidence of patients who experienced adverse events was 51 percent for the cariprazine 1.5 and 3 mg dose groups, and 46 percent for the placebo group. The majority of adverse events were mild to moderate and led to discontinuation in approximately 5 percent of cariprazine-treated patients versus three percent of placebo-treated patients.

Ionis and Akcea Present New Data from ATTR Amyloidosis Program

April 2, 2018

Ionis Pharmaceuticals and its affiliate, Akcea Therapeutics, announced Phase III data showing that inotersen-treated patients with hereditary ATTR (hATTR) amyloidosis who were treated for up to 27 months in the NEURO-TTR and open-label extension (OLE) studies continued to demonstrate sustained benefit in measures of quality of life and neuropathy. The NEURO-TTR study was a Phase III randomized (2:1), double-blind, placebo-controlled, international study in 172 patients with polyneuropathy due to hATTR. The 15-month study measured the effects of inotersen on neurological dysfunction and on quality-of-life by measuring the change from baseline in the modified Neuropathy Impairment Score +7 (mNIS+7) and in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN) total score. The NEURO-TTR OLE is an ongoing study for patients who completed the NEURO-TTR study and is intended to evaluate the long-term efficacy and safety profile of inotersen. Significant benefit was observed in inotersen-treated patients with cardiac disease at baseline in both primary endpoints (Norfolk QoL-DN, p=0.036 and mNIS+7, p<0.001) and in the way they felt and functioned in the SF-36 Health Survey endpoint (p=0.025) at 15 months, compared to placebo.