Update for the week ended February 2, 2019

The FDA followed an advisory panel recommendation and rejected ALKS 5461 (samidorphan plus buprenorphine)and requested additional efficacy data. Alkermes drug had a PDUFA date of 1/31/2019.

In a 36-week open label extension of the AEGIS-CKD trial, patients originally treated with ferric maltol maintained hemoglobin levels and patients switched from placebo demonstrated a similar rise in hemoglobin. The FDA rejected ferric maltol during Shield’s first submission, but the company has resubmitted an NDA, which was accepted by the FDA in December 2018 and assigned a PDUFA date of 7/27/2019

Novo plans to submit an NDA for oral semaglutide at the end of 1Q19.

Roche discontinued the Phase III CREAD 1 and CREAD 2 trials after an interim analysis found that crenezumab was unlikely to improve Clinical Dementia Rating-Sum of Boxes (CDR-SB)scores compared to placebo in patients with prodromal or mild Alzheimer's disease. Roche has an ongoing Phase II trial evaluating crenezumab in cognitively healthy individuals in Colombia with an autosomal dominant mutation who are at risk to develop familial Alzheimer’s Disease.

Pfizer and Lilly announced that in a 24-week, 849 patient, Phase III trial, patients treated with tanezumab 5 mg had a greater decrease in the WOMAC pain subscale and WOMAC Physical Function subscale with an improvement in the patient’s Global Assessment of OA compared to placebo in patients with osteoarthritis. The 2.5 mg dose of tanezumab had a greater decrease in the WOMAC pain subscale and WOMAC Physical Function subscale, but no improvement in the patient’s Global Assessment of OA compared to placebo. In a 698 patient, Phase III trial, rapidly progressive osteoarthritis (RPOA) was observed in 1.3% of tanezumab and in an 849 patient, Phase III trial, RPOA was seen in 2.1% of patients. RPOA did not develop with any patient that received placebo in either trial. The ratio of Type 1 RPOA (joint space narrowing) to Type 2 RPOA (bone loss and joint destruction) is 2:1 in both trials.

Takeda announced that in the 15-month phase 1 portion of the 20,000 patient, Phase III, TIDES trial, two doses of Takeda’s dengue vaccine (TAK-003) demonstrated efficacy in preventing dengue fever caused by all four virus serotypes healthy in children and adolescents ages four to 16 years living in dengue-endemic areas. Part 2 of the TIDES trial will evaluate the vaccine at 21 months and include the secondary endpoints of efficacy by serotype, baseline serostatus and severity. Part 2 data is expected to be available at the end of 2019. Part 3 Orf the trial will evaluate efficacy and long-term safety for an additional three years. The BLA submission will be based on Part 1 and Part 2 data.

Two Phase III studies, ENGAGE and EMERGE, were initiated in 2015 to evaluate the safety and efficacy of aducanumab in slowing cognitive impairment and progression of Alzheimer's disease (AD). The trials should end in 2020. On 2/14/18, Biogen announced it would add an additional 255 patients to each trial to ensure a 90% chance of avoiding a false negative result. Biogen announced plans in early 2019 for a third Phase III trial that will evaluate aducanumab for the prevention or delay in the clinical onset of the disease.

In the 30-day, 632 patient, Phase III IMPACT 1 trial, cadazolid was non-inferior to vancomycin in reaching clinical cure (84% vs 85%) in patients with mild-to-moderate or severe C difficile infection. In the 30-day, 609 patient, Phase III IMPACT 2 trial, treatment with cadazolid did not reach non-inferiority to vancomycin in reaching clinical cure (81% vs 86%) in patients with mild-to-moderate or severe C difficile infection. Development of cadazolid was halted in 2018 after the failure of a Phase III trial.

Scynexis announced interim data from the 60 patient, Phase III, open-label, FURI trial where treatment with ibrexafungerp resulted in clinical benefits in 17 of 20 patients with difficult-to-treat mucocutaneous and invasive fungal infections that are refractory to or intolerant of currently available standards of care. Eleven patients achieved a complete or partial response and six patients a stable disease response. 

CTI withdrew the MAA for pacritinib when CHMP indicated another Phase III trial was needed.