New Drug Update for The Week Ending June 1

Regulatory Update

Vertex was developing elexacaftor (VX-445) and VX-659 in parallel trials for the treatment of Cystic fibrosis caused by the F508del genetic mutation. Both drugs were used in combination with tezacaftor/ivacaftor. In May 2019 Vertex announced it would cease development of VX-659 and move forward with a combination of tezacaftor/ivacaftor/elexacaftor. Elexacaftor was chosen because it demonstrated more favorable safety and tolerability profile and could be co-administered with hormonal contraceptives. Researchers estimate the combination of elexacaftor with tezacaftor/ivacaftor could treat the underlying cause of CF in 90% of cystic fibrosis patients. Ivacaftor is estimated to treat 40% of patients and the combination of tezacaftor/ivacaftor to treat half of CF patients. Vertex plans to submit an NDA for tezacaftor/ivacaftor/elexacaftor in 3Q19 and a MAA in 4Q19.

​Announced Research Updates

1. Cara announced that in the 12-week, 350 patient Phase III, KALM-1 trial, 51% of patients treated with difelikefalin had a 3-point or greater improvement in the weekly mean of the 24-hour Worst Itching Intensity Numeric Rating Scale (WI-NRS) compared to 28% of patients treated with placebo in hemodialysis patients with moderate-to-severe chronic kidney disease-associated pruritus.
2. Vertex announced that in a 24-week, 403 patient, Phase III trial, elexacaftor in combination with tezacaftor/ivacaftor demonstrated a mean improvement in ppFEV1 of 13.8% compared to a 0.2% loss with placebo in cystic fibrosis patients with one F508del mutation and one minimal function mutation. In a 4-week, 107 patient, Phase III trial of patients with two F508del mutations already receiving tezacaftor and ivacaftor, the addition of elexacaftor improved the ppFEV1 by 10.4% compared to a 0.4% with placebo.
3. Biogen announced 48-week interim data from 696 patients enrolled in the 2-year, Phase III, open label, EVOLVE-MS-1 trial, where treatment with diroximel fumarate resulted in a 72% reduction in the annualized relapse rate.
4. Celgene announced interim results from the long term, open label Phase III, DAYBREAK extension trial that enrolled 2,257 patients from the RADIANCE and SUNBEAM trials. After 18.5 months, treatment with ozanimod resulted in a reduction of the annualized relapse rate to 0.13 from the ARR at the end of the parent trials of 0.25 with interferon, 0.18 with ozanimod 0.5 mg and 0.15 with ozanimod 1 mg. 
5. Espiron announced that in a 12-week, 301 patient, Phase III trial, bempedoic acid and ezetimibe lowered LDL 36%, compared to 23% with ezetimibe, 17% with bempedoic acid and a 1.8% increase with placebo in patients on statins with high LDL despite treatment.
6. AbbVie announced that in a Phase II trial, veliparib added to capecitabine and radiotherapy did not lower the Neoadjuvant Rectal compared to just capecitabine and radiotherapy in patients with Stages 2 or 3 rectal cancer, rectal adenocarcinoma treated with mFOLFOX6.
7. Sanofi announced that in a 307 patient Phase III, open label, ICARIA-MM trial, isatuximab added to pomalidomide and low-dose dexamethasone resulted in progression free survival of 11.5 months compared to 6.5 months with pomalidomide and dexamethasone alone in patients with relapsed/refractory multiple myeloma.

 Published Research Updates

1. In the 63 patient, Phase Ib, HARMONY trial, buparlisib added to ruxolitinib did not decrease spleen volume compared to historical ruxolitinib monotherapy in patients with myelofibrosis.
2. The Phase III SPARTAN trial enrolled 2,156 patients with migraine, including those with a cardiovascular risk factors, but not cardiovascular disease. The percentage of patients that were pain free at two hours with lasmiditan were 28.6% with 50 mg, 31.4% with 100 mg, 38.8% with 200 mg compared to 21.3% with placebo. Most bothersome symptoms were relieved at two hours in 40.8% treated with lasmiditan 50 mg, 44.2% with 100 mg and 48.7% with 200 mg compared to 33.5% with placebo. The most common ADR were CNS-related (dizziness, somnolence, paraesthesia) Cardiovascular ADR occurred in 0.56% of lasmiditan patients compared to 0.1% of placebo patients.
3. In the 14-week, 598 patient, Phase III, SELECT-MONOTHERAPY trial, ACR20 was reached by 68% that switched to upadacitinib 15 mg and 71% that switched to 30 mg compared to 41% continuing on methotrexate in patients with active rheumatoid arthritis despite stable methotrexate.
4. In an 855 patient, Phase II trial, PF-06425090 Clostridium difficile vaccine demonstrated an immune response in healthy adults aged 65-85 years. Administering the vaccine at 0, 1, and 6 months produced stronger and more persistent immune responses at 12-months than a 1, 8, and 30-day regimen.
5. In a 50 patient, Phase II, open label trial, 38% of all patients treated with selumetinib had a sustained response in two groups of 25 patients with pediatric low-grade glioma.
6. In a 52-week, 67 patient, open label, post-marketing Japanese trial, type 2 diabetic patients that were receiving a GLP-1 receptor agonist had tofogliflozin added to GLP-1 to their regimen which resulted in a reduction of the HbA1c of 0.6%. The most common ADR were constipation, thirst, dehydration and pollakiuria.
7. In a 12-week, 151 patient, Phase II trial, ipatasertib added to paclitaxel did not improve the pathologic complete response compared to paclitaxel monotherapy in patients with early triple-negative breast cancer scheduled for surgery.