Pipeline News and Updates
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Regulatory Update
The FDA approved amivantamab (Rybrevant, Johnson & Johnson), on 5/21/2021, for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test. The EMA’s CHMP recommended approval of elivaldogene autotemcel for the treatment of Cerebral Adrenoleukodystrophy and odevixibat for the treatment of Progressive Familial Intrahepatic Cholestasis. The FDA accepted the NDA for maribavir for the treatment of resistance or refractory cytomegalovirus infection in transplant recipients and set a PDUFA date for 10/26/2021. Announced Research Updates ImmunoGen announced that in a 60 patient cohort enrolled in the Phase Ib FORWARD II trial, treatment with the combination of mirvetuximab and bevacizumab resulted in an ORR of 50% overall and 64% in patients with high FR-Alpha expression in patients with FR-alpha, platinum-resistant ovarian cancer. Lilly announced that in the 52-week, 2,002 patient, Phase III, SURPASS-4 trial, treatment with tirzepatide reduced HbA1c by 2.24% to 2.58% and body weight by 7.1 Kg to 11.7 kg compared to an HbA1c decrease of 1.44% and 1.9 Kg gain with insulin glargine in inadequately controlled type 2 diabetics with increased cardiovascular risk. BeiGene announced that an interim analysis of the 263 patient, Chinese Phase III, RATIONALE 309 trial, suggested that treatment with tislelizumab plus gemcitabine and cisplatin improved progression free survival compared to gemcitabine and cisplatin alone in patients with recurrent or metastatic nasopharyngeal cancer. Ferring announced that in the 8-week, 267 patient, Phase III, PUNCH CD3 trial, 69.6% of patients treated with a single dose of RBX2660 developed C. difficile diarrhea compared to 41.9% who received placebo in adults who had at least one recurrence after a primary episode of C. difficile infection. Aveo announced that in a 60 patient, Phase II trial, treatment with ficlatuzumab plus cetuximab resulted in progression free survival of 3.6 months compared to 1.8 months with ficlatuzumab in patients with metastatic HNSCC who relapsed or were refractory to prior immunotherapy, chemotherapy, and cetuximab. Seres announced that in 24-week, 182 Phase III, ECOSPOR III trial, 21.3% of patients treated with SER-109 developed a C. difficile infection compared to 47.3% with placebo in patients with recurrent C. difficile infection. NGM announced that in the 24-week, 171 patient, Phase IIb, ALPINE 2/3 trial, patients treated with aldafermin did not demonstrate an improvement in fibrosis by at least one stage with no worsening of steatohepatitis compared to placebo in patients with biopsy-confirmed NASH with F2-F3 liver fibrosis. Takeda announced that in a follow-up of the TIDES trial, the effectiveness of the TAK-003 Dengue vaccine was found to be 62% and hospitalizations were avoided in 83.6% of patients three years after the second vaccination. Published Research Updates In a 125 patient, Phase II trial, 46% of patients treated with veliparib plus radiotherapy, followed by adjuvant veliparib and temozolomide achieved progression-free survival at 6 months compared to 31% treated with temozolomide and radiotherapy, followed by adjuvant temozolomide in patients with glioblastoma with unmethylated O 6-methylguanine-DNA methyltransferase (MGMT) promoter status. There was no difference in overall survival (12.7 vs 12.8 months). In a 48-week, 259 patient, Phase II trial, 32% to 42% of patients treated with oteseconazole achieved clinical and mycological cure compared to none with placebo in patients with moderate-to-severe distal and lateral subungual onychomycosis of the toenail. In a 24-week, 264 patient, Phase II trial, CRP was lowered more that placebo by 66.2% with ziltivekimab 7.5 mg, 77.7% with 15 mg and 87.8% with 30 mg at 12-weeks, with the results remaining stable to 24-weeks, in patients with moderate to severe chronic kidney disease, and CRP of at least 2 mg/L. In the U.S./Canadian cohort of the 12-month, 1,864 patient, Phase III, open label, E4 Freedom trial, treatment with estetrol 15 mg in combination with drospirenone 3 mg result in a Pearl Index (PI) of 2.65, method failure PI of 1.43 and 13-cycle life-table pregnancy rate of 2.1% among 1,674 women 16-35. Efficacy data was not reported in the 190 women who were 36 to 50. In an 8-week, 162 patient, Phase IIa trial, cannabidivarin was no different from placebo in decreasing the frequency of focal seizures (40.5% reduction vs 37.7% reduction) in patients with inadequately controlled focal seizures. In the 12-week, 662 patient Phase III, ZEAL 1 trial, treatment with fevipiprant did not result in a significant improvement in FEV1 compared to placebo (112 ml vs 71 ml) in patients with uncontrolled asthma. In the 12-week, 685 patient Phase III, ZEAL 2 trial, treatment with fevipiprant did not result in a significant improvement in FEV1 compared to placebo (126 ml vs 157 ml) in patients with uncontrolled asthma. In a 120 patient, Chinese, Phase II study treatment with anlotinib resulted in a PFS of 4.1 months compared to 0.7 months with placebo in patients with small-cell lung cancer. Regulatory Update
The FDA approved pegcetacoplan (Empaveli, Apellis Pharmaceuticals), on 5/14/2021, for the treatment of paroxysmal nocturnal hemoglobinuria in both treatment naïve patients and patients switching from eculizumab or ravulizumab. Pegcetacoplan was approved with a Black Box warning regarding the increased risk of meningococcal and other serious infections caused by encapsulated bacteria that may become rapidly life threatening or fatal if not recognized and treated early. A Risk Evaluation and Mitigation Strategy (REMS) program requires prescribers to counsel patients on the risk of serious infection, provide patients with the REMS educational materials, and ensure patients are vaccinated against encapsulated bacteria. The FDA approved an extended-release, locally administered solution of bupivacaine and meloxicam (Zynrelef, Heron Therapeutics), on 5/13/2021, for postsurgical analgesia after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty. The FDA accepted the NDA for levoketoconazole, for the treatment of endogenous Cushing’s syndrome and set a PDUFA date for 1/1/2022. The FDA granted losmapimod Fast Track status for the treatment of facioscapulohumeral muscular dystrophy. Announced Research Updates Biogen announced that in the 12-month, 50 patient, Phase II/III XIRIUS trial, treatment with cotoretigene toliparvovec did not improve Macular Integrity Assessment (MAIA) Microperimetry compared to an untreated group of male patients with X-linked retinitis pigmentosa. Published Research Updates In a 196 patient, Japanese study, elobixibat was similar to sodium picosulfate when either drug was added to 1 L of polyethylene glycol formulation containing ascorbic acid as a bowell cleaning preparation for colonoscopy as evidenced by similar Boston Bowel Preparation Scale scores (8.3 vs 8.3). In the 392 patient, Phase III AHELP trial, treatment with apatinib resulted in overall survival of 8.7 months compared to 6.8 months with placebo in Chinese patients with pretreated advanced hepatocellular carcinoma. In the 52-week, 1,061 patient, Phase III NAVIGATOR trial, the annualized asthma exacerbation rate with tezepelumab was 0.93 compared to 2.1 with placebo in patients 12 to 80 with severe uncontrolled asthma. In the 16-week, 440 patient, Phase III, BREEZE-AD5 trial, 30% of patients treated with baricitinib 2 mg achieved EASI-75 compared to 8% with placebo in patients with moderate to severe atopic dermatitis. Improvement with a 1 mg dose of baricitinib did not reach significance. In a draft review of JAK inhibits for the treatment of atopic dermatitis, ICER estimated the annual cost of abrocitinib at $37,500 to be cost-effective at $150,000 per QALY. ICER found insufficient evidence to compare abrocitinib to dupilumab. ICER also found that abrocitinib may improve severity, itch and sleep compared to topical therapies. The evidence is considered insufficient to compare abrocitinib, upadacitinib, baricitinib and tralokinumab. In a draft review of JAK inhibits for the treatment of atopic dermatitis, ICER estimated the annual cost of tralokinumab at $31,500 to be cost-effective at $150,000 per QALY. Based on available evidence ICER found the evidence for tralokinumab to be comparable or inferior to dupilumab. ICER also found that tralokinumab may improve severity, itch and sleep compared to topical therapies. Based on indirect evidence, abrocitinib and upadacitinib appear to have more favorable outcomes than baricitinib or tralokinumab. Regulatory Update
Hutchmed completed a rolling NDA for surufatinib as a treatment of pancreatic and extra-pancreatic neuroendocrine tumors. An FDA review of avacopan questioned whether data supported efficacy, because it was difficult to determine if the beneficial effect was caused by avacopan or rituximab/cyclophosphamide. The FDA also felt there was not enough historical data on the effects of prednisone to justify a non-inferiority trial design. The FDA’s Arthritis Advisory Committee voted 10 to 8 to recommend approval of ChemoCentryx’s avacopan to treat anti-neutrophil cytoplasmic autoantibody (ANCA)-vasculitis. The committee was split 9 to 9 on whether efficacy data supported approval and 10 to 8 on whether the safety profile supported approval. Amgen submitted a BLA for tezepelumab for the treatment of severe asthma. Announced Research Updates Bayer announced that in the 53-month, 7,437 patient, Phase III, FIGARO-DKD trial, treatment with finerenone reduced the composite endpoint of time to first occurrence of cardiovascular death or non-fatal CV events (myocardial infarction, stroke, or hospitalization for heart failure) compared to placebo in type 2 diabetics with chronic kidney disease. AstraZeneca announced preliminary results from the 1,013 patient, Phase III, open-label, POSEIDON trial, PFS and OS were both improved with durvalumab, tremelimumab and platinum-based chemotherapy, while durvalumab plus platinum-based chemotherapy only improved PFS compared to platinum-based chemotherapy alone as first line treatment in patients with metastatic non-small cell lung cancer without epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions. Orphazyme announced that in the 76-week, 245 patient, Phase III, ORARIALS-01 trial, treatment with arimoclomol did not improve the combined assessment of function and survival (CAFS) score compared to placebo in patients with amyotrophic lateral sclerosis. Published Research Updates In the 318 patient, Phase III, ALLEVIATE trial, a greater percentage of patients treated with reproxalap 0.25% and 0.5% ophthalmic solutions reduced the ocular itch score within 10 to 60 minutes after allergen challenge compared to placebo in patients with seasonal allergic conjunctivitis. In a 12-week, 27 patient, Phase II, open-label trial, 52% of patients treated with rilzabrutinib Achieved Control of Disease Activity (no new lesions, existing lesions healing) at 4-weeks in patients with pemphigus foliaceus. In a draft evidence report for aducanumab, ICER found the evidence to be insufficient to support efficacy and estimates a cost-effective range of $2,500 to $8,300 per year. In the 378 patient, extension of the Phase II, FORWARD trial, patients treated with sprifermin maintained the 0.05 mm increase in femorotibial joint cartilage thickness compared to placebo at five years. Overall, there was no improvement in WOMAC score compared to placebo, however, no patient in the 100 mcg group required knee replacement. In a subgroup of 161 patients at risk for progression, a decrease in the WOMAC score was maintained through year five. Regulatory Update
The FDA accepted the NDA for bardoxolone methyl for the treatment of chronic kidney disease caused by Alport syndrome and set a PDUFA date for 2/25/2022. In April 2021, Lilly discontinued development of mirikizumab for the treatment of psoriasis. Lilly has ongoing trials evaluating mirikizumab in the treatment of ulcerative colitis and Crohn's disease. Beginning in mid-July, Biogen will allow access through a compassionate use program for tofersen to treat rapidly progressing ALS patients with SOD1 mutations. In the fall of 2021, if tofersen is found to be safe and effective in a Phase III trial, an Early Access Program will be initiated for a broader range of ALS patients with SOD1 mutations. Enzyvant resubmitted a BLA for RVT-802 for the treatment of pediatric patients with congenital athymia. The FDA delayed review of pegunigalsidase alfa until a site inspection could be completed at Protalix's manufacturing facility in Carmiel, Israel. The FDA rejected the NDA for tralokinumab and requested additional information on a device used in the delivery of the drug. The EMA’s CHMP recommended approval of the MAA for tralokinumab for the treatment of moderate-to-severe atopic dermatitis. The FDA has extended the PDUFA date for BioMarin's vosoritide by three months to allow additional time to review recently submitted results from a two-year Phase III extension study. Announced Research Updates Aldeyra announced that in the 210 minute 95 patient, Phase III, INVIGORATE trial, treatment with reproxalap 0.25% ophthalmic solution reduced the subject-reported ocular itching score compared to placebo in patients with seasonal allergic conjunctivitis. Revance announced that in an 84-week, analysis of 568 patients from the Phase III, SAKURA 3 trial, four-weeks after the first injection of daxibotulinumtoxinA, up to 57.9% of patients perceived no static Glabellar lines (GL). After a second injection 68.7% reported no GL and 71.5% after the third treatment in patients with mild and moderate static Glabellar lines. Similar improvements were observed by investigators. Patients with severe static GL also achieved no static GL with a third cycle of daxibotulinumtoxinA. Pharnext announced interim results after 54-months from a long-term extension of the Phase III study PLEO-CMT trial. In the PLEO-CMT-FU extension trial, treatment with PXT3003 continued to demonstrate an improvement in the ONLS compared to placebo in patients with mild to moderate Charcot-Marie-Tooth Type 1A Disease. Brickell announced that 190 patients completed the 52-week, 300 patient, Phase III ARGYLE trial, where treatment with sofpironium bromide improved the proprietary patient-reported Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) scale by one-point in 86.1% of patients that received a 5% gel and 85.8% with the 15% gel in patients with primary axillary hyperhidrosis. A two-point improvement in the HDSM-Ax score was achieved by 69.4% of 5% patients and 61.9% of 15% patients. Mostly mild or moderate adverse events were experienced by 22.5% of patients treated with sofpironium bromide gel 5% and 50.8% with 15%. Most adverse events were transient, so treatment discontinuations decreased over time. AB Science announced that in a 580 patient, Phase IIb/III trial, treatment with masitinib plus docetaxel and prednisone improved progression-free survival compared to docetaxel and prednisone alone in patients with metastatic castration-resistant prostate cancer. Published Research Updates In the 36-week, 1,751 patient, Phase III, PRO2TECT Correction trial, vadadustat was non-inferior to darbepoetin in the change in hemoglobin, 1.43 vs 1.38 for a 0.05 g/dL difference, in CKD patients with anemia not on dialysis, who had not received previous ESA treatment. In the 36-week, 1,725 patient, Phase III, PRO2TECT Conversion trial, vadadustat was non-inferior to darbepoetin in the change in hemoglobin, 0.41 vs 0.42 for a 0.01 g/dL difference, in CKD patients with anemia not on dialysis, treated with an ESA. The incidence of MACE (composite endpoint of all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke) with vadadustat compared to darbepoetin in the two PRO2TECT trials involving 3,471 CKD patients with anemia not on dialysis, found that 22% of vadadustat patients experienced a MACE event compared to 19.9% with darbepoetin for a hazard ratio of 1.17. In the 36-week, 369 patient, Phase III, INNO2VATE Correction/Conversion trial, vadadustat was non-inferior to darbepoetin in the change in hemoglobin, 1.26 vs 1.58 for a 0.31 g/dL difference, in patients receiving chronic dialysis for end-stage renal disease. In the 36-week, 3,554 patient, Phase III, INNO2VATE Conversion trial, vadadustat was non-inferior to darbepoetin in the change in hemoglobin, 0.19 vs 0.36 for a 0.17 g/dL difference, in patients receiving chronic dialysis for end-stage renal disease. The incidence of MACE (composite endpoint of all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke) in the two INNO2VATE trials involving 3,902 patients with anemia and dialysis-dependent chronic kidney disease, was 18.2% with vadadustat, which was non-inferior to 19.3% with darbepoetin for a hazard ratio of 0.96. In the 260 patient, Phase II, INTELLANCE-2, open label trial treatment with depatuxizumab and temozolomide did not improve the overall survival rate compared totemozolomide alone in patients with EGFR-amplified glioblastoma. In a 4-week, 416 patient, Phase IIb, dose ranging trial, ensifentrine plus tiotropium increased FEV1 compared to tiotropium alone (ensifentrine dose-dependent increase of 77.5 mL to 124.2 mL) in patients with chronic obstructive pulmonary disease. |
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