Pipeline News and Updates
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Regulatory Update
The FDA accepted the NDA for sparsentan for the treatment of IgA nephropathy and set a PDUFA date for 11/7/2022 The FDA placed a hold on HIV trials using injectable lenacapavir, in December 2021, due to concerns regarding the compatibility of vials made of borosilicate glass with lenacapavir solution, which could potentially lead to the formation of sub-visible glass particles. The FDA allowed trials for injectable lenacapavir to resume in May 2022, after Gilead changed to an aluminosilicate glass vial that did not have compatibility problems with the drug. KalVista announced that generic name for KVD900 is sebetralstat Announced Research Updates BeiGene announced interim results from 32 patient enrolled in the 63 patient, open-label, Phase II, TRUCE-02 trial, where treatment with tislelizumab plus nab-paclitaxel resulted in a complete response rate of 62.5% in Chinese patients with high-risk non–muscle invasive bladder cancer (HR-NMIBC). Enanta announced that in a 14-day, 81 patient, Phase IIb trial, treatment with EDP-938 did not reduce the total symptom score compared to placebo in patients with mild, community-acquired RSV. Tricida announced it had stoped the 1,600 patient, Phase III, VALOR-CKD trial after 1,480 patients were enrolled and 237 had reached the primary endpoint of renal death, end-stage renal disease (ESRD), or a 40% or greater reduction in the estimated glomerular filtration rate (eGFR). No interim results for veverimer were announced for VALOR-CKD, but Tricida anticipates that final results will be available in 3Q22. VALOR-CKD is being stopped early because Tricida does not have enough funding to complete the trial as originally designed with completion forecast for 2024. Chinook Therapeutics announced interim results from a cohort of 20 patients with IgA nephropathy (IgAN) enrolled in the 12-week, 80 patient, Phase II AFFINITY trial, where treatment with atrasentan lowered the 24-hour urine protein creatinine ratio (UPCR) in 20 patients at six weeks by 38%. At 12 weeks, UPCR was reduced 49.9% in 18 patients and at 24 weeks, UPCR was lowered by 58.5% in 11 patients. Vera Therapeutics announced that in the 72-week, 16 patient, Phase IIa, JANUS trial, treatment with atacicept decreased serum anti-Gd-IgA1 levels by 28% with 25 mg and 39% with 75 mg in patients with IgA nephropathy (IgAN). Biohaven Pharmaceutical announced that in a 48-week, 213 patient, Phase III trial, treatment with troriluzole was no different that placebo in improving the modified functional Scale for the Assessment and Rating of Ataxia in patients with spinocerebellar ataxia. Idorsia announced that the Phase III, PRECISION trial, adding aprocitentan 12.5 mg and 25 mg to a fixed dose combination of amlodipine, valsartan and hydrochlorothiazide lowered blood pressure compared to adding placebo to the same combination in the 730 patient, 4-week, Part 1 of the study of patients with resistant hypertension. In the open-label, 32-week, Part 2 of PRECISION, blood pressure reduction was maintained with aprocitentan, amlodipine, valsartan and hydrochlorothiazide. All patients received the same combination of drugs and patients who switched from placebo achieved the same blood pressure reduction. In the 12-week, 614 patient, Part 3 of the trial aprocitentan was withdrawn for four weeks then patients were re-randomized to aprocitentan or placebo for 12 weeks. Patients who received aprocitentan had a reduction in blood pressure, while those on placebo had an increase. Published Research Updates In the 135 patient, Phase II, CITYSCAPE trial, treatment with tiragolumab plus atezolizumab improved the objective response rate (ORR) (31.3% vs 16.2%) and progression-free survival (PFS) (5.4 vs 3.6 months) compared to atezolizumab monotherapy in patients with PD-L1-positive metastatic non-small cell lung cancer. In the 12-month 477 patient, open-label, Phase III, EMERALD trial, treatment with elacestrant resulted in progression-free survival (PFS) at 12 months of 22.3% compared to 9.4% with investigator’s choice of fulvestrant, anastrozole, letrozole, or exemestane in patients with ER+/HER2- advanced breast cancer. In patients with an ESR1 mutation 12-month PFS was 26.8% with elacestrant compared to 8.2% with physician’s choice. In the 24-week, 171 patient, Phase IIb, ALPINE II 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. We just added 16 new drugs to the knowledgebase:
Regulatory Update
The FDA approved tirzepatide (Mounjaro, Lilly), on 5/13/2022, as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Tirzepatide was approved with a black box warning regarding an increased risk for thyroid c-cell tumors and is contraindicated in patients with medullary thyroid carcinoma Multiple Endocrine Neoplasia syndrome type 2. The FDA rejected bimekizumab for the treatment of moderate to severe plaque psoriasis due to inspection observations that need to be corrected. Biogen and Eisai completed a rolling submission for lecanemab for the treatment of early Alzheimer's disease. The FDA delayed the PDUFA dates for Amicus’ combination of cipaglucosidase alfa and miglustat by three months to allow more time to review new information. The new dates are 8/29/2022 for the miglustat NDA and 10/29/2022 for the cipaglucosidase alfa BLA. Green Valley discontinued a Phase III Alzheimer’s trial in May 2022 evaluating oligomannate due to insufficient funding to support the trial. The trial had enrolled 257 Alzheimer’s patients in North America, 118 in Europe and 64 in China. KemPharm bought Orphazyme in May 2022 and took over development of arimoclomol. KemPharm plans to refile an NDA for arimoclomol in 1Q23. Announced Research Updates Roche announced interim results from the 534 patient, Phase III, SKYSCRAPER-01 trial, where adding tiragolumab to atezolizumab did not improve PFS compared to atezolizumab alone in patients with PD-L1-high locally advanced or metastatic NSCLC. J&J announced that in the 295 patient, Phase Ib, TRIMM-2 trial, treatment with teclistamab plus daratumumab improved the overall response rate (ORR) compared to daratumumab alone in heavily pretreated patients with multiple myeloma. Gamida announced that in a long-term extension of a 125 patient, Phase III trial, patients who received an umbilical cord blood transplant (UCBT) and were treated with omidubicel did not achieve a statistically significant improvement in non-relapse mortality or survival one year after transplant compared to UCBT alone. BMS announced that in the 1,221 patient, open-label, Phase III, POETYK PSO-LTE trial, a two-year extension of the Phase III, POETYK PSO-1 and POETYK PSO-2 trial, efficacy at 60-weeks with deucravacitinib was maintained, with 77.7% of patients maintaining PASI-75 and 58.7% maintaining a Physicians Global Assessment score of 0 or 1 (clear/almost clear skin). Published Research Updates In the 36 patient cohort 1 of the 15-day, 72 patient, Phase II/III, CAPELLA trial, 88% (21/24) of patients that had oral lenacapavir added to a failing HIV-treatment regimen achieved at least a 0.5 log10 copies/mL reduction in viral load compared to 17% (2/12) that received the failing regimen only in patients with multidrug resistant HIV-1 infection. In the 178 patient, open-label, Phase III, ATTAIN trial, treatment with etirinotecan pegol did not improve overall survival compared to physician’s choice of eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel in patients with breast cancer and brain metastases. In a 12-week, 147 patient, Phase II trial, treatment with BI 1015550 resulted in a 5.7 ml increase in Forced Vital Capacity (FVC) compared to a 81.7 ml decrease with placebo in patients with idiopathic pulmonary fibrosis (IPF) who were not receiving an antifibrotic drug. Among IPF patients receiving an antifibrotic drug, there was a 2.7 ml increase in Forced Vital Capacity (FVC) compared to a 59.2 ml decrease with placebo. In a 52-week, 24 patient, Phase III trial, treatment with Oxalobacter formigenes did not decrease plasma oxalate levels compared to placebo in patients with PH. In a 24-week, 463 patient, Phase III SEED trial, treatment with dorzagliatin reduced HbA1c 1.07% compared to a 0.50% decrease with placebo, in Chinese patients with type 2 diabetes. In a 24-week, 767 patient, Phase III trial, adding dorzagliatin to metformin lowered HbA1c 1.02% compared to a 0.36% decrease with metformin monotherapy in Chinese patients with type 2 diabetes. In the 4-week, 115 patient, Phase III, URIROX-1 trial, treatment with reloxaliase reduced the 24-hour urinary oxalate excretion by 22.6% compared to a 9.7% decrease with placebo in patients with enteric hyperoxaluria. Regulatory Update
The FDA approved vonoprazan in combination with amoxicillin and clarithromycin (Voquenza Triple Pak, PhathomPharmaceuticals) and in combination with amoxicillin alone (Voquenza Dual Pak, Phathom Pharmaceuticals), on 5/3/2022, for the treatment of Helicobacter pylori infections. Announced Research Updates Astellas announced that in the 12-week, 501 patient, Phase III, SKYLIGHT 1 trials, patients treated with fezolinetant reduced the severity of moderate to severe VMS by 0.15 points at 4 weeks and 0.24 points at 12 weeks with 30 mg and 0.19 points at 4 weeks and 0.20 points at 12 weeks with 45 mg compared to placebo in patients with moderate to severe VMS. The frequency of moderate to severe VMS events per day versus placebo was reduced by 1.87 episodes at 4 weeks and 2.39 episodes at 12 weeks with 30 mg and 2.07 episodes at 4 weeks and 2.55 episodes at 12 weeks with 45 mg compared to placebo. Regulatory Update
The FDA approved mavacamten (Camzyos, Bristol Myers Squibb), on 4/29/2022, to improve functional capacity and symptoms in adults with symptomatic New York Heart Association (NYHA) class II to III obstructive hypertrophic cardiomyopathy.
The FDA rejected Hutchmed’s surufatinib for the treatment of advanced pancreatic and extrapancreatic neuroendocrine tumors and recommended a multiregional trial using a population that is similar to the U.S. population. The FDA rejected Junshi’s and Coherus’ toripalimab, in combination with gemcitabine and cisplatin, for the treatment of nasopharyngeal carcinoma and recommended a change in a manufacturing quality process. In December 2021, the FDA placed a hold on Pfizer’s fordadistrogene movaparvovec trials after the death of patient in a Phase Ib trial. The FDA allowed the trial to resume in April 2022. Sage and Biogen initiated a rolling NDA for zuranolone for the treatment of major depressive disorder. CHMP recommended approval of Amryt Pharma’s oleogel-S10 for the treatment of dystrophic and junctional epidermolysis bullosa. The FDA rejected oleogel-S10 in February 2022. Brickell sold marketing and development rights for sofpironium to Botanix Pharmaceuticals. Announced Research Updates Lilly announced that in the 72-week, 2,539 patient, Phase III, SURMOUNT-1 trial, adding tirzepatide to a reduced-calorie diet and increased physical activity resulted in a 16% weight loss with 5 mg, 21.4% with 10 mg and 22.5% with 15 mg compared to 2.4% reduction with placebo plus diet and increased activity in adults without type 2 diabetes who have obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease. At least a 5% reduction in body weight was achieved with tirzepatide in 89% with 5 mg and 96% with 10 mg and 15 mg compared to 28% with placebo. Novartis announced that in the 649 patient, Phase III, RATIONALE 306 trial, adding tislelizumab to chemotherapy improved overall survival compared to chemotherapy only in patients with advanced or metastatic esophageal squamous cell carcinoma. Novo announced that in the 26-week, 526 patent, Phase IIIa, ONWARDS 2 trial, once-weekly insulin icodec lowered HbA1c 0.93% compared to a 0.71% decrease with once-daily insulin degludec in patients with type 2 diabetes switching from daily insulin. Stealth announced that in the 48-week, 176 patient, Phase II, ReCLAIM-2 trial, treatment with elamipretide did not improve low luminance visual acuity nor geographic atrophy progression compared to placebo in patients with geographic atrophy secondary to dry age-related macular degeneration. Milestone announced that in the 169 patient. Phase III NODE-302 trial, a long term extension of the 431 patient, NODE-301 trial, 105 patients experienced 188 PSVT episodes with a conversion rate of 60.2% and a median time to conversion of 15.5 minutes with self-administered nasal etripam. In a 12-week, 302 patient, Phase III trial, treatment with CNTX-4975 did not reduce the Weekly Pain With Walking score in the index knee compared to placebo in patients with moderate-to-severe osteoarthritis knee pain. The results have not been announced, presented or published and are only available on clinicaltrials.gov Published Research Updates In the 52-week, 36 patient, Phase II/III, ASCEND trial, compared to placebo, treatment with olipudase resulted in an improvement in DLco (22% vs 3.0%), spleen volume (39% decrease vs 0.5% increase) and decrease in liver volume (28% vs 1.5%) in adult patients with acid sphingomyelinase deficiency (Niemann-Pick Disease). However, treatment with olipudase did not improve the Splenomegaly Related Score compared to placebo. In an interim analysis of a 1,153 patient, Phase IIb trial, vaccination with RSVpreF elicited an antibody response with transplacental transfer in pregnant women and their infants. In a ten patient, open-label, Phase II trial, treatment with clazakizumab for at least 2.5 years stabilized eGFR at 41.6 ml/min per 1.73 m(2) at 12 months and 38.1 ml/min per 1.73 m(2) at 24 months in kidney transplant patients with chronic active antibody-mediated rejection. |
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