Pipeline News and Updates
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Regulatory Update
The FDA accepted the NDA for sotorasib for the treatment of patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer, following at least one prior systemic therapy. The PDUFA date for sotorasib’s NDA is 8/16/2021. The FDA advised Brainstorm in February 2021 that current evidence was not strong enough to support a BLA for NurOwn. Announced Research Updates The FDA has placed a partial hold on an open-label extension of Cortexyme’s 54-week, 643 patient, Phase II/III GAIN trial. The trial is evaluating the effect of atuzaginstat on the MMSE score in 570 patients with mild to moderate Alzheimer's disease. The hold was ordered due to hepatic adverse events. No new patients will be enrolled in the GAIN trial and atuzaginstat will be discontinued in the trial extension. Current GAIN patients will complete atuzaginstat treatment with results expected by the end of 2021. Lilly announced that in the 52-week, 1,444 patient, Phase III SURPASS-3 trial, treatment with tirzepatide reduced HbA1c by 1.93% to 2.37% and body weight by 7.5 Kg to 12.9 kg compared to an HbA1c decrease of 1.34% and 2.3 Kg gain with insulin degludec in insulin-naive patients with type 2 diabetes and inadequate glycemic control on stable doses of metformin with or without an SGLT-2 inhibitor. Lilly announced that in the 40-week, 475 patient, Phase III SURPASS-5 trial, treatment with tirzepatide reduced HbA1C by 2.23% to 2.59% and body weight by 6.2 Kg to 10.9 kg compared to an HbA1c decrease of 0.93% and 1.7 Kg gain with placebo in insulin-naive patients with type 2 diabetes. Zymeworks announced that in a 280 patient, Phase II, open-label trial, treatment with zanidatamab alone resulted in an overall response rate (ORR) of 33% and 54% when used in combination with paclitaxel or capecitabine in patients with HER2-expressing gastroesophageal adenocarcinoma. Immunic announced that in a 24-week, 30 patient, open-label, Phase II trial, only 18 patients were enrolled in the trial due to COVID19 restrictions. Of the 18 patients, only 11 completed treatment and had data available. Three of 11 patients treated with vidofludimus achieved a reduction of ALP of at least 25, while their AST increase at week 24 was no more than 33%, in patients with primary sclerosing cholangitis. Dermavant announced interim results from 520 patients who completed either the PSOARING 1 or PSOARING 2, Phase III, tapinarof trials and were enrolled in the 40-week open-label, long-term extension, Phase III, PSOARING 3 trial. 57.3% of the study population achieved a PGA score of clear or almost clear in patients with plaque psoriasis, treated with tapinarof, who started the trial with a PGA score of two or more. Published Research Updates In a 165 Chinese patient, Phase II study anlotinib demonstrated an average PFS of 3.02 months compared to 1.41 months with placebo in patients with recurrent or metastatic esophageal squamous cell carcinoma. In a 24-week, 695 patient, Phase IIb trial, treatment with lorecivivint 0.07 mg decreased the Pain Numeric Rating Scale (NRS) 0.7 points and 0.23 mg decreased the score by 0.82 points more than placebo in patients with knee osteoarthritis. Lorecivivint 0.23 mg also improved both the WOMAC pain (7.36 point decrease) and function (7.99 point decrease) scores. Lorecivivint 0.03 mg and 0.15 mg did not improve the Pain NRS or WOMAC scores compared to placebo. In the 52-week, 331 patient, Phase III, ADVOCATE trial, 72.3% of patients treated with avacopan achieved remission (BVAS score of zero and no glucocorticoid treatment for anti-neutrophil cytoplasmic antibody-associated vasculitis for at least the preceding four weeks) at 26 weeks compared to 70.1% with corticosteroids in patients with antineutrophil cytoplasmic antibody–associated vasculitis. 65.7% of avacopan patients remained in remission at 52 weeks compared to 54.9% with glucocorticoids. A pooled analysis of 925 patients that participated in the MUSE, TULIP-1 and TULIP-2 trials found the most common adverse events with anifrolumab compared to placebo were infections (69.7% vs 55.4%). In a 24-week, 40 patient, open label, trial, treatment with tofogliflozin reduced the MRI-proton density fat fraction 4.12% compared to a 7.54% decrease with pioglitazone in Japanese patients with non-alcoholic fatty liver disease and type 2 diabetes. In the 444 patient, Phase III, open-label, TAHOE trial, treatment with rovalpituzumab tesirine resulted in an overall survival of 6.3 months compared to 8.6 months with topotecan in patients with DLL3-high advanced or metastatic SCLC. AbbVie stopped enrollment in the TAHOE trial early, after an interim review by the independent data monitoring committee found shorter overall survival with rovalpituzumab tesirine as second line treatment. Astellas announced data after 12 weeks from 1,028 patients enrolled in the Phase III SKYLIGHT 1 and SKYLIGHT 2 trials, where treatment with fezolinetant reduced the frequency and severity of vasomotor symptoms (VMS) compared to placebo in patients with moderate to severe VMS. In a 52-week, 378 patient, Phase II trial, treatment with tilavonemab did not improve the Progressive Supranuclear Palsy Rating Scale score compared to placebo in patients with progressive supranuclear palsy. The trial was discontinued after a futility analysis failed to find a benefit with tilavonemab. In the 456 patient, Phase II ICON6 trial, treatment and maintenance with cediranib improved progression-free survival compared to placebo in patients with relapsed platinum-sensitive ovarian cancer. The ICON6 trial was redesigned while the trial was going on, so overall survival was underpowered and did not show a benefit compared to placebo. JAMA published an interesting article about the increased cost with new oncology drugs and the impact based on their use.
The article notes that “The growth of cancer drug spending in the US has outpaced spending in nearly all other sectors, and an increasing proportion of the drug development pipeline is devoted to oncology. This 2018 study notes that in order to maintain the 2018 level of drug spending less than 20% of eligible patients could be treated. Oncology new drug candidates comprise 17.5% of our current knowledgebase of late stage investigational drugs (160/913). Prescribe Right’s list of recent FDA oncology drug approvals, begins with avapritinib (January 9, 2020) and ends with tepotinib (February 23, 2021) totaling twenty-two out of a total of fifty-one recent approvals. All of the new approvals during 2020 were available within thirty days of approval. We wonder how many have made it into formularies. Recent surveys indicate that P&T Committees sometimes wait for up to six months of post-launch data to study prior to making a formulary decision. Click here to review our complete our list of recent approvals. Pricing is included for all 2020 approvals. Regulatory Update
The FDA approved trilaciclib (Cosela, G1 Therapeutics), on 2/12/2021, to reduce the frequency of chemotherapy-induced bone marrow suppression in extensive-stage small cell lung cancer patients being treated with a platinum/etoposide containing regimen or a topotecan containing regimen. The FDA granted Breakthrough Therapy Designation to asciminib for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia. Announced Research Updates Galapagos and Gilead announced that an analysis of interim data from patients enrolled in the 52-week, 1,500 patient, Phase III, ISABELA 1 & 2, IPF trials, by the Independent Data Monitoring Committee, resulted in a recommendation to stop the trials, because the ziritaxestat benefit-risk profile did not support continuation. Sumitomo Dainippon announced that in the 1,250 patient, open-label, Phase III, CanStem303C trial, adding napabucasin to FOLFIRI with or without bevacizumab did not improve overall survival (OS) compared to the combination without napabucasin in patients with metastatic colorectal cancer. There also was not an improvement in OS in a subset of patients with phosphorylated signal transducer and activator of transcription 3 (pSTAT3) biomarker mutations. Mesoblast announced that in a 24-month, 404 patient, Phase III trial, the reduction in pain using a Visual Analog Score (VAS) at 12-months and 24-months was greater with rexlemestrocel-L alone and rexlemestrocel-L plus hyaluronic acid than placebo in patients with chronic low back (LBP) pain due to degenerative disc disease refractory to conventional treatments. The decrease was about half with rexlemestrocel-L alone compared to the combination. In a subgroup of patients receiving opioids for LBP, rexlemestrocel-L plus hyaluronic acid reduced opioid use, while patients in the placebo group increased opioid use. Takeda announced that in the eight-week, 352 patient, Phase III, SOLSTICE trial, 55.7% of patients treated with maribavir achieved confirmed CMV viremia clearance compared to 23.9% with investigator-assigned treatment (ganciclovir, valganciclovir, foscarnet, or cidofovir) in transplant patients with refractory/resistant CMV infection. Amicus announced that in the 52-week, 123 patient Phase III, PROPEL trial, patients treated with cipaglucosidase alfa/miglustat had a non-significant improvement in their six-minute walk-test distance (6MWD) by 21 meters compared to a 7 meter improvement with alglucosidase alfa (p=0.072) in patients with late-onset Pompe disease. Patients treated with cipaglucosidase alfa/miglustat had a significant slowed rate of FVC decline compared to alglucosidase alfa (0.9% decline vs 4% decline). Merck announced interim results from 41 patients enrolled in a 118 patient, Phase II, open-label trial, treatment with belzutifan plus cabozantinib resulted in a 22% ORR in patients with RCC. Published Research Updates In a 52-week, 217 patient, Phase III trial, oral daprodustat was non-inferior to darbepoetin in maintaining hemoglobin levels (12 g/dl vs 11.9 g/dl) during weeks 40 to 52 in non-dialysis dependent Japanese patients with anemia associated with chronic kidney disease. In a 128 patient, Phase II trial, treatment with spartalizumab resulted in a 7.4% overall response rate in patients with neuroendocrine tumors and 4.8% in patients with gastroenteropancreatic neuroendocrine carcinomas. In the 267 patient, open-label, Phase III, PHOEBE trial, treatment with pyrotinib plus capecitabine resulted in progression-free survival of 12.5 months compared to 6.8 months with pyrotinib plus lapatinib in Chinese patients with HER2-positive relapsed or metastatic breast cancer previously treated with taxanes and trastuzumab. In a 52-week, 2,781 patient, Phase III trial, treatment with roxadustat improved hemoglobin 1.75 g/dl compared to a 0.4 g/dl increase with placebo in non-dialysis-dependent CKD patients with anemia. In a 432 patient, Phase III trial, adding andecaliximab to mFOLFOX6 did not improve overall survival compared to mFOLFOX6 alone (12.5 vs 11.8 months) in patients with untreated human epidermal growth factor receptor 2-negative gastric or gastroesophageal junction adenocarcinoma. In a 608 patient Phase III, open label trial, where treatment with enfortumab vedotin resulted in overall survival of 12.88 months compared to 8.97 months with investigator-chosen chemotherapy (standard docetaxel, paclitaxel, or vinflunine), in patients with locally advanced or metastatic urothelial cancer who progressed after receiving platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. In a 24-week, 213 patient, Phase III, TIMES 1 trial, imeglimin lowered HbA1c 0.87% more than placebo in Japanese patients with type 2 diabetes. In a 147 patient, open-label, Phase II trial, treatment with sunitinib, crizotinib, or savolitinib did not improve progression-free survival compared to cabozantinib in patients with metastatic papillary renal cell carcinoma. In a 200 patient, Phase II trial, 66% of patients treated with Lu-PSMA-617 achieved a 50% or greater reduction in their PSA response rate (PSA50-RR) compared to 37% treated with cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC), eligible for cabazitaxel treatment. Regulatory Update
The FDA approved tepotinib (Tepmetko, EMD Serono) on 2/3/2021, for the treatment of metastatic non-small cell lung cancer harboring METex14 skipping alterations. Tepotinib will compete with capmatinib, which is also approved for the treatment of NSCLC harboring METex14 skipping alterations. Tepotinib is dosed 450 mg once daily. Capmatinib is dosed 400 mg twice a day. WAC for a month’s supply of capmatinib is $20,290. Both drugs have been evaluated as a treatment for NSCLC harboring METex14 skipping alterations. In the 152 patient, VISION trial, treatment with tepotinib resulted in an overall response rate of 46%. In the 364 patient GEOMETRY mono-1 trial, treatment with capmatinib resulted in an overall response rate of 41% in the pre-treated group and 68% in the treatment-naive group. The FDA approved lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb), on 2/5/2021, for the treatment of relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. Lisocabtagene maraleucel was approved with a Black Warning regarding Cytokine Release Syndrome and Neurologic Toxicities. Lisocabtagene maraleucel is the third approved CAR-T cell therapy. Marketed CAR-T cell therapies include tisagenlecleucel (Kymriah, Novartis), approved in 2017 for the treatment of acute lymphoblastic leukemia and in 2018 for large B-cell lymphoma. The other CAR-T cell therapy is Gilead’s axicabtagene ciloleucel (Yescarta), which is approved to treat relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and DLBCL arising from follicular lymphoma. Both drugs have the same Black Box Warning as lisocabtagene maraleucel. Tisagenlecleucel and axicabtagene ciloleucel have a WAC of $373,000 per dose, while BMS has set WAC for lisocabtagene maraleucel at $410,300 per dose. The FDA approved umbralisib (Ukoniq, TG Therapeutics), on 2/5/2021, for the treatment of relapsed or refractory marginal zone lymphoma or refractory follicular lymphoma. Announced Research Updates BMS announced that in the 16-week, 1,020 patient, Phase III, POETYK PSO-2 trial, more patients treated with deucravacitinib achieved PASI 75 and a Physician's Global Assessment (sPGA) score of 0 to 1 compared to apremilast or placebo in patients with moderate to severe psoriasis. Mustang Bio plans to initiate a 10 patient, Phase III trial in 2021 to evaluate MB-107 in the treatment of XSCID. Results of the trail will be combined with 15 patents treated with MB-107 in earlier studies. The combined results will be compared to a historical group of XSCID patients treated with hematopoietic stem cell transplantation. PTC announced that in a 40-week, 20 patient, Phase II trial, treatment with ataluren resulted in an insignificant increase of dystrophin levels in patients with Duchenne muscular dystrophy. AZ announced that in the 823 patient, Phase III, open-label, KESTREL trial, neither durvalumab monotherapy nor durvalumab plus tremelimumab improved overall survival compared to cetuximab, fluorouracil, cisplatin or carboplatin in patients with recurrent or metastatic head and neck squamous cell cancer. Published Research Updates A long-term extension of 1,820 patients who completed the SIRROUND-D and SIRROUND-T Phase III trials, found that a reduction in rheumatoid arthritis symptoms and control of disease with sirukumab were maintained. No new safety conversion were found. The most common adverse events were infections. In an extension of the Phase II DARWIN 1 & 2 trials, 739 patients continued for a total of four or more years in the Phase II, DARWIN 3, open label trial. The ACR20/50/70 responses were 89.3%/69.6%/49.1% with filgotinib plus MTX and 91.8%/69.4%/44.4% with filgotinib alone. In a 12-week, 300 patient, Phase IIb trial, reproxalap reduced signs and symptoms of dry eye disease compared to placebo in patients with dry eye disease. In a 120 patient, Phase II trial, treatment with pevonedistat and azacitidine resulted in overall survival of 21.8 months compared to 19 months with azacitidine alone in patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) or low-blast acute myeloid leukemia (LB-AML) who had not previously received a hypomethylating agent. In a 16-week, 3,021 patient, Phase III trial, treatment with tanezumab 5mg administered subcutaneously every 8 weeks significantly improved the WOMAC Pain and Physical Function score, but not in the Patient's Global Assessment of Osteoarthritis score compared to naproxen, celecoxib or diclofenac in patients with moderate-to-severe osteoarthritis of the hip or knee. Tanezumab 2.5mg did not differ from placebo in either of the primary endpoints. In the 16-week, 567 patient, Phase III, BE VIVID trial, 85% of patients treated with bimekizumab achieved a 90% Psoriasis Area and Severity Index (PASI 90) compared to 50% with ustekinumab and 5% with placebo in patients with moderate-to-severe chronic plaque psoriasis. An Investigator Global Assessment (IGA) score of clear or almost clear (IGA 0/1) was achieved by 84% of bimekizumab patients compared to 53% with ustekinumab and 5% with placebo. In the 16-week, 435 patient, Phase III, BE READY trial, 91% of patients treated with bimekizumab achieved PASI 90 and 93% achieved IGA of 0/1 compared to 1% and 1% with placebo in patients with moderate-to-severe chronic plaque psoriasis. Regulatory Update
The FDA accepted the NDA for Iterum Therapeutics’ oral sulopenem etzadroxil/probenecid for the treatment of uncomplicated urinary tract infections in patients with a quinolone non-susceptible pathogen and set a PDUFA date for 7/25/2021. The FDA extended the review date for aducanumab by three months to allow additional time to review new data Biogen has submitted to satisfy an FDA information request. The PDUFA date is 6/7/2021. The FDA granted Junshi Biosciences’ toripalimab Fast Track status for the treatment of mucosal melanoma. ICER estimated the annual cost for inclisiran to be $3,600 to $6,000 a year to be cost-effective. The range for inclisiran, a PCSK9 RNA silencing drug, is similar to the price for two PCSK9 monoclonal antibodies, evolocumab at $5,400 and alirocumab at $5,850 Announced Research Updates Agios announced that in the 24-week, 27 patient, Phase III, open-label, ACTIVATE trial, 37% of patients treated with mitapivat achieved at least a 33% reduction in the number of units of red blood cells (RBC) transfused compared to the patient’s historical RBC transfusion total in patients with Pyruvate Kinase Deficiency. BeiGene announced results from the 512 patient, open-label, Phase III, Chinese RATIONALE 302 trial, where treatment with tislelizumab improved overall survival compared to investigator’s choice of paclitaxel, docetaxel or irinotecan in patients with advanced unresectable or metastatic esophageal squamous cell carcinoma. Chi-Med announced final results from the Phase Ib, open-label TATTON trial, where treatment with osimertinib plus savolitinib resulted in an overall response rate (ORR) of 33% in patients who received a prior third-generation EGFR TKI, a 65% ORR in patients who did not have a prior third-generation EGFR TKI and were T790M-negative and a 67% ORR in patients who had no prior third-generation EGFR TKI and were T790M-positive. Incyte announced that in the 94-patient, Phase II, open-label, POD1UM-202 trial, treatment with retifanlimab resulted in an objective response rate of 13.8% in patients with locally advanced or metastatic squamous cell carcinoma of the anal canal, who progressed on, or are intolerant of, platinum-based chemotherapy. LSKB and Hengrui announced that in a 31 patient, open-label, Phase II trial, adding apatinib to irinotecan or docetaxel resulted in progression-free survival of 7.43 months in patients with small cell lung cancer. Published Research Updates In a 16-week, 123 patient, Japanese trial, patients treated with omarigliptin achieved a 0.61% decrease in HbA1c compared to a 0.29% increase with linagliptin in patients with type 2 diabetes mellitus. After 16 weeks, all patients received omarigliptin and HbA1c was decreased by 0.57% no matter what patients had received in the first phase of the trial. In the 52-week, 1,755 patient, Phase III, FINCH 1 trial, the percentage of patients that achieved ACR20 at week 12 was 76.6% with filgotinib 200 mg and 69% with filgotinib 100 mg compared to 49.9% with placebo in patients with moderate-to-severe rheumatoid arthritis with an inadequate response to MTX. In a 24 patient, open-label, Phase II trial, treatment with durvalumab, tremelimumab and radiation therapy resulted in an objective response rate of 8.3% in patients with metastatic colorectal cancer. Regulatory Update
The FDA approved vericiguat (Verquvo, Merck, Bayer), on 1/20/2021, to reduce the risk of cardiovascular death and heart failure hospitalization following a hospitalization for heart failure or need for outpatient intravenous (IV) diuretics in adults with symptomatic chronic heart failure with reduced ejection fraction. The FDA approved voclosporin (Lupkynis, Aurinia), on 1/23/2021, for the treatment of lupus nephritis. The FDA approved cabotegravir/rilpivirine injection (Cabenuva, ViiV Healthcare), on 1/21/2021, for the treatment of HIV-1 infection as a replacement for a current antiretroviral regimen in those who are virologically suppressed on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine. Cabotegravir/rilpivirine injection is given once a month. The FDA also approved cabotegravir tablets (Vocabria, ViiV Healthcare). The tablets are taken once a day in combination with oral rilpivirine for one month prior to initiating cabotegravir/rilpivirine long-acting injection to ensure the combination is well-tolerated. The FDA accepted the NDA for odevixibat for the treatment of pruritus in patients with progressive familial intrahepatic cholestasis and set a PDUFA date for 7/20/2021. A site inspection by the FDA has delayed approval of GSK’s dostarlimab. GSK had expected the drug to be approved by the end of 2020, but travel restrictions due to COVID-19 has delayed an inspection of the manufacturing facility. A date has not been set for the inspection or a new PDUFA target. The FDA granted toripalimab Fast Track status as a first-line treatment of mucosal melanoma. Announced Research Updates LSKB announced that in a 30 patient, open-label, Phase II trial, treatment with camrelizumab plus apatinib resulted in a 43.3% overall response rate as second line therapy for Chinese patients with advanced esophageal squamous cell carcinoma. GSK announced data from 106 patients enrolled in cohort F of the open-label, Phase I, GARNET trial, where treatment with dostarlimab resulted in a 38.7% objective response rate in patients with deficient mismatch mutation repair (dMMR) or POLEmut non-endometrial solid tumors. Roche announced that in two 48-week, Phase III trials, which included the 671 patient TENAYA Trial and the 651 patient LUCERNE trial, the change in BCVA from treatment with faricimab, at dosing intervals from eight to 16-weeks, was non-inferior to aflibercept given every eight weeks in patients with neovascular age-related macular degeneration. Almost half (45%) of people in both trials were treated every 16-weeks with faricimab. Published Research Updates In a 3-month, 500 patient, Phase III trial, VM202 did not improve the 24-hour NRS pain score compared to placebo in patients with painful diabetic peripheral neuropathy. In an extension of the 500 patient, Phase III trial, 101 patients were followed for 12-months and VM202 decreased the 24-hour NRS pain score compared to placebo in patients with painful diabetic peripheral neuropathy. Greater pain reduction was found in patients not receiving gabapentin or pregabalin. In the 56 patient, open label Phase I, NAVIGATOR trial, treatment with avapritinib resulted in an 91% overall response rate (ORR) in patients with gastrointestinal stromal tumors and a PDGFRA D842V-mutations. In a 34-week, 112 patient open label extension of the OASIS trial, 84 patients received 2 mg of etrasimod during the extension study with 64% achieving a clinical response, 33% achieving clinical remission and 43% demonstrated an endoscopic improvement. Patients that achieved a clinical response, clinical remission, or endoscopic improvement at week 12 maintained the outcome to the end of treatment in 85%, 60%, or 69% of patients, respectively. In a 24-week, 33 patient, Japanese trial, patients treated with omarigliptin achieved a 0.2% decrease in HbA1c compared to a 0.4% increase with linagliptin in patients with type 2 diabetes mellitus. In a 138 patient, Phase IV trial, treatment with carbetocin decreased blood loss during surgery by 184 ml compared to placebo in women undergoing abdominal myomectomy. In a 138 patient, Phase III trial, treatment with ceftobiprole resulted in 95.7% of patients achieving early clinical response at day four and 90.4% achieving clinical cure compared to 93.2% and 97.7% with placebo in pediatric patients with pneumonia. In a 12-week, 45 patient, Phase II trial, treatment with elafibranor resulted in a 48.3% decrease in serum alkaline phosphatase with 80 mg and a 40.6% decrease with 120 mg compared to a 3% increase with placebo in patients with primary biliary cholangitis that had an inadequate response to ursodeoxycholic acid. In a 124 patient, Phase Il trial, treatment with adavosertib plus gemcitabine resulted in progression free survival of 4.6 months compared to 3 months with gemcitabine alone in patients with p53 tumor suppressor gene (TP53)-mutated ovarian cancer. In the 190 patient, Phase II, open-label, POLARIS-02 trial, treatment with toripalimab resulted in an objective response rate of 20.5% in Chinese patients with recurrent or metastatic nasopharyngeal carcinoma. Regulatory Update
The FDA accepted the NDA for finerenone for the treatment of chronic kidney disease in patients with type 2 diabetes, suggesting a PDUFA date of 7/12/2021. The FDA designated ligelizumab a Breakthrough Therapy for the treatment of chronic spontaneous urticaria in patients who have an inadequate response to H1-antihistamine treatment. The FDA granted padeliporfin a Fast Track designation for the treatment of low-grade and unifocal high-grade Upper Tract Urothelial Cancer. Announced Research Updates Mesoblast announced that in the 30-month, 537 patient, Phase III, DREAM-HF trial, treatment with a single dose of rexlemestrocel-L resulted in a 20.6% incidence of cardiac death, heart attack or stroke compared to 30% incidence with placebo in patients with chronic heart failure with reduced left ventricular ejection fraction, that were receiving optimal oral therapy. Published Research Updates In a 162 patient, Phase II, open-label trial, treatment with olmutinib resulted in an objective response rate of 46.3% in patients with T790M-positive non-small cell lung cancer (NSCLC) after treatment with an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). In the 96-week, 38 patient, Phase III, RESCUE trial, the eyes treated with lenadogen nolparvovec had an improvement in best corrected visual acuity of 10 letters on the ETDRS scale compared to a 9 letter gain in the eyes that received sham injection in patients with Leber Hereditary Optic Neuropathy. In the 12-week, 88 patient, dose-ranging, Phase II STARS trial, 66.7% of patients treated with gaboxadol reduced their Clinical Global Impressions-Improvement scale (CGI-I) score compared to 39.3% with placebo in patients with Angelman syndrome. A post-hoc analysis examined the CGI-I score to determine the number of patients that were very much improved or much improved and found that 32.1% of patients that received gaboxadol once daily reached this threshold compared to 7.1% of placebo patients. There was not a significant improvement compared to placebo with gaboxadol twice daily. In a 48-week, 75 patient, Phase II trial, patients treated with bimagrumab had a 20.5% decrease in total body fat mass compared to a 0.5% decrease with placebo in patients with obesity and type 2 diabetes. In the 52-week, 1,252 patient, Phase III, FINCH 3 trial, the percentage of patients that achieved ACR20 at 24 weeks was 81% with filgotinib 200 mg plus methotrexate and 80% with filgotinib 100 mg plus methotrexate compared to 71% with methotrexate alone in patients with moderate-to-severe rheumatoid arthritis naive to methotrexate. There was no difference between the number of patients that achieved AR20 with filgotinib 200 mg alone compared to methotrexate alone. Regulatory Update
The FDA designated tiragolumab in combination with atezolizumab, a Breakthrough Therapy for the treatment of metastatic non-small cell lung cancer with high PD-L1 expression with no EGFR or ALK genomic tumor aberrations. Announced Research Updates Sarepta announced interim data from 20 patients enrolled in a 48-week, 41 patient, Phase II trial, where SRP-9001 resulted in micro-dystrophin expression of 28.1% at 12-weeks. At 48-weeks, treatment with SRP-9001 improved the NSAA score by 1.7 points in the 20 treated patients, but the improvement was not statistically significant compared to a 0.9 point improvement in 21 placebo patients. The 41 patients enrolled in the study were between the ages of 4 to 7 at enrollment. Loncastuximab tesirine is available through an expanded access program (EAP) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Information on the EAP on be accessed at: https://adctherapeutics.com/expanded-access-program/ Loxo announced that in the 323 patient, Phase I/II, open-label, dose-ranging, BRUIN trial, treatment with LOXO-305 resulted in an overall response of 52% for mantle cell lymphoma (MCL), 68% for MCL and Waldenström macroglobulinemia, 75% for Richter transformation, 50% for follicular lymphoma, 24% for diffuse large B-cell lymphoma, and 22% for marginal zone lymphoma. Published Research Updates In a 42-day, 281 patient, Phase III trial, 53.9% of patients treated with sofpironium improved their Hyperhidrosis Disease Severity Scale to two or less and had a 50% or more reduction in gravimetric sweat production compared to 36.4% that received placebo in Japanese patients with axillary hyperhidrosis. Regulatory Update
The FDA approved ansuvimab (Ebanga, Ridgeback Biotherapeutics), on 12/21/2020, for the treatment for Zaire ebolavirus (Ebolavirus) infection in adults and children. The FDA approved vibegron (Gemtesa, Urovant Sciences), on 12/23/2020, for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults. The FDA rejected arbaclofen due to inadequate justification for the statistical analysis of a primary endpoint (TNmAS-MAL scores at Day 84) in a pivotal trial. The FDA has recommended a new efficacy study be performed. In November 2020, Voyager paused the RESTORE-1 trial when the data safety and monitoring board (DSMB) requested time to analyze MRI imaging abnormalities. The FDA placed a hold on the RESTORE-1 trial in December 2020 due to these abnormalities. Chi-Med initiated a rolling NDA in December 2020 for surufatinib as a treatment of advanced neuroendocrine tumors and plans to complete the submission in the first half of 2021. The EMA approved ViiV Healthcare’s cabotegravir injection in combination with rilpivirine for the treatment of HIV-1 infection in adults who are virologically suppressed. Cara submitted an NDA for difelikefalin, for the treatment of moderate-to-severe pruritus in hemodialysis patients, in December 2020. The FDA designated Immunicum’s Ilixadencel an Orphan Drug for the treatment of hepatocellular carcinoma. Announced Research Updates Amgen and AstraZeneca announced that in the 48-week, 150 patient, Phase III SOURCE trial, treatment with tezepelumab did not reduce daily oral corticosteroids (OCS), without loss of asthma control, compared to placebo in patients with severe asthma who require continuous treatment with inhaled corticosteroids plus long-acting beta2-agonists, and chronic treatment with maintenance OCS. BioMarin announced one-year data from a 119 patient extension of a 121 patient, Phase III trial, where patients treated with vosoritide achieved an increase in height of 1.79 cm more than placebo in children with achondroplasia. ChemoCentryx and VFMCRP announced that in the 26-week, 88 patient, Phase II ACCOLADE trial, treatment with avacopan improved the C3G Histologic Index for Disease Activity by 2% compared to a 38% worsening with placebo in patients with C3 Glomerulopathy. Supernus announced that in a 6-week, 374 patient, Phase III trial, viloxazine decreased the ADHD Investigator Symptom Rating Scale (AISRS) score by 15.5 points compared to an 11.7 point decrease with placebo in adults (age 18 to 65) with attention deficit hyperactivity disorder. Aprea Therapeutics announced that in a 154 patient, Phase III trial, treatment with eprenetapopt plus azacitidine did not improve the complete remission rate compared to azacitidine alone in patients with TP53 mutant myelodysplastic syndromes. Published Research Updates In an 11.9-month interim analysis of a 412 patient, Phase III, open-label trial, carboplatin/pemetrexed/camrelizumab followed by pemetrexed/camrelizumab maintenance resulted in progression free survival (PFS) of 11.3 months compared to 8.3 months with carboplatin/pemetrexed followed by pemetrexed alone in Chinese patients with in non-small cell lung cancer. Regulatory Update
The FDA approved tirbanibulin (Klisyri, Athenex), on 12/15/2020, for the treatment of actinic keratosis on the face or scalp. The FDA approved margetuximab (Margenza, MacroGenics), on 12/17/2020, to be given in combination with chemotherapy, for the treatment of metastatic HER2-positive breast cancer in patients who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. The drug was approved with a Boxed Warning regarding the potential for left ventricular dysfunction and embryo-fetal toxicity. MacroGenics anticipates availability of margetuximab in March of 2021. The FDA approved relugolix (Orgovyx, Myovant Sciences) on 12/18/2020, for the treatment of advanced prostate cancer. The FDA has delayed approval of Novartis’ inclisiran because travel restrictions have delayed the inspection of the manufacturing plant. A new PDUFA date has not been announced. Amgen submitted a BLA for sotorasib for the treatment of metastatic non-small cell lung cancer with a KRAS G12C mutation. Gilead and Galapagos are discontinuing development of filgotinib for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and non-infectious uveitis in the U.S. Gilead will continue to develop filgotinib for the treatment of Crohn’s Disease, while Galapagos will develop the drug for ulcerative colitis. Gilead returned co-marketing and development rights for filgotinib in Europe to Galapagos. The changes were made due to concerns by the FDA on testicular toxicity with the highest dose of filgotinib. The FDA placed a clinical hold on UniQure’s etranacogene dezaparvovec clinical trials after a preliminary diagnosis of hepatocellular carcinoma was made in one patient enrolled in the Phase III HOPE-B trial. The EMA has granted Orphan status to Acceleron Pharma’s sotatercept for the treatment of patients with pulmonary arterial hypertension. Announced Research Updates Roche announced that in the 255 patient arm of the Phase II, IPATunity130 trial, treatment with ipatasertib added to paclitaxel did not improve progression free survival compared to paclitaxel alone (7.4 vs 6.1 months) in patients with locally advanced or metastatic triple-negative breast cancer with alterations to the PIK3CA, AKT1 and PTEN genes. VTV announced that in the 6-month, 43 patient, Phase II, ELEVAGE trial, azeliragon did not improve cognition (ADAS-cog14) compared to placebo in patients with mild probable Alzheimer’s Disease. AB Science announced that in a 24-week, 718 patient, Phase IIb/III trial, treatment with masitinib improved the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) compared to placebo in patients with mild to moderate Alzheimer’s disease who were receiving a cholinesterase inhibitor (donepezil, rivastigmine or galantamine) and/or memantine. Daiichi Sankyo announced that in a 14-week, 274 patient, Phase III trial, treatment with mirogabalin reduced pain more than placebo in patients with central neuropathic pain after spinal cord injury. Roche announced that in two 1-year, Phase III trials, which included the 951 patient RHINE Trial and the 940 patient YOSEMITE trial, the change in best-corrected visual acuity from treatment with faricimab, at dosing intervals from eight to 16-weeks, was non-inferior to aflibercept given every eight weeks in patients with diabetic macular edema. Published Research Updates In the 150 patient Phase II, ProCAID trial, adding capivasertib to docetaxel plus prednisone did not improve progression free survival in patients with metastatic castration-resistant prostate cancer. In a 12-week, 156 patient, Phase II trial, treatment with praliciguat did not improve the urine albumin to creatinine ratio compared to placebo in patients with type 2 diabetes and diabetic nephropathy. Daiichi Sankyo announced that in a 14-week, 274 patient, Phase III trial, treatment with mirogabalin reduced pain more than placebo in patients with central neuropathic pain after spinal cord injury. |
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