Pipeline News and Updates
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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. Regulatory Update
The FDA notified BMS of problems with sterilization procedures at the Washington plant that will manufacturer lisocabtagene maraleucel. The FDA accepted the NDA for Scynexis's ibrexafungerp for the treatment of vulvovaginal candidiasis and set a PDUFA date for 6/1/2021. The FDA accepted the NDA for Chimerix’s brincidofovir for the treatment of smallpox and set a PDUFA date for 4/7/2021. The FDA accepted the NDA for reltecimod for the treatment of suspected organ dysfunction or failure in patients 12 years or older with necrotizing soft tissue infection, in conjunction with surgical debridement, antibiotic therapy, and supportive care. A PDUFA date has been set for 9/30/2021. The FDA granted a Fast Track Designation to Immunicum’s Ilixadencel for the treatment of Gastrointestinal Stromal Tumors (GIST). The FDA designated Amgen’s sotorasib a Breakthrough Therapy, for the treatment of locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutation. The FDA granted mavorixa a Fast Track designation for the treatment of WHIM syndrome. The EMA has approved inclisiran for the treatment of hypercholesterolemia and mixed dyslipidemia. Sanofi resumed fitusiran clinical trials in December 2020 with an adjusted dosing regimen designed to reduce adverse effects. Announced Research Updates ADC announced interim results from 18 patients enrolled in the Phase I/II, open-label, LOTIS 3 trial, where treatment with loncastuximab tesirine plus ibrutinib resulted in an ORR of 58.6% in patients with relapsed or refractory DLBCL and 83.3% in patients with mantle cell lymphoma (MCL). Patients with non-germinal center B-cell DLBCL had an ORR of 66.7% compared to 20% in germinal center B-cell DLBCL patients. Oncopeptides announced interim data from 46 patients enrolled in the Phase II, open-label, ANCHOR trial, where patients treated with melflufen and dexamethasone plus daratumumab achieved an ORR of 73%, while patents treated with melflufen and dexamethasone plus bortezomib achieved a 62% ORR in patients with relapsed refractory multiple myeloma. Gilead announced interim results from 64 patients enrolled in a Phase I, open-label trial, where treatment with magrolimab plus azacitidine resulted in a 63% objective response rate (ORR) in patients with myelodysplastic syndrome and a 63% ORR in patients with acute myeloid leukemia, who are ineligible for induction chemotherapy. Lilly announced that in the 40-week, 478 patient, Phase III, SURPASS-1 trial, treatment with tirzepatide lowered HbA1c 1.87% with 5 mg, 1.89% with 10 mg and 2.07% with 15 mg compared to a 0.04% increase with placebo in patients with type 2 diabetes. Treatment with tirzepatide also lead to weight loss of 7 kg with 5 mg,7.8 kg with 10 mg and 9.5 kg with 15 mg compared to a 0.7 Kg loss with placebo. Biosight announced interim data from 31 patients enrolled in a Phase IIb trial, where treatment with aspacytarabine resulted in a 32% complete response rate in patients with acute myeloid leukemia who are not eligible for standard induction chemotherapy due to advanced age or comorbidities. AlloVir announced that in the six-week, Phase II, CHARMS trial, patients treated with ALVR105 achieved a 93% clinical response (defined as complete response - viral load returning to normal range and resolution of clinical signs/symptoms or a partial response (50% or > decrease in viral load and/or 50% improvement of clinical signs/symptoms) in allo-hematopoietic stem cell transplantation patients with at least one treatment-refractory infection. Roche announced interim results from 62 patients enrolled in a Phase I/Ib, open-label trial, where treatment with mosunetuzumab induced a complete response in 32/62 patients with relapsed or refractory follicular lymphoma. Inovio announced that in a 6-month, 22 patient, Phase II trial, treatment with VGX-3100 resulted in resolution of HPV-16/18-associated precancerous anal lesions in 11/22 patients with high grade anal squamous intraepithelial lesions caused by HPV-16/18. TG Therapeutics announced that in two 96-week Phase III trials involving 1,094 patients treatment with an intravenous infusion of ublituximab every six months resulted in a 60% annualized relapse rate (ARR) in ULTIMATE I and a 50% ARR in ULTIMATE II compared to daily oral teriflunomide in patients with relapsing forms of multiple sclerosis. Apellis announced that in a 36-week, 77 patient, open-label extension of the Phase III PEGASUS trial, patients that continued pegcetacoplan maintained a hemoglobin increase of 2.7 g/dL and patients switched from eculizumab experienced a similar increase. Published Research Updates In a 24-week, 42 Japanese patient, Phase III, open label trial, treatment with vadadustat resulted in a mean Hb of 11.35 g/dL in patients with peritoneal dialysis-dependent CKD. In a 130-week, 69 peanut-allergy patient, Phase II trial, patients received 52-weeks of Viaskin Peanut 100 mcg, 250 mcg or placebo. After 52-weeks, all patients were switched to 250 mcg of Viaskin Peanut. At 130 weeks, desensitization was achieved in 1/20 placebo-250 mcg patients, 5/24 100 mcg-250 mcg patients and 9/25 participants who received 250 mcg for the full treatment duration. In the 48-week, 1,045 patient, Phase III ATLAS-2M trial, 2% of patients that received IM injection of cabotegravir and rilpivirine every two months had an HIV-1 RNA of 50 copies/mL or > compared to 1% of patients that received the combination monthly, achieving non-inferiority for less frequent dosing. In the 96-week, 37 patient, Phase III, REVERSE trial, lenadogen nolparvovec improved visual acuity from vision nadir by 15 letters in the treated eye, which was a non-significant difference compared to a 13 letter improvement in the eye that received a sham injection in patients with visual loss from Leber hereditary optic neuropathy In a 26-week, 191 patient, open-label extension of a Phase III trial, patients that continued ravulizumab had lactate dehydrogenase (LDH) levels increased by 8.8% and four patients experienced breakthrough hemolysis compared to an LDH increase of 5.8% and one case of breakthrough hemolysis in patients switched from eculizumab to ravulizumab. In the 157 patient, Phase II, open-label, HORIZON trial, treatment with melflufen plus dexamethasone resulted in an overall response rate of 29% in patients with multiple myeloma. Regulatory Update
The FDA approved berotralstat (Orladeyo, BioCryst Pharmaceuticals), on 12/3/2020, for prevention of attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older. BioCryst set WAC at $485,000 per year. Berotralstat is the first oral treatment approved for treatment of HAE. The FDA accepted the NDA from Kadmon for belumosudil for the treatment of chronic graft-versus-host disease and set a PDUFA date for 5/30/2021. The FDA accepted the NDA from BridgeBio Pharma for infigratinib to treat patients with cholangiocarcinoma, which suggests a PDUFA date in April or May 2021. Iterum has submitted an NDA for oral sulopenem etzadroxil/probenecid for the treatment of uncomplicated urinary tract infections in patients with a quinolone non-susceptible pathogen. TG Therapeutics initiated a rolling BLA submission for ublituximab plus umbralisib for the treatment of patients with chronic lymphocytic leukemia. The FDA granted ilixadencel, a Fast Track Designation for the treatment of Gastrointestinal Stromal Tumors (GIST). Agenus began a rolling BLA for balstilimab for the treatment of recurrent/metastatic cervical cancer in September 2020 and plans to complete the submission in the first half of 2021. Announced Research Updates Ovid announced that in the 12-week, 97 patient, Phase III NEPTUNE trial, gaboxadol did not improve the Clinical Global Impression-Improvement-Angelman syndrome (CGI-I-AS) score compared to placebo (0.7 points vs 0.8) in patients with Angelman syndrome. Takeda announced that in the eight-week, 352 patient, Phase III, SOLSTICE trial, more patients treated with maribavir achieved confirmed CMV viremia clearance compared to investigator-assigned treatment (ganciclovir, valganciclovir, foscarnet, or cidofovir) in transplant patients with refractory/resistant CMV infection. AB Science announced that in a 383 patient, Phase III trial, treatment with masitinib plus gemcitabine increased overall survival by 1.8 months compared to gemcitabine alone (13 vs 11.2 months) in patients with unresectable locally advanced or metastatic pancreatic cancer patients with pain at baseline or taking opioids. J&J announced data after 12.4-months in the 97 patient, Phase Ib/II CARTITUDE-1 trial, where ciltacabtagene autoleucel demonstrated an overall response rate of 97% and complete response of 67% in patients with relapsed multiple myeloma. Published Research Updates Interim data from 96 patients enrolled in the 48-week, 420 patient, Phase III, TALENT trial, found that 80.4% of patients treated with weekly albuvirtide plus ritonavir-boosted lopinavir achieved a plasma viral load below 50 copies/mL compared to 66% of patients who received daily lopinavir-ritonavir, tenofovir and lamivudine alone in adults who failed their first antiretroviral regimen and have HIV-1 RNA levels >= 1000 copies/mL. In a 51 patient, Phase II, open-label trial, treatment with umbralisib resulted in progression-free survival of 23.5 months in chronic lymphocytic leukemia patients who are intolerant to prior BTK inhibitors or prior PI3K delta inhibitors. In a 164 patient, Phase II trial, indoximod added to paclitaxel or docetaxel did not improve progression-free survival compared to taxanes alone in patients with ERBB2-negative metastatic breast cancer. In the 40-month, 91 patient, Phase IIb, VITAL trial, treatment with gemogenovatucel-T resulted in recurrence-free survival of 11.5 months compared to 8.4 months with placebo in patients with stage III/IV high-grade serous, endometrioid, or clear cell ovarian cancer. AstraZeneca announced that in the 805 patient, Phase III, open-label, CASPIAN trial, the addition of tremelimumab to durvalumab plus platinum–etoposide did not improve overall survival compared to durvalumab plus platinum–etoposide (10.4 vs 10.5 months), however, durvalumab plus platinum–etoposide did increase overall survival compared to platinum–etoposide (12.9 vs 10.5 months), in patients with extensive-stage small cell lung cancer. In a 12-week, 61 patient, Phase II trial, median ESA usage decreased by 15,000, 15,000, and 33,000 IU/week with 2, 6, and 20 mg doses of ziltivekimab in patients on hemodialysis with inflammation and hyporesponsiveness to ESA therapy. In a 24-week, 299 patient, Phase II trial, imeglimin lowered HbA1c compared to placebo by 0.52% with imeglimin 500 mg, 0.94% with 1000 mg and 1% with 1,500 mg in Japanese patients with type 2 diabetes. Back in February we identified eleven potential blockbusters on track for approval in 2020. At this point, five have been approved and six are in need of additional data from trials before the FDA will grant approval. The five approvals covered the following indications: migraine, relapsing multiple sclerosis (2 drugs), breast cancer, and spinal muscular atrophy.
Read on to review the status of these eleven potential blockbusters:
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