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Regulatory Update
The FDA approved ozanimod (Zeposia, Bristol Myers Squibb) on 3/25/2020 for the treatment of adults with relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. BMS announced it would delay the launch for an unspecified time due to the COVID-19 pandemic. Pricing will be announced shortly before launch. The FDA accepted the NDA for bupivacaine hydrochloride collagen-matrix for the management of postsurgical pain after open inguinal hernia surgery and set a PDUFA date of 8/26/2020. The FDA requested additional information on beta beglogene darolentivec manufacturing; therefore Bluebird has delayed submission of a BLA to mid-2021. Announced Research Updates VBL Therapeutics announced positive interim results from 60 patients enrolled in the 400 patient, Phase III OVAL trial, where treatment with ofranergene obadenovec plus paclitaxel demonstrated a 58% overall response rate in patients with platinum-resistant ovarian cancer. Inovio announced 6-month interim results from 20 patients enrolled in an 88-week, Phase II trial, where treatment with VGX-3100 resulted in an overall decrease in the number of lesions in 15/20 patients with 10/20 demonstrating clearance of HPV-16/18 associated precancerous lesions in adults with precancerous anal dysplasia caused by HPV-16 and/or HPV-18. MyoKardia announced that in the 16-week, 59 patient, Phase II MAVERICK-HCM trial, treatment with mavacamten resulted in a 53% reduction in serum NT-proBNP compared to 1% reduction with placebo in patients with symptomatic, non-obstructive hypertrophic cardiomyopathy. Published Research Updates In the Phase III, ARCTIC trial, tremelimumab added to durvalumab improved overall survival and progression-free survival in heavily pretreated patients with metastatic non-small cell lung cancer. In a 15-week, 57 patient, Phase II trial, treatment with tavapadon reduced the MDS-UPDRS Part III score by 9.0 points compared to a 4.3 point decrease with placebo in patients with early-stage Parkinson's disease. In a 70 patient trial, levosimendan was comparable to milrinone on myocardial function after pediatric cardiac surgery. In the 146 patient, Phase IIb, open-label, FIGHT-202 trial, treatment with pemigatinib resulted in an overall response in 38/107 patients with cholangiocarcinoma with FGFR2 fusions or rearrangements. In the 371 patient, Phase III BRIGHTE trial, fostemsavir was added to a failing antiviral regimen in patients with resistant infections or intolerance to a regimen. After 8 days the HIV-1 RNA level was 0.79 log10 copies per milliliter in the fostemsavir group and 0.17 log10 copies in the placebo group. At 48 weeks 54% of randomized patients and 38% of non-randomized patients maintained virologic suppression (<40 c/mL). In a 5,050 patient, Phase III VICTORIA trial, 35.5% of patients treated with vericiguat experienced the primary outcome (composite of death from cardiovascular causes or first hospitalization for heart failure) compared to 38.5% in the placebo group in patients with chronic heart failure and an ejection fraction of less than 45% that were receiving guideline-based medical therapy. In the Phase III, BETonMACE trial, apabetalone added to standard of care did not reduce major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or stroke) compared to placebo in high-risk patients with type 2 diabetes, recent acute coronary syndrome, and low HDL cholesterol. Regulatory Update
The FDA canceled a May advisory committee meeting when questions arose regarding the Viaskin Peanut patch’s adhesion and efficacy if the patch is not fully adhered. Aimmune is in the process of providing data on the question. The PDFUA date has not been changed. Mallinckrodt completed a rolling NDA for terlipressin for the treatment of patients with hepatorenal syndrome type 1 in March 2020. Canada approved cabotegravir and rilpivirine injection for the treatment of HIV-1 infection. Announced Research Updates Merck announced that in the 12-week, 732 patient, Phase III, COUGH-1 trial, treatment with gefapixant 45 mg BID reduced the 24-hour coughs per hour average more than placebo in patients with refractory or unexplained chronic cough. Merck announced that in the 24-week, 1,317 patient, Phase III, COUGH-2 trial, treatment with gefapixant 45 mg BID reduced the 24-hour coughs per hour average more than placebo in patients with refractory or unexplained chronic cough. Treatment with gefapixant 15 mg BID did not differ from placebo in both the COUGH-1 and COUGH-2 trials. Pfizer announced that in a 16-week, 837 patient, Phase III, JADE COMPARE trial, more patients treated with abrocitinib 100 mg and 200 mg achieved an IGA score of clear or almost clear skin, had a 2 point or > improvement in their IGA score and had more patients achieve at least a 75% or greater improvement in their Eczema Area and Severity Index (EASI) score compared to placebo in patients with moderate to severe atopic dermatitis receiving topical therapy. Pfizer plans to submit an NDA for abrocitinib by the end of 2020. AstraZeneca announced that in the 805 patient, Phase III, open-label, CASPIAN trial, the addition of tremelimumab to durvalumab plus standard-of-care chemotherapy did not improve overall survival compared to durvalumab plus standard-of-care chemotherapy in patients with extensive-stage small cell lung cancer. Published Research Updates In a 52 patient, Phase II trial, treatment with rivoceranib and carboplatin-paclitaxel as first-line chemotherapy demonstrated an ORR of 64.3% compared to 33.3% with rivoceranib and concurrent chemo-brachytherapy in patients with recurrent and advanced cervical cancer. A subgroup analysis of 8,236 diabetic patients enrolled in the 6-month, Phase III, ACCELERATE trial, found that treatment with evacetrapib increased HDL by 131% and lowered LDL by 32%. HbA1c was lower than placebo (7.08% vs 7.15%), but there was no difference in the primary composite endpoint of cardiovascular death, myocardial infarction, stroke, revascularization, and hospitalization for unstable angina compared to placebo. In the 510-day, 482 patient, Phase III, ORION-9 trial, treatment with inclisiran lowered LDL by 39.7% compared to an 8.2% increase with placebo in patients with heterozygous familial hypercholesterolemia. In the 510-day, 1,561 patient, Phase III, ORION-10 trial, the placebo adjusted reduction in LDL with inclisiran was 52.3% in patients with atherosclerotic cardiovascular disease and elevated LDL despite maximum tolerated dose of statin. In the 510-day, 1,617 patient, Phase III, ORION-11 trial, the placebo adjusted reduction in LDL with inclisiran was 49.9% in patients with atherosclerotic cardiovascular disease or risk equivalents and elevated LDL despite maximum tolerated dose of statin. In a 71 patient, Phase II trial, treatment with Lu-PSMA-617 plus dexamethasone did not improve PSA compared to Lu-PSMA-617 monotherapy in patients with metastatic castration-resistant prostate cancer. In a 50 patient, Phase II, open label trial, treatment with selumetinib resulted in a 70% objective response in pediatric patients with neurofibromatosis type 1 and inoperable plexiform neurofibromas. In a 30-patient, Phase II, open-label Chinese trial, treatment with rivoceranib plus vinorelbine resulted in an overall response rate of 36.7% in patients with wild-type advanced non-small-cell lung cancer. Viltolarsen is available in an expanded access program for patients with Duchenne muscular dystrophy amenable to exon 53 skipping that meet criteria. In a 48-month, 562 patient, Phase II trial, mean titres were 378 in two-dose, 421 in one-dose, 719 in one-dose plus 1-year booster compared to 100 with placebo in children ages two to 17 years living in dengue-endemic areas. Virologically confirmed dengue was recorded in 2% of TAK-003 and 7% of placebo patients. In the 18-month, 20,099 patient, Phase III, TIDES trial, 80.2% of patients that received TAK-003 developed a virologically confirmed dengue compared to placebo in children and adolescents ages four to 16 years living in dengue-endemic areas. Regulatory Update
The FDA accepted the NDA for Athenex/Almirall’s tirbanibulin for the treatment of actinic keratosis and set a PDUFA date of 12/30/2020. The FDA designated F2G’s olorofim as an Orphan Drug for the treatment of invasive aspergillosis and lomentospora/scedosporium infections. Announced Research Updates ORMD announced that in a 12-week, 269 patient, Phase IIb dose-ranging trial, treatment with oral insulin reduced HbA1c by 0.6% with 32 mg once daily and twice daily compared to placebo in patients with type 2 diabetes receiving metformin with up to two additional oral antihyperglycemic agents. Giving the dose three times per day did not improve HbA1c more than placebo. AZ announced that in a Phase III, open-label trial, treatment with cediranib plus olaparib did not improve progression-free survival compared to platinum-based chemotherapy in patients with platinum-sensitive relapsed ovarian cancer. Published Research Updates In the 48-week, 877 patient, Phase III, STELLAR-4 trial, treatment with selonsertib 18 mg or 6 mg did not improve liver fibrosis by one stage or more without disease worsening compared to placebo (10-12% vs 13%) in patients with compensated cirrhosis due to NASH. In the 48-week, 803 patient, Phase III, STELLAR-3 trial, treatment with selonsertib 18 mg or 6 mg did not improve liver fibrosis by one stage or more without disease worsening compared to placebo (13-14% vs 13%) in patients with stage 3 fibrosis from NASH. In the 14-week, 610 patient, Phase III, open-label, SUMMIT-07 trial, loxicodegol exhibited a low rate and severity of opioid withdrawal compared to placebo as measured by Clinical Opiate Withdrawal Scale (COWS) - 2.3% vs .05%; Subjective Opiate Withdrawal Scale (SOWS) - no difference; Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS) - 2.9% vs 3.7% in patients with chronic low back pain. In a 48-week, 40 patient, Phase II trial, patients with chronic HBV who tested HBV e-antigen negative were treated for 48 weeks with tenofovir disoproxil fumarate, pegylated interferon alfa-2a and either REP 2139 or REP 2165. The two investigational drugs were equivalent in efficacy. At 48 weeks HBsAg levels were 0.05 IU/mL or lower in 24/40 patients. 48 weeks after the end of treatment virologic control persisted in 13/40 participants. In a 115 patient, Phase II trial, trebananib plus bevacizumab had a worse 6-month PFS compared to bevacizumab monotherapy in patients with recurrent glioblastoma. In a 234 patient, Phase II trial, treatment with olanzapine plus samidorphan did not reduce the time to the first event of exacerbation of disease symptoms compared to olanzapine monotherapy in patients with schizophrenia and alcohol use disorder. A 22.7 month interim analysis of data from 843 patients participating in a Phase III, extension, open-label trial, showed that treatment with peficitinib resulted in ACR20/50/70 in 78.9%, 61.4%, and 42.7% of Asian patients with rheumatoid arthritis. Regulatory Update
The FDA approved isatuximab (Sarclisa, Sanofi) on 3/2/2020 to be given in combination with pomalidomide (Revlimid, Celgene) and dexamethasone for the treatment of multiple myeloma in patients that received two or more prior therapies including lenalidomide and a proteasome inhibitor. Sanofi set WAC for a 5 ml vial of isatuximab at $650 and $3,250 for a 25 ml vial. The FDA approved osilodrostat (Isturisa, Novartis) on 3/6/2020 for the treatment of adults with Cushing's disease who either are candidates for pituitary gland surgery or in whom the disease persists after surgery. Redhill launched amoxicillin, omeprazole, rifabutin (Talicia) on 3/9/2020 at a WAC of $650 for 168 capsules. Omeprazole, amoxicillin and rifabutin was approved on 11/5/2019 for the treatment of Helicobacter pylori infection in adults. The FDA accepted the NDA for Urovant/Kyorin/Merck’s vibegron for the treatment of overactive bladder and set a PDUFA date of December 26, 2020. The FDA accepted the resubmitted NDA for Trevena’s oliceridine as a treatment for moderate-to-severe acute pain and set a PDUFA date of 8/7/2020. The FDA accepted the BLA for Pfizer’s tanezumab, in March 2020, for the treatment of chronic osteoarthritis pain in patients who have experienced inadequate pain relief with other analgesics and set a PDUFA date in December 2020. The FDA granted a Rare Pediatric Disease designation to Stealth BioTherapeutics’ elamipretide for the treatment of Barth syndrome. Mallinckrodt initiated a rolling submission NDA for terlipressin for the treatment of patients with hepatorenal syndrome type 1 in March 2020. Janssen submitted an MAA for ponesimod for treatment of adults with relapsing-remitting multiple sclerosis. Announced Research Updates AstraZeneca announced that in the 1,126 patient, Phase III, open-label, DANUBE trial, neither durvalumab plus tremelimumab nor durvalumab monotherapy improved overall survival compared to standard-of-care chemotherapy in patients with unresectable stage IV bladder cancer. Published Research Updates In a 279 patient trial, there was no difference in mortality in patients treated with levosimendan compared to intra-aortic balloon counterpulsation in patients with poor left ventricular function undergoing coronary artery bypass grafting (CABG) with ejection fraction less than 35%. In a 65 patient, 4-day, Phase II, open-label trial, treatment with terlipressin reduced portal venous pressure by 1.5 mmHg in patients with portal vein pressure >12 mmHg after hepatectomy. In the 48-week, 616 patient, Phase III ATLAS Trial, 1.6% of patients that received a monthly IM injection of cabotegravir and rilpivirine had an HIV-1 RNA of 50 copies/mL or > compared to 1% of patients that continued a standard daily thee drug oral regimen in patients with plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy. In the 48-week, 566 patient, Phase III FLAIR trial, patients were treated with 20 weeks of daily oral induction therapy with dolutegravir-abacavir-lamivudine, then randomized to monthly IM injection of cabotegravir and rilpivirine or continuation of dolutegravir-abacavir-lamivudin. After 48 weeks 2.1% of patients that received cabotegravir/rilpivirine monthly had an HIV-1 RNA of 50 copies/mL or > compared to 2.5% of patients that continued dolutegravir-abacavir-lamivudin in patients with with HIV-1 infection who had not previously received antiretroviral therapy. Regulatory Update
The FDA approved rimegepant (Nurtec ODT, Biohaven) on 2/27/2020 for the acute treatment of migraine with or without aura in adults. Biohaven expects to have rimegepant available in early March. Rimegepant will compete with the triptans, ubrogepant, and lasmiditan. The gepants (ubrogepant and rimegepant) and lasmiditan do not cause vasoconstriction and may be an alternative when patients do not tolerate triptans. Merck abandoned work on two early gepants due to concerns over elevation in transaminase levels with telcagepant, but ubrogepant and rimegepant have not demonstrated liver toxicity. The FDA approved amisulpride (Barhemsys, Acacia Pharma) on 2/26/2020 for the prevention and treatment of PONV in adult patients. The FDA’s Oncologic Drugs Advisory Committee voted 2-13 against recommending approval of padeliporfin (Tookad, Steba Biotech) for the treatment of adenocarcinoma of the prostate in February 2020. The FDA granted Lysogene/Sarepta’s LYS-SAF302 Fast Track status for the treatment of mucopolysaccharidosis Type IIIA (MPS IIIA). Announced Research Updates Vanda announced that in the 8-week, 341 patient, Phase III, EPIONE trial, tradipitant did not improve the Worst Itch Numeric Rating Scale (WI-NRS) score compared to placebo in patients with atopic dermatitis with chronic pruritus. Menlo announced that in a 10-week, 233 patient, Phase II trial, treatment with selopitant did not improve the Worst Itch Numeric Rating Scale score compared to placebo in patients with chronic pruritus of unknown origin. Published Research Updates ICER reviewed lasmiditan, ubrogepant and rimegepant and found the drugs to be comparable in efficacy, but not as efficacious as triptans. Lasmiditan was found to have higher rates of dizziness and discontinuation. ICER concluded that lasmiditan, ubrogepant and rimegepant would provide a benefit for patients with cardiovascular disease that have a contraindication to triptans, were not helped by triptans or do not tolerate them. ICER estimates that 10-20% more patients have relief from their migraines with the new drugs compared to placebo. Since triptans are available as generics, ICER felt that triptans would provide a greater benefit at a lower cost than lasmiditan, ubrogepant or rimegepant. To reach a threshold of $150,000 per quality-adjusted life year, ICER estimated an annual cost for lasmiditan of $2,800-$3,200 to be cost- effective compared to the annual lasmiditan WAC of $4,610. For ubrogepant and rimegepant, ICER estimated an annual cost of $4,200-$4,600. The annual WAC for ubrogepant is $4,896. No pricing has been established for rimegepant, since the drug is not approved. In the 4-week, 30 patient, Phase III, cross-over, MMPOWER-2 trial, treatment with elamipretide did not improve distance traveled in a six-minute walking test (6MWT) compared to placebo in patients with primary mitochondrial myopathy (PMM). In a 12-week, 253 patient, Phase IIb, dose ranging trial, treatment with gefapixant 50 mg reduced the 12-week Awake Objective Cough Frequency by 37% compared to placebo in patients with chronic cough. Treatment with gefapixant 7.5 mg or 20 mg did not differ from placebo. In a 12-week, 287 patient, Phase IIb, dose ranging trial, treatment with fezolinetant reduced the vasomotor symptom (VMS) score by -0.2 to -0.6 point and the VMS frequency by -1.8 to -2.6 events per day compared to placebo in patients with moderate to severe vasomotor symptoms. In a 16-week, 280 patient, Phase Ib trial, lebrikizumab improved the EASI score by 62.3% in patients receiving 125 mg every four weeks, 69.2% with 250 mg every four weeks and 72.1% for patients receiving 250 mg every two weeks compared to a 41.1% improvement with placebo in patients with moderate-to-severe atopic dermatitis. In a 12.5 month, 217 patient, Phase II, open-label trial, treatment with camrelizumab resulted in an overall response in 14.7% of patients with hepatocellular carcinoma. |
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