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Pipeline News and Updates
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Risankizumab Approved – ICER Weighs In

4/30/2019

 
Regulatory Updates

The FDA approved risankizumab (Skyrizi, AbbVie) on 4/23/2019 for the treatment of plaque psoriasis. Risankizumab is dosed every 12 weeks after an initial 2 injections. The drug will compete with ixekizumab, tildrakizumab, guselkumab, and secukinumab. ICER has estimated an annual price of $28,800–$42,100 for risankizumab to achieve a long-term cost-effectiveness benchmark of $100,000– $150,000 per QALY. ICER suggested that step therapy approaches may not be appropriate for psoriasis. In an analysis of current data ICER found that risankizumab may be more effective than TNF-blockers, but this is based on grey literature, since risankizumab studies have not been published. AbbVie announced the annual WAC for maintenance dosing of risankizumab is $59,000.

The FDA accepted the BLA for eptinezumab. Alder forecasts approval in May. If approved in 2019, Alder expects to launch the drug in 1Q20 for migraine prophylaxis. 

Genentech’s Risdiplam was granted PRIME status by the EMA for the treatment of Spinal muscular atrophy.

Celgene and Acceleron submitted a BLA and a MAA for luspatercept in April 2019. The drug will be compared to ESA drugs in non-transfusion-dependent beta-thalassemia and in myelofibrosis.

Biogen has decided not to initiate a Phase III trial of aducanumab in the prevention of Alzheimer’s disease.

Fulcrum Therapeutics licensed losmapimod from GSK in April 2019 and plans to develop the drug as a treatment for facioscapulohumeral muscular dystrophy. Fulcrum has an ongoing trial evaluating losmapimod for the treatment of facioscapulohumeral muscular dystrophy.

Announced Research Updates

Gilead announced that 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 1 stage or more without disease worsening compared to placebo in patients with stage 3 fibrosis from NASH.

Published Research Update

In a 24-week, 41 patient, Phase I/II, open label trial, treatment with X4P-001 (X4 Pharmaceuticals) 200 mg BID or 400 mg QD plus axitinib 5 mg BID resulted in an objective response rate of 31.8% in 22 evaluable patients with advanced clear cell renal cell carcinoma.

In the 8-week, 256 patient, Phase IIb, open-label, NEW-HOPE trial, treatment with firibastat (Quantum Genomics) resulted in a 9.5 mmHg decrease in systolic blood pressure and a 4.2 mmHg decrease in diastolic blood pressure in a high-risk diverse hypertensive population.

Two drugs have PDUFA dates in May

4/26/2019

 
Sanofi’s dengue vaccine (Dengvaxia) has a PDUFA date of May 1, 2019.  Dengvaxia is a 3-dose, subcutaneous vaccine for the prevention of malaria. The vaccine was tested in Brazil and the Philippines and was able to prevent 2/3 of cases and prevented 8/10 hospitalizations.  Two large trials found efficacy of around 60%. Two Phase III pediatric trials demonstrated vaccine efficacy of 56.5% and 60.8%, respectively, against symptomatic virologically confirmed dengue. The vaccine appeared to be more effective in older children possibly due to higher baseline seropositivity and potentially a more broadly protective immune response. A four-year follow-up of two Phase II trial involving 1,378 patients found the vaccine demonstrated long-term immunogenicity. Dengvaxia is approved in 5 countries, which include Brazil, Philippines and Mexico. If that patient contracts the viral infection naturally, their immune system could process it as a second infection that is much more severe.  The FDA has granted Dengvaxia a priority review. An analysis by WHO cautioned of an increased risk for severe dengue in seronegative vaccine recipients compared to seronegative non-vaccinated patients, but long-term protection in seropositive individuals is achieved. The FDA’s Vaccines and related Biological Products Advisory Committee voted to recommend approval for Sanofi’s Dengue vaccine for patients 9 to 17 years, but not in adult patients.

Novartis onasemnogene abeparvovec (Avexis) has a PDUFA date for an unspecified date in May 2019. Onasemnogene abeparvovec is a single dose, intravenous Infusion for the treatment of spinal muscular atrophy. Onasemnogene abeparvovec was evaluated In the 20-month, 15 patient, Phase I, START trial, where treatment with the gene therapy resulted in all patients being alive compared to 8% of a historical control group of patients with SMA type 1. At 3-months there was a 15.4 point improvement in the CHOP INTEND score of motor function score in patients treated with onasemnogene abeparvovec compared to a decline in the historical control. Novartis announced interim data from 22 patients in the Phase III, STR1VE trial, where treatment with onasemnogene abeparvovec resulted in a 11.8 point improvement in the CHOP INTEND score at 3 months in patients with SMA type 1. One patient died from respiratory failure, which was deemed to be unrelated to treatment. When approved onasemnogene abeparvovec will compete with nusinersen. Novartis indicated it may price the gene therapy as high as $4-5 million. Using a placeholder cost of $2 million, ICER estimated a cost per QALY for onasemnogene abeparvovec of $243,000 compared to best supportive care. ICER estimated that to be cost effective the cost of onasemnogene abeparvovec would need to be $900,000 to be in a $150,000 of QALY range, or $1.5 million if estimating the cost for each additional year of life gained (LYG) of $150,000.

Investigational Drug Update for the Week Ending April 20, 2019

4/23/2019

 
​Regulatory Updates

The FDA approved hydrogel capsules (Plenity, Gelesis) on 4/14/2019 as a device for weight management in adults with a body mass index (BMI) of 25 - 40 kg/m2, when used together with diet and exercise.

The FDA accepted the BLA and a priority voucher for Novartis’ brolucizumab in April 2019, suggesting a PDUFA date of 10/15/2019. 

The FDA designated Genfit’s elafibranor a Breakthrough Therapy in April 2019 for the treatment of primary biliary cholangitis.

Viela Bio’s inebilizumab was designated a Breakthrough Therapy by the FDA in April 2019 for the treatment of neuromyelitis optica spectrum disorder.

The FDA scheduled an Oncologic Drugs Advisory Committee (ODAC) hearing for 5/14/2019, to review Daiichi Sankyo/Plexxikon’s pexidartinib for the treatment of adult patients with symptomatic tenosynovial giant cell tumor.

The FDA scheduled an Oncologic Drugs Advisory Committee (ODAC) hearing for 5/14/2019, to review Ambit Biosciences Corporation/Daiichi Sankyo’s quizartinib tablets for the treatment of adult patients with relapsed/refractory FLT3-ITD–positive acute myeloid leukemia (AML).

New Trial Results Announced

Alkremes announced that in the 265 patient, 28-week extension of the ENLIGHTEN-2 trial, olanzapine/samidorphan demonstrated no additional weight gain.

Novartis announced interim data from 22 patients in the Phase III, STR1VE trial, where treatment with onasemnogene abeparvovec resulted in a 11.8 point improvement in the CHOP INTEND score at 3 months in patients with SMA type 1. One patient died from respiratory failure, which was deemed to be unrelated to treatment. The Phase III STR1VE is estimated to be completed in 2020. Onasemnogene abeparvovec has not been evaluated for less severe forms of SMA and long term effects are not known. Onasemnogene abeparvovec has an unspecified PDUFA date in May, 2019.

GenSight announced that in the 72-week, 39 patient, Phase III, RESCUE trial, the eyes treated with birtamimab (GS010) had a loss of visual acuity of 20.6 letters in the ETDRS scale compared to a loss of 21.7 letters in the eyes that received sham injection in patients with LHON who had suffered vision loss of less than 6 months. Vision usually decreases for 3-5 months in LHON before stabilizing. This was seen in the RESCUE trial. Improvement from the nadir to week 48 was 13 letters with birtamimab and 11 letters with sham injection.

Pfizer and Lilly announced that a 16-week, 3,021 patient, Phase III trial, treatment with tanezumab 5mg administered subcutaneously every 8 weeks significantly improved pain and physical function, but not an overall patient assessment compared to naproxen, celecoxib or diclofenac in patients with moderate-to-severe osteoarthritis (OA) of the hip or knee. Tanezumab 2.5mg did not differ from placebo in any of the three primary endpoints. Safety was measured at 80 weeks where treatment with tanezumab 5mg and 2.5mg resulted in a composite of rapidly progressive osteoarthritis (RPOA) type 1 or type 2, subchondral insufficiency fracture, osteonecrosis or pathological fracture in 7.1% and 3.8% of patents compared to 1.5% with naproxen, celecoxib or diclofenac in hip or knee osteoarthritis patients. The incidence of RPOA overall was 6.3% with tanezumab 5mg, 3.2% with 2.5mg arm and 1.2% with the NSAIDs.

Prothera stopped the 260 patient, Phase III VITAL trial early, when an interim analysis found no improvement in a composite endpoint of all-cause mortality or cardiac hospitalizations with birtamimab compared to placebo more than 90-days after the initial infusion in treatment naive patients with AL Amyloidosis and cardiac dysfunction.

New Published Trial Results

Two 48-week, Phase III trials, HAWK with 1,775 patients and HARRIER with 1,049 patients compared brolucizumab to aflibercept. An intravitreal injection of brolucizumab 6mg was given monthly for 3 doses, then every month unless disease activity was present, then the drug was given every two months. Aflibercept 2mg was given as an intravitreal injection every two months. In HAWK, there was also a 3mg brolucizumab group. Brolucizumab was non-inferior to aflibercept in best corrected visual acuity (BCVA) at 48-weeks in both trials. In HAWK, treatment with brolucizumab resulted in an improvement in BCVA of 6.6 letters with 6mg and 6.1 letters with 3mg compared to 6.8 letters with aflibercept. The improvement in BCVA in HARRIER was 6.9 with brolucizumab 6 mg compared to 7.6 with aflibercept. A little more than 50% of patients were maintained on q12w dosing through Week 48 with brolucizumab (56% in HAWK and 51% in HARRIER).

An extension of 251 patients in a Phase II trial found neutralizing antibodies similar for all four serotypes with a booster vaccination given 4-5 years after the 3rd dose of Sanofi’s dengue vaccine. Neutralizing antibodies were superior to levels after the third dose for 3 serotypes.

In the 26-week, 1,758 patients, Phase III Pioneer-3 trial, 63% of patients treated with oral semaglutide 7mg and 14mg lowered HbA1c 0.3 and 0.5% and lowered weight 1.6kg and 2.5kg compared to sitagliptin in patients with type 2 diabetes, inadequately controlled on metformin with or without a sulfonylurea. Semaglutide, 3mg results did not demonstrate non-inferiority to sitagliptin.

In an 8-week, 128 patient, Phase II trial, selopitant reduced itch visual analog scale score by 1 point at 4-weeks and 1.7 points at 8-weeks compared to placebo in patients with prurigo nodularis.

In a 119-patient trial, the addition of apatinib to taxane, irinotecan and fluorouracil resulted in a total remission rate of 15.79% vs 3.23% for the drug regimen without apatinib in patients with patients with gastroesophageal junction adenocarcinoma. Progression-free survival was 3.72 months compared to 3.04 months and overall survival was 13.66 months vs 10.08 months.

In a 2.2-year, 2,648 patient, Phase III trial, 6% of patients treated with atrasentan reached the primary endpoint, a composite of serum creatinine doubling, end-stage kidney disease, chronic dialysis, kidney transplantation, or death from kidney failure compared to 7.9% with placebo in patients with with type 2 diabetes and chronic kidney disease that had responded to atrasentan during an test period before randomization.

The Gap in Oncology Formulary Decision Support Coverage

4/18/2019

 
The American Society of Clinical Oncology (ASCO) lists more than 120 types of cancer and related hereditary syndromes.

Tools are available that provide comparisons of available drug products. Such tools may include a drug’s comparative efficacy, therapeutic role and class monographs to assist with drug therapy decisions once a product is available. Clinicians can access services that detail the information, including access to past reviews, about recently released and investigational drugs projected for approval in the near term.

But how does a formulary management team assess and prepare for perhaps eight new oncology drugs this year? FDA publications? PubMed feeds? Google alerts? Would it help to have a single source of unbiased, comprehensive clinical decision support information in one place?

The Prescribe Right Pharmaceutical Pipeline Tracker contains 157 investigational cancer drugs. There are twenty-one different categories of cancer drugs in our knowledgebase. The ten most common cancers represent 85% of the cancer investigational drug universe: Bladder, Breast Cancer, Colorectal Cancer, Kidney Cancer, Lung Cancer, Lymphoma, Melanoma, Pancreatic Cancer, Prostate Cancer, and Thyroid Cancer.

How does your current process provide coverage of investigational oncology drugs? Do you have a single source that is comprehensive, unbiased, with actionable intelligence? The Pharmaceutical Pipeline Tracker provides concise summaries of clinical trials that not only includes the results, but also the type of patient that was treated and any safety issues that may be present.

Here’s a look at eight oncology drugs that appear to be on the approval near horizon. Comments are taken from the Pharmaceutical Pipeline Tracker knowledgebase:

Quizartinib for acute myeloid leukemia with a PDUFA of May 25, 2019 has Orphan Drug, Breakthrough Therapy and Fast Track Priority Designations. Single-agent quizartinib was shown to be highly active and generally well tolerated in patients with relapsed or refractory acute myeloid leukaemia, particularly those with FLT3-ITD mutations. These findings confirm that targeting the FLT3-ITD driver mutation with a highly potent and selective FLT3 inhibitor is a promising clinical strategy to help improve clinical outcomes in patients with very few options.

Selinexor for multiple myeloma with a July 6, 2019 PDUFA Date has Orphan Drug and Fast Track Priority. The combination of selinexor and dexamethasone has an ORR of 21% in patients with heavily pretreated, refractory myeloma with limited therapeutic options.

Pexidartinib for tenosynovial giant cell tumor with an August 3, 2019 PDUFA Date has Orphan Drug and Breakthrough Therapy Priority Designations. Pexidartinib is also being evaluated for glioblastoma, ovarian, breast, colorectal, pancreatic and prostate cancer, malignant peripheral nerve sheath tumor, and pediatric cancers.

Entrectinib for NTRK‐fusion+ solid tumors with an August 18, 2019 PDUFA Date has Breakthrough Therapy Priority Designation. Roche is seeking approval based on an integrated analysis from four Phase I and II trials that included data from 53 people with ROS1-activating gene fusions and 54 people with locally advanced or metastatic NTRK fusion-positive solid tumors. If approved, entrectinib would compete with larotrectinib to treat NTRK-fusion positive solid tumors and critzotinib to treat ROS1-mutated non-small cell lung cancer.

Polatuzumab for diffuse large B-cell lymphoma with an August 19, 2018 PDUFA Date has Breakthrough Therapy Priority Designation. Current trial data display no significant safety concerns, no independent safety data are yet available. The most common ADR in an 80 patient, Phase II trial were leukopenia, thrombocytopenia and anemia.

Fedratinib (Celgene, Impact Biomedicines) for myelofibrosis with a September 3, 2019 PDUFA Date has no Priority Designations. Sanofi discontinued development of fedratinib in 2013 after the FDA issued a clinical hold due to reports of Wernicke’s encephalopathy in clinical trials. Impact provided safety data to the FDA and the trial resumed. Celgene bought Impact in January 2018.

Erdafitinib for urothelial cancer with a Breakthrough Therapy Priority Designation but no PDUFA date. Janssen submitted an NDA in September 2018. Janssen has the ongoing 630 patient, Phase III THOR trial evaluating erdafitinib compared to chemotherapy or pembrolizumab for the treatment of urothelial carcinoma.

Darolutamide for prostate cancer has no PDUFA Date nor Priority Designations. There are direct links to three published studies in PubMed for Darolutamide in the Pharmaceutical Pipeline Tracker.

Two approvals, an Orphan Drug designation in the week ending April 12

4/15/2019

 
Regulatory Updates

The FDA approved Amgen/UCB’s romosozumab (Evenity)
 on 4/9/2019 for the treatment of osteoporosis in postmenopausal women at high risk for fracture. The drug has a Boxed Warning regarding the increased risk of myocardial infarction, stroke and cardiovascular death. Amgen set WAC for romosozumab at $1,825 a month for an annual cost of $21,900. Romosozumab will likely join abaloparatide and teriparatide as a specialty drug for the treatment of osteoporosis. WAC for abaloparatide is $22,000, while the Federal Supply Schedule price is $11,800. For teriparatide, WAC is $36,000, and the Federal Supply Schedule price is $26,000. ICER estimated the cost per quality adjusted life year gained over the bisphosphonate zoledronic acid as $334,000 for abaloparatide and $942,000 for teriparatide. Due to the delay in FDA review, ICER did not include rombosozumab in its review.

The FDA approved Janssen’s erdafitinib on 4/12/2019 for the treatment locally advanced or metastatic bladder cancer with fibroblast growth factor receptor (FGFR)3 or FGFR2 mutations who have progressed on platinum-containing chemotherapy. A companion lab test was also approved to identify patients with these mutations. WAC for erdafitinib will be $10,080 to $22,680 for a 28-day supply, depending on dose for an annual cost of $131,040 to $294,840.

Celgene and Acceleron submitted a BLA for luspatercept in April 2019.

The FDA designated FibroGen’s pamrevlumab an Orphan Drug for the treatment of Duchenne muscular dystrophy (DMD) in April 2019.

Ghana has accepted 400,000 doses of GSK’s Mosquirix to pilot the malaria vaccine.

Remimazolam is an investigational benzodiazepine whose effects can be reversed with flumazenil. Cosmo Pharmaceuticals licensed US marketing rights for remimazolam from Paion. Cosmo submitted an NDA for remimazolam in April 2019.

New Trial Results Announced

Poxel announced that in a 24-week, 213 patient, Phase III, TIMES 1 trial, imeglimin 1,000 mg lowered HbA1c 0.87% more than placebo. 

New Published Trial Results

The Phase III APECS trial was terminated after an interim analysis showed no improvement with Merck’s verubecestat in the Clinical Dementia Rating Scale-Sum of Boxes compared to placebo in patients with prodromal Alzheimer's Disease. There were 1,454 patients enrolled in the trial at termination and 704 completed the 104-week study period.

In a 12-week, 160 patient, Phase II trial, treatment with Merck’s ruzasvir and uprifosbuvir (no grazoprevir) resulted in SVR in 52/54 genotype 1a patients, 15/15 genotype 1b patients, 28/29 with genotype 2, 30/39 with genotype 3, 18/20 with genotype 4 and 2/3 with genotype 6 in patients chronically infected with HCV genotypes 1-6.

Investigational Update for the Week Ending 6 April 2019

4/9/2019

 
The FDA accepted the NDA for Kyowa Hakko Kirin’s istradefylline in April 2019 and set a PDUFA date of 8/27/2019. Istradefylline is an A2A antagonist seeking approval for the treatment of Parkinson's Disease wearing-off phenomenon in patients on levodopa therapy.
 
The FDA delayed the PDUFA date for Ambit Biosciences Corporation/Daiichi Sankyo’s quizartinib from May to August 2019. This KIT Inhibitor targets acute myeloid leukemia.
 
The FDA granted AstraZeneca’s selumetinib Breakthrough Therapy status. The drug is a MEK Inhibitor targeting differentiated thyroid cancer.
 
The EMA accepted the MAA for Daiichi Sankyo/Plexxikon’s pexidartinib in April 2019. It’s a CSF-1R inhibitor targeting Giant cell tumors of the tendon sheath.
 
Shionogi submitted an MAA for cefiderocol in April 2019.

Immunocore’s IMCgp100 has been assigned the generic name tebentafusp and has both Fast Track and Orphan status. The drug is seeking approval for the treatment of uveal melanoma. It’s an ImmTAC which binds to cancer cells with peptide-HLA. This brings circulating T cells to the tumor site, which releases killing lytic granules, that kill the cancer cell.
 
AZ announced interim results from two cohorts of patients in the Phase Ib, TATTON trial:
  • In a 46 cohort of patients with EGFR-mutant lung cancer with acquired resistance driven by MET amplification after treatment with a first- or second-generation EGFR TKI and negative for T790M mutation treatment with savolitinibin in combination with osimertinib resulted in an objective response rate (ORR) of 52%, with 24 partial responses. 
  • In the second cohort of 48patients with EGFR-mutant lung cancer with acquired resistance driven by MET amplification after treatment with osimertinib or another experimental third-generation EGFR TKI treatment with savolitinibin in combination with osimertinib resulted in an ORR of 28% percent, with 12 partial responses.
 
An analysis of data in two phase 3 trials for Nektar’s NKTR-181, using the MADDERS system, show a low withdrawal rate and a low risk of abuse potential, diversion or addiction.

Syndax announced that an interim analysis from 53 patients with progressing melanoma on prior PD-1 blockade in a cohort of the Phase Ib/II ENCORE 601 trial, treatment with entinostat and pembrolizumab resulted in an objective response in 19% of patients and progression-free survival of 4.2 months.

Allergan announced that in the 123 patient, 28 week, Phase III, open label MAPLE trial, the incidence of intraocular inflammation with a new formulation of abicipar given every two months was 8.9%. The rate of intraocular inflammation in the MAPLE trial was lower than the 15.1 to 15.7% see in the Phase III CEDAR and SEQUOIA trials. The rate of intraocular inflammation is reported as 0.01% with aflibercept, 0 to 0.6% with ranibizumab and 3-55 with brolucizumab. Allergan plans to file a BLA for abicipar in June 2019.

Scynexis’ SCY-078 has been assigned the generic name Ibrexafungerp.

Tonix has an ongoing Phase III trial evaluating cyclobenzaprine for the treatment of fibromyalgia.

Q1 2019 Review – Approvals, Rejections, Delays, Changes in Priority Review Status

4/4/2019

 
Eight Approvals
  • The FDA approved caplacizumab (Cablivi by Sanofi) on 2/6/2019 for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP).
  • The FDA approved triclabendazole (Egaten from Novartis) on 2/13/2019 for the treatment of fascioliasis.
  • The FDA approved turoctocog alfa pegol (Esperoct from Novo Nordisk) on 2/21/2019 for the treatment of hemophilia A, however due to a contractual agreement, the drug will not launch until 2020. Esperocot is a long acting version of NovoEight (turoctocog alfa).
  • On 3/5/2019 the FDA approved esketamine nasal spray, in conjunction with an oral antidepressant, for the treatment of resistant depression. The labeling for esketamine nasal spray contains a Boxed Warning describing a risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors. The drug is only available through a restricted distribution system, under a Risk Evaluation and Mitigation Strategy (REMS). Esketamine must be administered in a certified medical office where the health care provider can monitor the patient for a minimum of 2 hours and determine when the patient can leave. The patient also needs transportation to and from the visit for a dose because they are unable to drive until the day after a dose. Since the patient cannot take the spray home, the treatment sites will need to determine where patients will wait during the monitoring period and coordinate patient visit to avoid a slowdown in office workflow. WAC for esketamine nasal spray is $590 to $885 per treatment session. The drug is dosed twice a week for the initial 4 weeks, so the monthly cost will be $4,720 to $6,785. Esketamine nasal spray is dosed once weekly during the second month ($2,360 to $3,540). In the third month the patient may continue weekly dosing or have their dosing further reduced to every other week, so the WAC price for maintenance dosing is $1,180 to $3,540.
  • The FDA approved netarsudil and latanoprost ophthalmic solution (Rocklatan, Aerie Pharmaceuticals) on 3/13/2019 to decrease elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.
  • The FDA approved solriamfetol (Sunosi, Jazz Pharmaceuticals) on 3/20/2019 to improve wakefulness in adults with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea.
  • The FDA approved brexanolone (Zulresso, Sage Therapeutics) on 3/19/2019 for the treatment of postpartum depression.
  • The FDA approved siponimod (Mayzent, Novartis) on 3/26/2019 to treat adults with relapsing multiple sclerosis. In a draft review ICER felt that compared to best supportive care siponimod reduced the risk of disability progression and decreased inflammation. ICER analysis found that siponimod lowered the risk of relapse by 46% and had an annualized relapse rate of 0.07/year compared to 0.16/year with placebo. See our March 28th special update for more https://www.prescriberight.com/pipeline-news/fda-approves-siponimod-icer-weighs-in-and-april-pdufa-dates
Rejections
  • The FDA rejected Motif Bio’s iclaprim due to concerns over liver toxicity and requested additional liver toxicity data. Iclaprim has Fast Track status and is designated a Qualified Infectious Disease Product by the FDA.
  • The FDA followed an advisory panel recommendation and rejected ALKS 5461 (samidorphan plus buprenorphine) and requested additional efficacy data. Alkermes drug had a PDUFA date of 1/31/2019.
  • The FDA rejected ferric maltol during Shield’s first submission, but the company has resubmitted an NDA, which was accepted by the FDA in December 2018 and assigned a PDUFA date of 7/27/2019. In a 36-week open label extension of the AEGIS-CKD trial, patients originally treated with ferric maltol maintained hemoglobin levels and patients switched from placebo demonstrated a similar rise in hemoglobin. 
  • The FDA rejected sotagliflozin on 3/22/2019. Lexicon and Sanofi are working with the FDA to determine future development of the drug.
Changes in Priority Review Status
  • The FDA designated TG Therapeutics’ umbralisib with breakthrough status for the treatment of marginal zone lymphoma. Umbralisib had previously been designated an orphan drug. 
  • The FDA has granted Daiichi Sankyo/Plexxikon’s pexidartinib breakthrough therapy and orphan drug designations and set a PDUFA date of 8/3/2019.
  • The FDA designated AT-GAA as a Breakthrough Therapy in February 2019.
  • The FDA has granted fedratinib a priority review, with a PDUFA date of 9/3/2019. There are now twenty-five investigational drugs with PDUFA Dates between March 14, 2019 and December 25, 2019
  • The FDA removed the Breakthrough Therapy designation for oliceridine because current data did not support the designation. The FDA does feel the current safety data will support a refiled NDA after Trevena completes a Phase I safety study examining QT-interval prolongation.
  • The FDA granted Orphan Drug status to Armetheon’s tecarfarin for the prevention of systemic thromboembolism of cardiac origin in patients with End Stage Renal Disease (ESRD) and Atrial Fibrillation (AFib).
  • The FDA granted Qualified Infectious Disease Product (QIDP) to the oral and IV formulations of sulopenem in March 2019.  
Holds and Delays
  • The FDA has put a partial hold on an axalimogene filolisbac Phase III cervical cancer trial, until Advaxis provides additional chemistry, manufacturing and controls information. Under the hold, no new patients can be enrolled in the trial, but current patients can continue to be treated.
  • On 2/28/2019, the FDA Oncologic Drugs Advisory Committee recommend a delay in approval of selinexor-dexamethasone to treat triple class-refractory myeloma until after the results of the Phase III BOSTON trial are available in the first half of 2020. An FDA review of selinexor found limited efficacy and significant toxicity in patients with relapsed/refractory multiple myeloma treated with a combination of selinexor dexamethasone. Based on data submitted and historical studies with high-dose dexamethasone, the FDA felt it was difficult to isolate the treatment effect of selinexor. 
  • The FDA delayed a decision on NKTR-181 by three months to allow additional time to review preclinical data from two additional studies and set a new PDUFA date of 8/29/2019.
  • In March 2019, the FDA delayed the PDUFA date for Karyopharm Therapeutics’ selinexor by three months (from April 6, 2019 to July 6, 2019).
New NDAs and BLAs
  • The FDA accepted an NDA for diroximel fumarate on 2/25/2019 suggesting a PDUFA date of 12/25/2019.
  • The FDA has accepted the BLA for entrectinib, which suggests a PDUFA date of August 18, 2019.
  • The FDA has accepted the BLA for polatuzumab, which suggests a PDUFA date of August 19, 2019.
  • The FDA has accepted the NDA for upadacitinib, which suggests a PDUFA date of August 19, 2019.
  • The FDA has accepted the NDA for oral and IV lefamulin, which suggests a PDUFA date of August 19, 2019.
  • The FDA accepted the NDA for Bioproject Pharma’s pitolisant on 2/12/2019, which suggests a PDUFA date of 8/12/2019. Pitolisant has both Fast Track and Breakthrough Therapy status.
  • The FDA accepted the NDA for Sarepta Therapeutics’ golodirsen on 2/14/2019 and set a PDUFA date of 8/19/2019.
  • The FDA accepted the NDA for ubrogepant on 3/11/2019. Allergan expects a 4Q19 PDUFA date of 12/27/19
  •  The FDA accepted the NDA for lemborexant on 3/11/2019. Allergan expects a 4Q19 PDUFA date of 12/27/19

Investigational Update for the Week Ending March 29

4/1/2019

 
Regulatory Updates
  • In January 2019, the FDA delayed the PDUFA date for bremelanotide and set a new date of 6/23/2019. 
  • The FDA granted recombinant human pentraxin 2 breakthrough therapy status.
  • Celgene resubmitted an NDA for ozanimod in March 2019. 
  • Santhera filed an MAA for idebenone in March 2019.
  • SRP-4045 has been assigned the generic name of casimersen.
  • Bluebird changed the brand name for beta beglogene darolentivec to Zynteglo. Previously it was called LentiGlobin. CHMP recommend approval of beta beglogene darolentivec in March 2019.
Newly Published Trial Results
  1. In a 133 patient, Phase III trial, patients treated with anlotinib had a similar PFS compared to sunitinib (17.5 vs. 16.6 months) as initial treatment in patients with metastatic renal cell carcinoma. 
  2. In a 14-week, 671 patient, Phase III trial, mirogabalin 15, 20, or 30 mg/day decreased the average daily pain score -0.41, -0.47, and -0.77 compared to placebo in patients with postherpetic neuralgia.
  3. In a 24-week, 216 patient, Phase III, open label trial, daprodustat increased hemoglobin by 0.69 g/dL after 4 weeks and maintained the level at 24 weeks in hemodialysis patients with anemia switched from a stable dose of epoetin to daprodustat. In a 24-week, 252 patient, Phase III, open label trial, daprodustat maintained hemoglobin at 24 weeks in chronic kidney disease patients with anemia switched from a stable dose of epoetin to daprodustat.
  4. In a 52-week, 166 patient, open label, extension trial, treatment with pemafibrate resulted in a 42.3 to 48.2% decrease in triglycerides in patients with hypertriglyceridemia and Type 2 diabetes.
  5. In an 8-week, 222 patient, dose-ranging trial, viloxazine improved the ADHD Rating Scale (RS)-IV total score for 200, 300 and 400 mg compared to placebo in children aged 6 to 12 years of age with attention deficit hyperactivity disorder.
  6. In a 122 patient, Phase II trial, 54% of patients treated with polatuzumab vedotin/rituximab (n=39) had an objective response and 21% had a complete response, compared to an objective response in 60% of patients and a complete response in 26% of patients treated with pinatuzumab vedotin/rituximab (n=42) in patients with diffuse large B-cell lymphoma. In the same trial 70% of patients treated with polatuzumab vedotin/rituximab (n=20) had an objective response and 45% had a complete response, compared to an objective response in 62% of patients and a complete response in 5% of patients treated with pinatuzumab vedotin/rituximab (n=21) in patients with follicular lymphoma.
New Trial Results Announced
  1. Aldeyra announced that 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.
  2. Novartis treated 137 patients with open label osilodrostat for 24 weeks. Patients that had been on a stable dose since week 12 and had a UFC in normal range were randomized to osilodrostat or placebo for 8 weeks. In the 70 patients that were included in the Phase III trial, 86% of patients treated with osilodrostat had a UFC in the normal range compared to 29% of those switched to placebo in patients with Cushing's disease. Current trial data display no significant safety concerns; no independent safety data are yet available. In a 137 patient Phase III trial, the most common ADR with osilodrostat were nausea, headache, fatigue and adrenal insufficiency. Almost 11% discontinued treatment due to ADRs.  
  3. Aimmune announced that in the 9-month, 175 patient, Phase III ARTEMIS trial, treatment with AR101 resulted in a median tolerated dose of peanut protein of 1000mg in pediatric patients with peanut allergy. 
  4. Proteon announced that in the 12-month, 603 patient, Phase III, PATENCY 2 trial, treatment with vonapanitase did not reduce fistula use for hemodialysis or secondary patency compared to placebo in hemodialysis patients with a new radiocephalic fistula.
  5. Sarepta announced interim results at 48-weeks from the 96-week, 43 patient, Phase III, ESSENCE trial, where casimersen increased mean dystrophin protein levels compared to placebo in patients with Duchenne Muscular Dystrophy amenable to skipping exons 45. Sarepta plans to submit an NDA in mid-2019.
  6. Astellas and Seattle Genetics announced interim results from a 128 patient cohort enrolled in a Phase II, open label trial, where treatment with enfortumab vedotin resulted in a 44% objective response rate in patients with locally advanced or metastatic urothelial cancer who progressed after receiving platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor.
  7. Gilead and Galapagos announced interim 24-week data from the 52-week, 1,759 patient, Phase III, FINCH 1 trial, in which filgotinib was superior to placebo in achieving ACR20/50/70 with filgotinib 200 mg (76.6%, 47.2%, 26.3%), filgotinib 100 mg (69.8%, 36.3%, 18.5%) compared to adalimumab (70.8%, 35.1%, 14.2%) and placebo (49.9%, 19.8%, 6.7%) in patients with moderate-to-severe rheumatoid arthritis with an inadequate response to methotrexate (MTX). Gilead and Galapagos announced interim data from the 24-week, 1,252 patient, Phase III, FINCH 3 trial, where filgotinib/MTX was superior to MTX monotherapy in achieving ACR20/50/70 with filgotinib 200 mg/MTX (81%, 61.5%, 43.8%), filgotinib 100 mg/MTX (80.2%, 57%, 40.1%) compared to filgotinib 200 mg (78.1%, 58.1%, 40%) and methotrexate (71.4%, 45.7%, 26%) in patients with with moderate-to-severe rheumatoid arthritis naive to methotrexate.
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