Key Drug Launches To Plan For In 2019
Executive Summary
Around three dozen key late-stage products could reach their first markets in 2019, according to a recent report from Informa Pharma's Biomedtracker. Company execs may need to plan for the disruptive potential of this group of new medicines on established markets and standards of care.
As a supplement to its quarterly Outlook reports, Informa Pharma's Biomedtracker has taken a longer-term look at some key late-stage drugs projected to enter their first markets in 2019. These drugs represent new drug classes, major changes to standards of care, and large market opportunities, say Biomedtracker analysts in a new report, Key Potential Drug Launches In 2019.
Drugs that could be launched during 2019 could include Novartis AG's brolucizumab as a long-acting anti-VEGF therapy for wet age-related macular degeneration, Johnson & Johnson's esketamine for treatment-resistant depression, and potentially the third CAR-T therapy to reach the market, Celgene Corp.'s lisocabtagene maraleucel (liso-cel) for the treatment of B-cell lymphomas.
If launched, the 2019 products could provide new therapeutic options for patients with acute hepatic porphyria attacks, sickle cell anemia, bacterial pneumonia, acute myeloid leukemia, and multiple myeloma. Some of the more important expected products are:
Novartis's Brolucizumab For Wet Age-Related Macular Degeneration
Novartis's brolucizumab has the potential to extend the dosing intervals for intravitreal anti-VEGF therapy to once every 12 weeks in the treatment of neovascular retinal disorders, the report says. The pivotal HAWK and Harrier clinical trials in wet age-related macular degeneration, which include Bayer AG's Eylea (aflibercept) as the comparator, met their primary non-inferiority endpoints, with the majority of patients being able to maintain quarterly dosing.
The full dataset is expected to be presented at the American Academy of Ophthalmology (AAO) meeting in October 2018, where there will be much scrutiny of efficacy versus administration frequency. A regulatory filing is expected in December 2018, and brolucizumab could become commercially available before the end of 2019. (Also see "Novartis Back In AMD Game With ‘Potential Blockbuster’ Brolucizumab" - Scrip, 12 Nov, 2017.)
Johnson & Johnson's Esketamine For Depression
Johnson & Johnson is developing the S-enantiomer of ketamine for intranasal administration, as esketamine, for the treatment-resistant depression, building on growing evidence of ketamine's potent and rapid antidepressant effect. The company is nearing the end of a large-scale Phase III program, with regulatory filings expected in the second half of 2018.
In Phase II studies, esketamine showed a large nine-point treatment effect on the Montgomery-Asberg Depression rating scale (MADRS), surpassing any other antidepressant. However, there were mixed top-line data from the two Phase III studies, TRANSFORM-2 in adults aged up to 64 years, and in TRANSFORM-3 in the elderly. Several side effects have emerged with esketamine including dissociative symptoms, which are seen predominantly on the day of dosing, and were generally transient and resolved on the day of dosing. Ketamine, used recreationally at high doses, can result in hallucinogenic side effects, which have led to ketamine being a drug of abuse. Sales of $2.5bn could be achieved by 2024, estimate the Biomedtracker analysts. (Also see "J&J's Mixed Phase III Data For Esketamine Highlight Challenges In Resistant Depression" - Scrip, 7 May, 2018.)
Celgene's Lioscabtagene Maraleucel For DLBCL
The Phase I study, TRANSCEND, of Celgene's CAR-T therapy, lisocabtagene maraleucel (liso-cel) has shown strong efficacy at three and six months (CR rates of 51% of 46%, respectively), and may have an improved safety profile compared with other CAR-T therapies, including a lower rate of cytokine release syndrome.
Like Gilead Sciences Inc.'s Yescarta and Novartis' Kymriah, liso-cel targets the CD19 antigen, but a key point of differentiation for liso-cel is that the patient's CD4 and CD8 cells are separated before transduction with the chimeric antigen receptor. The independently transduced cells are then administered to the patients in a defined ratio.
Celgene expects to file a US BLA for liso-cel in relapsed/refractory diffuse large B-cell lymphoma in the second of 2018, with a possible market launch in 2019. (Also see "Celgene Maintains Otezla Confidence, But Is Reconsidering IBD Indications" - Scrip, 26 Jul, 2018.)
Nabriva's Lefamulin In CABP
Nabriva Therapeutics PLC's lefamulin is a potent antibacterial with favorable pharmacokinetics and is being evaluated in oral and intravenous formulations for community-acquired bacterial pneumonia (CABP). Marketing applications are expected to be submitted in the second half of 2018 as a first-line treatment of hospitalized patients with CABP, and as an alternative to fluoroquinolones. Only one other pleuromutilin, retapumilin, is currently approved for therapeutic use. (Also see "Nabriva Gains New CEO And Near-Market Antibiotic, Claims Leadership Role" - Scrip, 25 Jul, 2018.)
Ardelyx's Tenapanor For Irritable Bowel Syndrome With Constipation
Ardelyx Inc.'s tenapanor is a first-in-class NH3E inhibitor being evaluated for two indications, irritable bowel syndrome with constipation (IBS-C), and hyperphosphatemia. IBS-C is the most advanced indication with positive results in two Phase III trials comparing tenapanor to placebo.
Tenapanor results compare well to historical Phase III data for Ironwood Pharmaceuticals Inc./Allergan PLC's Linzess (linaclotide) and Synergy Pharmaceuticals Inc.'s Trulance (plecantide), but the real differentiator is the novel mode of action of tenapanor. Ardelyx expects to submit a US NDA in the second half of 2018, setting the product up for an approval in 2019. (Also see "Ardelyx Outlines Next Phase III Steps For Tenapanor, Ditches RDX7675" - Scrip, 21 Nov, 2017.)
Alnylam's Givosiran In Porphyria
Current options for acute hepatic porphyria attacks are limited, and Alnylam Holding Co.'s givosiran could be an important addition for the prevention and possibly treatment of such attacks. Givosiran is a subcutaneous RNAi therapeutic which targets aminolevulinate synthase and has orphan and breakthrough designations.
In a Phase I study, givosiran dramatically lowered the rate of attacks and the need for hemin, and the results of a Phase III study are expected in 2018 and could precede a year-end 2018 NDA filing. (Also see "Alnylam's Overshadowed Givosiran Comes Into The Phase III Light" - Scrip, 28 Jun, 2017.)
Acceleron's Luspatercept In MDS And Beta-Thalassemia
Acceleron Pharma Inc.'s luspatercept is the most advanced TGF-beta inhibitor in development for myelodysplastic syndromes (MDS) and beta-thalassemia, and would represent a new drug class for both indications.
In Phase II studies, luspatercept was well tolerated and showed strong and sustained increases in hemoglobin and decreases in transfusion burden. Top-line results from the Phase III MEDALIST study in MDS and the BELIEVE study in anemia due to beta-thalassemia are expected in mid-2018, positioning luspatercept for approvals in 2019. (Also see "Attention Turns To Celgene's Other Pipeline Prospects Following Second Positive Luspatercept Read-Out" - Scrip, 10 Jul, 2018.)
Pfizer's Glasdegib For AML
Pfizer Inc.'s glasdegib is the first hedgehog pathway inhibitor to be developed for the treatment of acute myeloid leukemia (AML), and so far has shown improved overall survival in a Phase II trial in higher-risk AML patients who are ineligible for high-intensity induction chemotherapy. The Phase III BRIGHT AML1019 trial suggests that it will be further developed as a first-line therapy regardless of whether patients can tolerate high-intensity induction chemotherapy. The US FDA has accepted an NDA for glasdegib under priority review, with a PDUFA date in December 2018. (Also see "Pfizer's Three-Pronged Oncology Strategy Includes Expanding Ibrance, Xtandi, Developing Blockbuster Combos " - Scrip, 22 May, 2018.)
Ablynx's Caplacizumab For TTP
Ablynx NV's Nanobody, caplacizumab, could become the first drug specifically approved for acquired thrombotic thrombocytopenic purpura (TTP), with approval in Europe expected this year and US approval possibly not until 2019.
In a Phase III study, caplacizumab met its primary endpoint of platelet count response, and markedly reduced the rate of recurrences of TTP episodes, although it has increased bleeding adverse events. The drug is awaiting approval in Europe, but approval in the US may not come until 2019.
Alexion's ALXN1210 For PNH
A long-acting C5 complement inhibitor, Alexion Pharmaceuticals Inc.'s ALXN1210, can be administered every eight weeks, and has been found to be non-inferior to Alexion's blockbuster therapy, Soliris (eculizumab), for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
A PDUFA decision is expected in Feb. 2019, and could help fend off competition from eclizumab biosimilars, which are expected to enter the market in 2021, as well as other potential competitors which are in development.
ALXN1210 has shown non-inferiority to Soliris in two pivotal studies while also demonstrating numerical improvements.
Karyopharm's Selinexor In Multiple Myeloma
Karyopharm Therapeutics Inc.'s selinexor is a first-in-class inhibitor of the nuclear export protein, XPO1. When XPO1 is inhibited, tumor suppressor proteins accumulate in the cell nucleus, leading to the selective induction of apoptosis in cancer cancers.
Karyopharm intends to submit a US NDA to the FDA in the second half of 2018, with a request for accelerated approval for oral selinexor as a new treatment for patients with penta-refractory multiple myeloma. An EU submission is expected in early 2019, with a request for a conditional approval. (Also see "New Mechanism And Oral Activity Underline Selinexor's Role In Multiple Myeloma " - Scrip, 1 May, 2018.)
Foamix's FMX101 For Acne
Foamix Pharmaceuticals Ltd.'s FMX101 could become the first topical minocycline product to be approved for acne. Top-line results from a third pivotal trial are expected in the third quarter of 2018, and if successful, will be used to support regulatory marketing submissions to the US FDA before year-end 2018.
FMX1010 is a long-acting tetracycline with a broad spectrum of antibacterial activity as well as anti-inflammatory properties.
Further details of the Biomedtracker report, Key Potential Drug Launches in 2019, are available here.