In 2026, the global pharma and biotech industry is heading into another surge of innovation. On the FDA's watchlist, several late-stage therapies aimed at major unmet needs—from metabolic and neurological diseases to cancer and cardiovascular conditions—are nearing potential approval.
These drugs go beyond incremental updates. They include dual-pathway obesity treatments, neurological therapies designed to address disease at its root, and one-time gene therapies that could change the course of rare diseases. If approved, they may improve the lives of millions of patients and reshape competition in multibillion-dollar markets.
This article looks at the FDA drug approvals most worth watching in 2026.
Metabolic Disease & Obesity: Dual Targets and Oral Options Set the Pace
Obesity and related metabolic disorders remain one of the world’s biggest public health challenges. In 2026, FDA decisions are expected to highlight two major shifts in treatment: dual-target “GLP-1+” therapies and more patient-friendly formulations, both aimed at better results and long-term adherence.
Novo Nordisk's CagriSema: Fixed-dose Injectable Combination
CagriSema is a once-weekly fixed-dose injectable medicine that combines two complementary pathways: the GLP-1 receptor agonist semaglutide and the long-acting amylin analogue cagrilintide. If approved, CagriSema would become the first injectable GLP-1 receptor agonist and amylin analogue fixed-dose injectable combination treatment.
In December 2025, Novo Nordisk submitted its New Drug Application (NDA) to the FDA for once-weekly CagriSema (cagrilintide 2.4mg and semaglutide 2.4mg) injection for chronic weight management in adults with obesity or overweight plus at least one weight-related condition. The FDA is expected to complete its review in 2026.
The application is supported by the Phase 3 REDEFINE 1 and REDEFINE 2 trials. In REDEFINE 1, which enrolled over 3,400 adults without diabetes, patients treated with CagriSema achieved an average weight loss of 20.4% at 68 weeks, compared with 3.0% for placebo. When assuming all patients stayed on treatment, weight loss reached 22.7% in CagriSema group versus 2.3% in the placebo group. 91.9% of participants taking CagriSema lost at least 5% of their body weight compared to 31.5% for the placebo group. [1]
Eli Lilly's Orforglipron: Oral GLP-1 Agonist
Orforglipron is Eli Lilly’s oral, small-molecule GLP-1 receptor agonist—and the first non-peptide GLP-1 to advance into Phase 3 trials. Unlike injectable GLP-1 therapies, it is taken once daily as a pill, with no restrictions on food or water, offering a far more convenient option for long-term treatment.
Designed for both obesity and type 2 diabetes, orforglipron targets a broad metabolic population and addresses one of the biggest barriers to GLP-1 use: injections.
Eli Lilly reported positive topline results from the Phase 3 ATTAIN-MAINTAIN trial, evaluating orforglipron, a once-daily oral, non-peptide GLP-1 receptor agonist, for long-term weight maintenance. [2]
The study enrolled participants from SURMOUNT-5 who had already completed 72 weeks of treatment with the highest tolerated doses of Wegovy (semaglutide) or Zepbound (tirzepatide) and had reached a weight-loss plateau. These patients were re-randomized to receive orforglipron or placebo for an additional 52 weeks, alongside diet and physical activity.
At 52 weeks, orforglipron met the primary and all key secondary endpoints, showing significantly better maintenance of weight loss compared with placebo.
◆ Participants switching from Wegovy to orforglipron maintained their prior weight loss with an average difference of 0.9 kg, while those switching from Zepbound maintained weight loss with an average difference of 5.0 kg (efficacy estimand).
In post-hoc analyses at 24 weeks, clear separation from placebo was already evident:
◆ Patients switching from Wegovy showed a –0.1 kg change in body weight versus a 9.4 kg gain in the placebo group.
◆ Patients switching from Zepbound had a 2.6 kg change versus 9.1 kg with placebo.
Lilly has submitted an NDA to the FDA for orforglipron in adults with obesity or overweight, and the drug has received a Commissioner’s National Priority Voucher. The bank forecasts oral GLP-1s will capture about $22 billion, or 24% of the global weight-loss market, by 2030. Of that, Lilly’s orforglipron is expected to take 60% ($13.6B) versus just 21% ($4B) for Novo's Wegovy pill. [3]
Oncology: Gedatolisib Sets a New Bar in HR+/HER2− Breast Cancer
Gedatolisib, developed by Celcuity, is a next-generation pan-PI3K/mTOR inhibitor being evaluated for HR-positive, HER2-negative advanced breast cancer, with additional studies underway in metastatic castration-resistant prostate cancer. The drug is given as a once-weekly intravenous infusion for three weeks in a 28-day cycle.
Unlike single-target PI3K or mTOR inhibitors, gedatolisib is designed to block the pathway more completely. It simultaneously inhibits all four class I PI3K isoforms (α, β, γ, δ) as well as mTORC1 and mTORC2, helping to shut down key escape routes in the PI3K/mTOR pathway and delay treatment resistance.
In November 2025, Celcuity completed its NDA submission to the U.S. FDA for gedatolisib in PIK3CA wild-type HR+/HER2− advanced breast cancer, based on results from the Phase 3 VIKTORIA-1 trial.[4]
The data showed striking clinical benefit. In the gedatolisib triplet (gedatolisib + fulvestrant + palbociclib), the risk of disease progression or death was reduced by 76% compared with fulvestrant alone (HR 0.24). Median progression-free survival reached 9.3 months, versus 2.0 months with fulvestrant—an improvement of 7.3 months.
The gedatolisib doublet (gedatolisib + fulvestrant) also delivered strong results, reducing progression or death by 67% (HR 0.33) and extending median PFS to 7.4 months, compared with 2.0 months for fulvestrant alone.
Together, these results position gedatolisib as a potential new backbone therapy for HR+/HER2− advanced breast cancer, especially in patients with PIK3CA wild-type disease, where treatment options remain limited.
Cardiovascular: Enlicitide Brings PCSK9 Inhibition to a Daily Pill
PCSK9 inhibitors are among the most effective therapies for lowering LDL cholesterol, but today’s options are all injectables. As a result, real-world use remains below 5%, largely due to poor patient adherence. Merck’s enlicitide aims to change that by becoming the first oral PCSK9 inhibitor, offering powerful LDL lowering in a simple daily pill.
Enlicitide is a novel small-molecule macrocyclic peptide that blocks the interaction between PCSK9 and the LDL receptor, using the same biological pathway as injectable monoclonal antibodies—without the needle. By preserving LDL receptors on the cell surface, it increases the clearance of LDL cholesterol from the bloodstream.
In November 2025, results from the pivotal Phase 3 CORALreef Lipids trial were presented for the first time. At 24 weeks, once-daily enlicitide decanoate reduced LDL-C by 55.8% versus placebo in the primary analysis (p < 0.001). A post-hoc reanalysis showed an even greater reduction of 59.7% (p < 0.001), confirming both statistical and clinical significance. [5]
With oral dosing and LDL-lowering efficacy comparable to injectable PCSK9 therapies, enlicitide has the potential to become the first FDA-approved oral PCSK9 inhibitor—and to dramatically expand access to this proven cholesterol-lowering mechanism.
Neurology: Oveporexton Redefines Narcolepsy Type 1 Treatment
Narcolepsy type 1 (NT1) is caused by the loss of orexin-producing neurons in the hypothalamus, leading to chronic orexin deficiency. Current treatments can reduce sleepiness or cataplexy, but they do not address the root cause of the disease.
Oveporexton (TAK-861) is the first selective orexin receptor 2 (OX2R) agonist designed to restore orexin signalling itself. By directly activating OX2R, the drug aims to normalise the sleep–wake cycle, improve daytime alertness, and reduce abnormal REM-sleep events such as cataplexy.
In September 2025, Takeda presented data from two global Phase 3, FirstLight (TAK-861-3001) and RadiantLight (TAK-861-3002). Both studies met all primary and secondary endpoints demonstrating statistically significant improvement across a broad range of NT1 symptoms compared to placebo with p-values of <0.001 across all doses (twice-daily 1mg/twice-daily 2mg) at week 12. Treatment led to better wakefulness, with longer sleep latency on objective tests and lower daytime sleepiness scores reported by patients. Weekly cataplexy episodes dropped sharply, with a median reduction of more than 80%. Patients also reported milder overall disease severity and clear improvements in daily functioning and quality of life. [6]
Takeda plans to submit an NDA by March 2026. If approved, oveporexton would become the first therapy to directly target the cause of NT1—filling a 20-year gap in treatment innovation.
Autoimmune Disease: Icotrokinra Brings IL-23 Blockade to an Oral Pill
Icotrokinra is emerging as a potential first-in-class oral peptide therapy for autoimmune diseases. By selectively blocking the IL-23 receptor, it directly shuts down the IL-23/Th17 inflammatory pathway—a key driver of diseases such as moderate-to-severe plaque psoriasis and ulcerative colitis.
Developed jointly by Johnson & Johnson and Protagonist Therapeutics, icotrokinra (JNJ-77242113 / JNJ-2113) is the first cyclic peptide designed to target the IL-23 receptor. Unlike approved IL-23 biologics, which require injections, icotrokinra is taken once daily as an oral pill, offering a more convenient and patient-friendly option. In July, Johnson & Johnson submitted an NDA to the U.S. FDA for the treatment of plaque psoriasis.
The NDA is supported by four pivotal Phase 3 studies from the ICONIC program—ICONIC-LEAD, ICONIC-TOTAL, and ICONIC-ADVANCE 1 and 2. Across adults and adolescents aged 12 and older with moderate-to-severe plaque psoriasis, icotrokinra met all primary and co-primary endpoints. At week 16, significantly more patients achieved clear or almost clear skin (IGA 0/1) and PASI 90 compared with placebo, with a favorable safety profile.
With strong efficacy, high selectivity, and simple oral dosing, icotrokinra has the potential to redefine IL-23–targeted therapy and open a new chapter in the treatment of autoimmune diseases.
Rare Disease: Zilganersen Brings Disease-Modifying Therapy to Alexander Disease
Alexander disease (AxD) is a rare, progressive, and often fatal genetic neurological disorder caused by mutations in the GFAP gene, leading to toxic protein buildup and white-matter damage. There are currently no approved treatments.
Zilganersen, developed by Ionis, is an investigational antisense oligonucleotide designed to reduce excess GFAP at its source. By lowering the production of the toxic protein, it aims to slow—or stabilize—disease progression rather than simply manage symptoms.
In a pivotal study with results released in September 2025, patients treated with zilganersen 50 mg demonstrated statistically significant and clinically meaningful stabilization on the primary endpoint of gait speed as assessed by the 10-Meter Walk Test (10MWT) compared to control at week 61 (mean difference 33.3%, p=0.0412) with favorable safety and tolerability. Zilganersen also demonstrated consistent benefit in key secondary endpoints. These data mark the first time an investigational medicine has shown a positive disease-modifying impact in AxD. [8]
Zilganersen has received Breakthrough Therapy, Orphan Drug, and Rare Pediatric Disease designations from the FDA, as well as Orphan Drug status from the EMA. Ionis plans to submit an NDA to the FDA in Q1 2026 and is preparing to launch an Expanded Access Program in the U.S.
References:
[1]https://www.prnewswire.com/news-releases/novo-nordisk-files-for-fda-approval-of-cagrisema-the-first-once-weekly-combination-of-glp1-and-amylin-analogues-for-weight-management-302645862.html
[2]https://investor.lilly.com/news-releases/news-release-details/lillys-orforglipron-helped-people-maintain-weight-loss-after
[3]https://www.drugdiscoverytrends.com/novo-nordisk-launches-first-glp-1-pill-for-obesity-but-lilly-may-dominate-the-oral-market-eventually/
[4]https://ir.celcuity.com/news-releases/news-release-details/celcuity-announces-completion-submission-its-new-drug
[5]https://www.merck.com/news/mercks-enlicitide-decanoate-an-investigational-oral-pcsk9-inhibitor-significantly-reduced-ldl-c-in-phase-3-coralreef-lipids-trial/
[6]https://www.takeda.com/newsroom/newsreleases/2025/takeda-orexin-data-oveporexton-phase-3-narcolepsy-world-sleep-2025/
[7]https://www.jnj.com/media-center/press-releases/johnson-johnson-seeks-first-icotrokinra-u-s-fda-approval-aiming-to-revolutionize-treatment-paradigm-for-adults-and-adolescents-with-plaque-psoriasis
[8]https://ir.ionis.com/news-releases/news-release-details/ionis-receives-us-fda-breakthrough-therapy-designation
[9]https://www.prnewswire.com/news-releases/clarivate-identifies-eleven-potential-blockbuster-and-transformative-therapies-in-its-2026-drugs-to-watch-report-302653631.html
