Traditional Drug Pipeline Monthly Update: October 2023

This monthly pipeline wrap-up provides a review of newly approved drugs, recent drug launches, generic updates, new indications and news of note on drugs in the approval process.

See separate article for pipeline information on specialty drugs.

New Drug Information

• Xphozah® (tenapanor): The FDA approved Ardelyx’ sodium hydrogen exchanger 3 (NHE3) inhibitor Xphozah to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy.[1] The recommended dosage is 30 mg orally twice daily before the first and last meals of the day. The dosage may be adjusted based on serum phosphorus levels and gastrointestinal tolerability. Tenapanor is the first phosphate absorption inhibitor that acts locally in the gut to inhibit NHE3. Across three Phase 3 clinical trials (BLOCK [NCT02675998], PHREEDOM [NCT03427125]), and AMPLIFY [NCT03824587]), the serum phosphorus concentration was 0.7 mg/dL lower in patients treated with Xphozah compared to those who received placebo.[2]^,[3],[4] Xphozah is anticipated to be available in the U.S. in November 2023.
• Qlosi™ (pilocarpine 0.4% ophthalmic solution): The FDA approved a new formulation of pilocarpine, Qlosi, for the treatment of presbyopia in adults.[5] The recommended dosage is 1 drop instilled in each eye. The dose can be repeated a second time after 2 to 3 hours for an effect lasting up to 8 hours. The cholinergic agent may be administered on a daily basis, or as needed, up to twice each day. Two Phase 3 trials, NEAR-1 (NCT04599933) and NEAR-2 (NCT04599972), demonstrated that 2 doses of Qlosi resulted in a gain from baseline of ≥ 3 lines in near binocular distance-corrected visual acuity (BDCVA) at 40 cm without a loss of ≥ 1 lines (≥ 5 letters) in BDCVA at 4 meters. Qlosi is the second ophthalmic solution FDA approved for presbyopia, following the October 2021 approval of Vuity® (pilocarpine 1.25% ophthalmic solution) that is administered once daily. Oasis is planning a 2024 launch of Qlosi.
• Combogesic IV (acetaminophen and ibuprofen): Combogesic IV, by Hikma/Hyloris Pharmaceuticals, was approved under the FDA’s 505(b)(2) pathway to provide short-term pain relief. It is indicated for use in adults where an intravenous (IV) route of administration is considered clinically necessary for: (1) the relief of mild to moderate pain, or (2) the management of moderate to severe pain as an adjunct to opioid analgesics.[6] In a Phase 3 clinical trial, Combogesic IV provided more effective pain relief compared to placebo, acetaminophen alone, or ibuprofen alone, as demonstrated by the sum of pain intensity differences over 48 hours after bunionectomy surgery. Combogesic IV is anticipated to be available in the U.S. in 2024.
• Cabtreo™ (clindamycin phosphate, adapalene, benzoyl peroxide): FDA approved the first triple-combination topical treatment for acne vulgaris, which contains an antibiotic, a retinoid and a antibacterial agent. Cabtreo is a topical gel comprised of clindamycin 1.2%,  adapalene 0.15%, and benzoyl peroxide 3.1%.[7] It is applied to affected skin once daily. Efficacy of Cabtreo was evaluated in two phase 3 clinical trials, Study 1 (NCT04214639) and Study 2 (NCT04214652). In both trials, a greater proportion of patients treated with Cabtreo achieved clear or almost clear skin compared to those who received vehicle (Study 1, 49.6% versus 24.9%, respectively; Study 2, 50.5% versus 20.5%, respectively). Cabtreo is not approved for use in patients < 12 years of age. Bausch Health aims for commercial availability of Cabtreo in Q1 2024.
• Likmez™ (metronidazole): The FDA has approved Likmez under their 505(b(2) pathway. Likmez is a nitroimidazole antimicrobial indicated to treat trichomoniasis in adults, anaerobic bacterial infections in adults, and amebiasis in adults and pediatric patients.[8] It is the only ready-to-use metronidazole oral suspension. It is approved as a 500 mg/5 mL concentration that does not require refrigeration. The recommended dosage is dependent on the indication, and patient age and/or body weight.

Exxua™ (gepirone): The antidepressant Exxua, by Fabre-Kramer, has been approved to treat major depressive disorder (MDD) in adults.[9] Exxua is the first selective serotonin 1A (5-HT1A) receptor agonist for MDD. It is approved as extended-release tablets in 4 strengths with a recommended starting dose of 18.2 mg orally once daily, that may be titrated to a maximum dose of 72.6 mg (36.3 mg in elderly). Electrolyte abnormalities and electrocardiogram (ECG) must be performed prior to initiating therapy and ECG should be repeated during dose titration and periodically. Similar to other antidepressants, Exxua labeling has a boxed warning for suicidal thoughts and behaviors. In two phase 3 trials, Exxua demonstrated statistically significant improvement over placebo in depressive symptoms, as measured by the Hamilton Depression Rating Scale (HAMD-17) total score at week 8 (placebo-adjusted, -2.47 and -2.45). A first half 2024 launch is anticipated with pricing to follow.

• Ryzumvi™ (phentolamine 0.75% ophthalmic solution): The FDA approved Ryzumvi, an alpha adrenergic blocker, under their 505(b)(2) pathway. It is indicated for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) agents. Safety and efficacy have been established in patients 3 years and older. Ryzumvi is instilled in each dilated eye to reverse mydriasis following the completion of the ophthalmic examination or procedure. Pharmacologically induced mydriasis can last up to 24 hours. In the phase 3 MIRA-2 and MIRA-3 trials, Ryzumvi was administered one hour after instillation of a mydriatic agent. The studies showed that at all time points measured from 60 minutes through 24 hours, a significantly greater percentage of patients treated with Ryzumvi experienced the return of pupil diameter to ≤ 0.2 mm from baseline diameter compared to patients who received placebo (placebo-adjusted difference ranged from 25% at 60 minutes to 91% at 24 hours). Ocuphire is expected to launch Ryzumvi in the first half of 2024, with pricing to follow.

New Indications

• Zoryve® (roflumilast 0.3% cream): The FDA approved a new indication for Arcutis’ phosphodiesterase 4 (PDE4) inhibitor Zoryve for the topical treatment of plaque psoriasis in patients 6 years of age and older.[10]
• Veltassa®  (patiromer): The potassium binder Veltassa, by Vifor, received an expanded indication for hyperkalemia to include pediatric patients 12 years and older.[11] In those 12 to 17 years of age, the recommended starting dose is 4 grams orally once daily. The dose can be adjusted based on serum potassium level.

Generic Launches

• Onexton® (clindamycin phosphate-benzoyl peroxide, gel, 1.2-3.75%): Taro launched their generic version of Bausch Health’s Onexton for the treatment of acne vulgaris.  Multiple manufacturers are set to launch their generic versions in the first half of 2024.  Onexton generated $118 million in U.S. annual sales in 2022.
• Mydayis (amphetamine-dextroamphetamine, 3-bead cap ER 24hr, 12.5 mg, 25 mg, 37.5 mg, 50 mg): Teva launched their generic version of Shire’s Mydayis for attention deficit hyperactivity disorder.  Multiple manufacturers are anticipated to launch their generic version in 2023. Mydayis generated $97 million U.S. annual sales in 2022.
• *Votrient (pazopanib tab, 200 mg): Multiple manufacturers have launched their generic version of Novartis’ Votrient for renal cell carcinoma and soft tissue sarcoma.  Votrient generated $215 million in U.S. annual sales in 2022.

*Specialty medication

[1] https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/213931s000lbl.pdf.

[2] https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/213931s000lbl.pdf.

[3] BLOCK. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442342.

[4] PHREEDOM. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785778/pdf/KID.0002002021.pdf.

[5] https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217836s000lbl.pdf.

[6] https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215320s000lbl.pdf.

[7] https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216632s000lbl.pdf.

[8] https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216755s000lbl.pdf.

[9] https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021164s000lbl.pdf.

[10] https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215985s002lbl.pdf.

[11] https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/205739s038lbl.pdf.