August 2021 decisions expected from the FDA

---

At Prime Therapeutics (Prime), we’ve positioned ourselves to best prepare our clients to manage new drugs. Our clinical and trade relations teams keep a keen eye on drugs likely to be approved by the U.S. Food and Drug Administration (FDA).

8/1/2021: Twyneo® (benzoyl peroxide and tretinoin)

The FDA is reviewing Sol-Gel Technologies’ Twyneo as an investigational proprietary fixed-dose combination of 3% encapsulated benzoyl peroxide and 0.1% encapsulated tretinoin cream for the treatment of acne vulgaris. The application is based on two Phase 3 trials that compare Twyneo to vehicle. Twyneo demonstrated statistically significant improvements compared to vehicle on the proportion of patients who had at least a two-point grade reduction from baseline as well as “clear” (0) or “almost clear” (1) at week 12, based on a 5-point Investigator’s Global Assessment scale. Additionally, a statistically significant improvement was observed with Twyneo regarding inflammatory and non-inflammatory lesion counts.1 Similar products include generic tretinoin.

8/1/2021: Uptravi® IV (selexipag)

Johnson & Johnson Healthcare’s Uptravi IV is being evaluated by the FDA for treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adults with WHO functional class (FC) II-III who are currently prescribed oral Uptravi but are temporarily unable to take oral therapy. Uptravi IV is an intravenous injection formulation of the selective prostacyclin IP receptor agonist. Oral Uptravi was approved by the FDA in 2015 for the treatment of PAH to delay disease progression and reduce the risk of hospitalization. Uptravi’s application is based on a Phase 3 study that evaluated the safety and tolerability of patients with PAH temporarily switching from oral Uptravi to Uptravi IV, and then transitioning back to the initial oral dose. Results showed that Uptravi IV is suitable to maintain continuous dosing for short periods of time when oral administration is not feasible.2 Similar products include Janssen’s Uptravi® Oral (selexipag) and United Therapeutics’ Orenitram® (treprostinil).

8/6/2021: ET-101 (topiramate oral solution)

Azurity Pharmaceuticals’ ET-101 is seeking approval from the FDA as an oral liquid formulation of the anticonvulsant for:

• Monotherapy treatment of partial-onset or primary general tonic-clonic seizures in pediatric patients aged two years and older;
• Adjunctive therapy for partial-onset seizures, including Lennox-Gastaut syndrome, in patients aged two years and older; and for
• Preventative treatment of migraine in patients 12 years and older.

ET-101 is applying via the 505(b)(2) pathway using Janssen’s Topamax® (topiramate) as its reference product.3 Similar products include generic topiramate tablets.

8/18/2021: Vicinium® (oportuzumab monatox)

The FDA is reviewing Sensen’s Vicnium for BCG-unresponsive non-muscle invasive bladder cancer (NMBIC). Vicinium works by binding to a protein called epithelial cell adhesion molecule (EpCAM) on the surface of epithelial cells and some types of cancer cells. Vicinium is seeking approval based on an open-label, Phase 3 study without comparator that demonstrated a three-month complete response (CR) rate of 42%.4 Similar products include Merck’s Keytruda® (pembrolizumab).

8/18/2021: avalglucosidase alfa

The FDA granted priority review to Sanofi’s avalglucosidase alfa as an investigational enzyme replacement therapy for treatment of patients with Pompe disease (glycogen storage disease type II). Pompe disease is a rare disorder in which glycogen builds up within cells which causes muscle weakness and trouble breathing. The only FDA-approved enzyme replacement therapy for Pompe patients is Lumizyme® (alglycosidase alfa), also from Sanofi. A double-blind Lumizyme-controlled trial found that avalglucosidase was non-inferior but not superior to Lumizyme for the primary endpoint of percent-predicated forced vital capacity (FVC) compared to the standard of care. In clinical trials, avalglucosidase alfa demonstrated it was safe and well-tolerated with no serious adverse events.5

8/2021: SaphneloTM (anifrolumab-fnia)

The FDA is reviewing Astrazeneca’s Saphnelo, a type 1 interferon inhibitor, for treatment of adults with moderate to severe systemic lupus erythematosus (SLE). Saphnelo is administered 300mg intravenously (IV) once every four weeks. Saphnelo was evaluated for safety and efficacy compared with placebo in a Phase 3 clinical trial TULIP-1 which failed to meet its primary endpoint, a higher percentage of people on placebo achieved the required response. In another Phase 3 clinical trial, TULIP-2, Saphnelo achieved a statistically significant response of 47.8% of patients compared to 31.5% placebo patients (p<0.05).6 Similar products include GSK’s Benlysta® (belimumab), Sanofi’s Plaquenil® (hydroxychloroquine) and prednisolone.

8/22/2021: AXS-05 (dextromethorphan and bupropion)

Axsome Therapeutics’ AXS-05 is being reviewed by the FDA for the treatment of major depressive disorder (MDD). AXS-05 is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, also known as a glutamate receptor modulator. AXS-05’s application is based on a Phase 3 controlled trial, GEMINI, that demonstrated a statistically significant reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score compared with placebo at week six (16.6 points for AXS-05 vs 11.9 points for placebo). AXS-05 was also associated with a significant improvement on the Clinical Global Impression of Improvement (CGI-I) scale at week six compared with placebo.7 Similar products include generic bupropion.

8/23/2021: Korsuva® (difelikefalin)

Cara Therapeutics’ Korsuva is being reviewed by the FDA for the treatment of moderate to severe pruritis in hemodialysis patients. Korsuva is a peripherally acting kappa opioid receptor (KOR) agonist and is administered 0.5mcg/kg intravenously three times per week after each dialysis session. Korsuva is seeking approval based on two Phase 3 clinical trials, KALM-1 and KALM-2, which evaluated the proportion of patients itching based on Worst Itching Intensity Numerical Rating Scale (WI-NRS). KALM-1 demonstrated a decrease by at least three points in the WI-NRS score compared to placebo (49.1% vs 27.9%) which was statistically significant. KALM-2 trial demonstrated a 54% decrease in Korsuva patients’ itch compared to 42% reduction in placebo patients’ itch which was also statistically significant.8 Similar products include generic gabapentin and Pfizer’s Lyrica® (pregabalin).

8/30/2021: belumosudil

(KD0umosudil is being reviewed by the FDA for the treatment of patients with chronic graft-versus-host disease (cGVHD). Belumosudil is an oral selective inhibitor of Rho-associated coiled-coil kinase 2. Belumosudil is seeking approval based on an open-label, Phase 2 ROCKstar clinical trial which demonstrated treatment with belumosudil once daily led to an overall response rate (ORR) of 73%; and the twice daily dose achieved an ORR of 74%. Belumosudil had a median time to response of four weeks. At six weeks, patients in the study showed a failure-free survival rate of 77%.9 Similar products include Incyte Corp’s Jakafi® (ruxolitinib) and AbbVie’s Imbruvica® (ibrutinib).

While the information in this newsletter is from sources we believe to be reliable, we do not warrant that the information in this document is free from error. Use it only as a guide. Statements regarding drugs or manufacturers are not intended as promotion; those statements should not be used to make assumptions about formulary status. Each trademarked drug name is the property of its respective owner.

---

References

1. https://www.empr.com/home/news/drugs-in-the-pipeline/twyneo-fixed-dose-combination-tretinoin-retinoid-benzolyl-peroxide/
2. https://www.prnewswire.com/news-releases/new-real-world-observational-analysis-of-uptravi-selexipag-underscores-the-importance-of-risk-assessment-for-treating-pulmonary-arterial-hypertension-pah-patients-301261613.html
3. https://www.globenewswire.com/en/news-release/2020/10/06/2104593/0/en/Eton-Pharmaceuticals-Submits-New-Drug-Application-to-the-FDA-for-Topiramate-Oral-Solution-ET-101.html
4. http://www.io.nihr.ac.uk/wp-content/uploads/2020/07/8019-TSID_10009-Oportuzumab-Monatox-for-Non-muscle-Invasive-Bladder-Cancer-V1.0-JULY2020-NON-CONF.pdf
5. https://www.neurologylive.com/view/fda-accepts-bla-for-avalglucosidase-alfa-for-pompe-disease
6. https://www.clinicaltrialsarena.com/news/astrazeneca-anifrolumab-post-hoc/
7. https://www.biospace.com/article/axsome-therapeutics-axs-05-priority-review-by-fda-could-speed-up-help-for-mdd-patients/
8. https://www.globenewswire.com/en/news-release/2021/04/29/2219547/29236/en/Cara-Therapeutics-Announces-Topline-Results-From-KARE-Phase-2-Dose-Ranging-Trial-of-Oral-KORSUVA-in-Atopic-Dermatitis-Patients-with-Moderate-to-Severe-Pruritus.html
9. https://www.targetedonc.com/view/fda-postpones-approval-decision-on-belumosudil-for-chronic-graft-versus-host-disease