December 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).

12/2021: LV-101 (intranasal carbetocin)
The FDA has granted priority review of Levo Therapeutics’ LV-101 (intranasal carbetocin) for treatment for hyperphagia and behavioral distress associated with Prader-Willi syndrome (PWS). PWS is a rare, complex, neurodevelopmental disorder that occurs in approximately 1 in 16,000 births. It is characterized by a false state of starvation and associated hyperphagia (unrelenting hunger), to which a deficiency in oxytocin is believed to be contributory. LV-101 is a selective oxytocin-receptor agonist that is inhaled through the nose three times a day before meals. LV-101’s application is being reviewed based on the Phase 3 CARE-PWS trial that tested two doses (9.6mg primary endpoint and 3.2mg secondary endpoint) compared against placebo. In the trial, the 9.6mg dose did not meet the primary outcome, as it failed to reduce hyperphagia or obsessive-compulsive behaviors. Additionally, the 3.2mg dose did not reduce obsessive-compulsive behaviors. LV-101 3.2mg led to statistically significant reduction in hyperphagia, anxiety, and distress over an eight-week treatment period.¹ The FDA Psychopharmacologic Drugs Advisory Committee voted 12 to 1 against approval.² There are currently no similar products approved for this indication.

12/7/2021: DARE-BV1 (clindamycin 2% hydrogel)
Daré Bioscience’s DARE-BV1 is being reviewed by the FDA for treatment of bacterial vaginosis. DARE-BV1 is a hydrogel formulation of the antibiotic for a one-time vaginally administered dose. DARE-BV1 was evaluated in the Phase 3 trial, DARE-BVFREE, which demonstrated the efficacy and safety of DARE-BV1 against placebo. Treatment with DARE-BV1 was found to be statistically superior to placebo at day 21-30 in the intent-to-treat population with 70% of patients clinically cured compared with 36% for placebo. In the per protocol population, DARE-BV1 demonstrated clinical cure rates of 77% at day 21 to 30 and 81% at day 7 to 14 compared with 43% and 30% for placebo, respectively.³ Similar products include generic metronidazole vaginal gel.

12/15/2021: Brixadi^® (buprenorphine depot)
Brixadi by Braeburn Pharmaceuticals is being reviewed by the FDA for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine. Brixadi is a long-acting weekly and monthly subcutaneous injection formulation for administration by a health care professional. Patients currently being treated with other buprenorphine-containing products can start treatment with either Brixadi weekly or Brixadi monthly. Brixadi met the primary endpoint of non-inferiority for responder rate compared to once daily sublingual buprenorphine/naloxone in its clinical trial. The trial included real-world patients; 26% tested positive for fentanyl prior to study randomization, 71% were using heroin at study initiation and 52% were using injectable opioids at study initiation.⁴ Similar products include generic buprenorphine.

12/15/2021: Nefecon^® [targeted release formulation (TRF)-budesonide]
Calliditas Therapeutics’ Nefecon is seeking accelerated approval from the FDA for treatment of primary IgA nephropathy (IgAN) also known as Berger’s disease. Primary IgA nephropathy is a rare disease that affects the kidney but is caused by overproduction of antibodies produced in the lining of the small intestine, for which there are no approved medications. Berger’s disease affects 130,000-150,000 people in the U.S. The NDA is based on data from the Phase 3, NefIgArd study, which achieved its primary end point of a significant proteinuria reduction versus placebo at nine months.⁵ The mean proteinuria reduction from baseline was 31% in the TRF-budesonide (16 mg) arm compared to 5% in the placebo arm.⁵

12/17/2021: efgartigimod
Argenx’s efgartigimod is being reviewed by the FDA for treatment of generalized myasthenia gravis (gMG). Efgartigimod is a first-in-class investigational antibody fragment to target the neonatal Fc receptor (FcRn). A Phase 3 clinical trial, ADAPT, evaluated efgartigimod’s safety and effectiveness compared to placebo. The trial enrolled patients both with and without antibodies against acetylcholine receptors (AChR). Participants were randomized to either efgartigimod at 10mg/kg or to a placebo, in addition to their current standard treatments, for 26 weeks. Efgartigimod demonstrated improvements in the symptoms in a significantly bigger proportion of patients than placebo. Patients who tested positive for acetylcholine receptor (AChR+) antibody had a 67.7% response rate in Myasthenia Gravis Activities of Daily Living (MG-ADL) score, compared to 29.7% response rate in placebo patients. As for duration of treatment response, 56.8% of patients responded to efgartigimod for at least eight weeks, and 34.1% at least 12 weeks.⁶ Similar products include Alexion Pharmaceuticals’ Soliris^® (eculizumab).

12/2021: Tadfin™ (tadalafil and finasteride capsule)
The FDA is reviewing Veru’s Tadfin™ a combination of tadalafil 5mg and finasteride 5mg for benign prostatic hyperplasia. Tadfin is seeking approval via the 505(b)2 pathway using Eli Lilly’s Cialis^® (tadalafil) and Merck’s Proscar^® (finasteride) as its reference products.⁷ Both tadalafil and finasteride are available generically.

12/2021: CHS-1420 (Humira^® biosimilar)
Coherus Biosciences is seeking approval from the FDA for CHS-1420, a biosimilar of AbbVie’s Humira^® (adalimumab). Coherus reported positive results from a Phase 3 study of CHS-1420 back in 2017. The results demonstrated similarity between CHS‑1420 and Humira.⁸ If approved, Coherus plans to launch the adalimumab biosimilar in the U.S. on or after July 2023.

12/22/2021: dextroamphetamine transdermal system (ATS)
The FDA is reviewing Noven Therapeutics’ dextroamphetamine transdermal system (ATS) for treatment of attention deficit hyperactivity disorder (ADHD) in patients six years of age and older. Dextroamphetamine transdermal system is a patch formulation of the amphetamine in four dosage strengths delivered over nine hours. Dextroamphetamine transdermal system demonstrated significant improvements in ADHD symptoms, as measured by the Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale (SKAMP) total score when compared to placebo.⁹ Similar products include Noven’s Daytrana^® (methylphenidate transdermal systems) and generic dextroamphetamine capsules.

12/24/2021: Libervant^® (diazepam buccal film)
The FDA is reviewing Aquestive Therapeutics’ Libervant, a soluble buccal film formulation of the benzodiazepine using Aquestive’s PharmFilm technology for rapid oral treatment of acute uncontrolled seizures, or seizure clusters, in refractory patients with epilepsy on stable regimens of antiepileptic drugs. A dose crossover study comparing the buccal film to Bausch’s Diastat^® (diazepam rectal gel) demonstrated comparable bioavailability in maximal plasma concentrations, area under the curve and time to maximal concentrations.¹⁰ If approved, Libervant may not be able to launch immediately due to Neurelis’ Valtoco^® (diazepam nasal spray) seven years of orphan drug exclusivity for this indication. Similar products include Bausch’s Diastat^® (diazepam rectal gel), Neurelis’ Valtoco^® (diazepam nasal spray), and UCB’s Nayzilam^® (midazolam).

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.

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References

1. https://www.biospace.com/article/releases/levo-therapeutics-announces-top-line-results-from-phase-3-care-pws-study-of-lv-101-intranasal-carbetocin-for-the-treatment-of-prader-willi-syndrome/
2. https://endpts.com/fda-adcomm-votes-12-1-against-levo-therapeutics-nasal-spray-for-a-disorder-that-causes-insatiable-hunger/
3. https://www.empr.com/home/news/drugs-in-the-pipeline/clindamycin-vaginal-gel-gets-priority-review-for-bacterial-vaginosis/
4. https://www.drugdiscoveryonline.com/doc/braeburn-resubmits-new-drug-application-for-brixadi-buprenorphine-0001
5. https://www.urologytimes.com/view/fda-grants-targeted-release-budesonide-priority-review-for-iga-nephropathy
6. https://www.fiercepharma.com/special-report/efgartigimod-10-most-anticipated-drug-launches-2021
7. https://www.globenewswire.com/en/news-release/2021/02/23/2180486/11676/en/Veru-Submits-New-Drug-Application-for-Proprietary-TADFIN-for-BPH.html
8. https://investors.coherus.com/news-releases/news-release-details/coherus-bla-filing-adalimumab-biosimilar-candidate-accepted-fda
9. https://www.businesswire.com/news/home/20210427005959/en/Noven-to-Present-Pivotal-Study-Results-for-Investigational-Dextroamphetamine-Transdermal-System-for-Pediatric-ADHD-Patients
10. https://www.neurologylive.com/view/diazepam-buccal-film-libervant-comparable-to-rectal-gel-with-good-safety-tolerability-profile