April 2023 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).

Drug pipeline for April 2023

4/2/2023: mirikizumab
The FDA is reviewing Lilly’s mirikizumab for treatment of moderately-to-severely active ulcerative colitis. Mirikizumab is a humanized IgG4 monoclonal antibody that binds to the p19 subunit of interleukin 23. It is seeking approval based on the Phase 3 LUCENT-1 trial that tested patients with moderately-to-severely active ulcerative colitis who have previously failed conventional and/or biologic therapies and/or JAK inhibitors. Mirikizumab achieved statistically superior rates of clinical remission at 12 weeks compared to patients taking placebo (24.2% compared to 13.3%). Among patients who had responded to 12-week induction treatment with mirikizumab, nearly 50% of patients receiving mirikizumab maintenance treatment achieved clinical remission at one year compared to 25% of patients on placebo. Nearly two-thirds of patients receiving mirikizumab who achieved clinical remission at 12 weeks maintained clinical remission at one year (63.6%) compared to one-third of patients on placebo (36.9%). Nearly all patients receiving mirikizumab who achieved clinical remission at one year were not taking corticosteroids for at least three months prior to the end of maintenance treatment (97.8%).¹ Mirikizumab is administered intravenously (IV) to start but then transitions to monthly subcutaneous self-administered injections.  Similar products include AbbVie’s Humira^® (adalimumab), Janssen biotech’s Remicade^® (infliximab) and their biosimilars.

4/6/2023: letibotulinumtoxinA
The FDA is reviewing Hugel America’s letibotulinumtoxinA as a botulinum toxin for treatment of moderate to severe glabellar (frown) lines in adults. LetibotulinumtoxinA met its primary endpoint of improving the facial wrinkle scale (FWS) at week four compared to baseline.² LetibotulinumtoxinA is currently approved and available in 28 countries. Similar products include Allergan’s Botox^® (onabotulinumtoxinA).

 4/17/2023: Rizafilm™ (rizatriptan)
The FDA is reviewing IntelGenx and Gensco’s Rizafilm for treatment of acute migraines. Rizafilm is an orally disintegrating film formulation of the 5-HT1 receptor antagonist designed to be bioequivalent to Merck’s orally disintegrating rizatriptan product Maxalt MLT. Rizafilm is seeking approval through the 505(b)(2) using Merck’s Maxalt-MLT as its reference drug.³ Similar products include other generic triptans.

4/24/2023: quizartinib
Daiichi Sankyo’s quizartinib has been granted priority review by the FDA for treatment of adults with newly diagnosed acute myeloid leukemia (AML) that are FLT3-ITD positive. Quizartinib is an oral, selective type II FMS-like tyrosine kinase 3 (FLT3) inhibitor for use in combination with standard cytarabine and anthracycline induction and cytarabine consolidation chemotherapy, and as continuation monotherapy following consolidation. Quizartinib is seeking approval based on the Phase 3 QuANTUM-First study that achieved a statistically significant overall survival (OS) rate. In QuANTUM-First, quizartinib combined with standard induction and consolidation chemotherapy and then continued as a single agent in newly diagnosed FLT3-ITD positive AML demonstrated a 22.4% reduction in the risk of death compared to standard chemotherapy alone. After a median follow-up of 39.2 months, median OS was more than double at 31.9 months for patients receiving quizartinib compared to 15.1 months for patients receiving chemotherapy.⁴ Similar products include Novartis’ Rydapt^® (midostaurin).

4/25/2023: tofersen
The FDA granted priority review of Biogen’s tofersen for treatment of amyotrophic lateral sclerosis (SOD1-ALS). Mutations in the SOD1 gene account for only 12-20% of familial ALS and 1-2 % of sporadic ALS cases (approximately 330 people in the US). Scientists do not understand fully how SOD1 mutations cause ALS but think that they lead to the formation of superoxide dismutase aggregates that are harmful to the cells. Tofersen is administered into the spinal canal and is an RNA-based therapy designed to reduce toxic SOD1 protein and preserve cell function.  Biogen is seeking approval of tofersen under the FDA’s accelerated approval pathway, based on the use of neurofilament as a surrogate biomarker that is reasonably likely to predict clinical benefit. Tofersen’s application was based on data from the three part VALOR trial. Toferson missed its primary endpoint in the Phase 3 VALOR trial. The trial showed a non-statistically-significant 1.2-point difference on the ALSFRS-R scale.⁵ The FDA will hold an Advisory Committee meeting on March 22, 2023. Currently, there are no specific treatments for SOD1-ALS.

4/26/2023: SER-109 (consortium of highly purified Firmicutes spores)
The FDA is reviewing Seres Therapeutics’ SER-109 as a microbiome therapeutic designed to modulate the disrupted microbiome to a state that resists C difficile colonization and growth for prevention of recurrent C difficile infection. SER-109 is an oral medication administered as 4 capsules daily for 3 days. It is seeking approval based on the Phase 3 ECOSPOR III study which demonstrated at week 1, the proportion of patients with overall improvement from baseline was 49.4% in the SER-109 group and 26.9% in the placebo group. At week 8, this rose to 66.3% improvement in the SER-109 group versus 48.4% in the placebo group.⁶ Similar products include Ferring Pharmaceticals’ Rebyota™.

4/27/2023: aripiprazole 2-month, ready-to-use injectable
Otsuka and Lundbeck’s aripiprazole two-month, ready-to-use injectable, is seeking approval from the FDA for the treatment of schizophrenia in adults and for maintenance monotherapy treatment of bipolar I disorder in adults. It has dosing every two months via intramuscular injection in the gluteal muscle.⁷ Aripiprazole 2-month, ready-to-use injectable is seeking approval via the 505(b)(2) pathway using Otsuka’s Abilify Maintena™ (aripiprazole) as its reference product.

4/28/2023: RiVive^® (naloxone 3mg nasal spray)
Harm Reduction Therapeutics’ RiVive is seeking approval as an over the counter (OTC) switch of the opioid antagonist formulated as a 3mg nasal spray for treatment of a known or suspected opioid overdose emergency. Based on provisional Centers for Disease Control and Prevention data, over 107,000 overdose deaths occurred in the 12-month period ending in August 2022.⁸ RiVive is seeking approval through the 505(b)2 pathway using Emergent’s Narcan^® (naloxone) as its reference product.

4/30/2023: TransCon PTH (palopegteriparatide)
Ascendis’ TransCon PTH is seeking approval from the FDA for treatment of adults with hypoparathyroidism. TransCon PTH is a prodrug of the parathyroid hormone in development as a once-daily hormone replacement therapy. The Phase 3 PaTHway trial found that at 26 weeks, 78.7% of patients who received TransCon PTH achieved the primary endpoint of albumin-adjusted serum calcium within the normal range and independence from conventional therapy with active vitamin D and therapeutic doses of calcium compared to 4.8% of patients receiving placebo.⁹ Similar products include Takeda’s Natpara^® (parathyroid hormone); however, in October 2022 Takeda announced that it will discontinue manufacturing of Natpara by the end of 2024.

Contact your Prime representative for more information or with any questions you have about drugs in the pipeline.

References

1. https://investor.lilly.com/news-releases/news-release-details/nearly-two-thirds-patients-respond-mirikizumab-treatment-12#:~:text=Mirikizumab%20is%20a%20humanized%20IgG4,ulcerative%20colitis%20and%20Crohn’s%20disease.
2. https://www.businesswire.com/news/home/20221025005825/en/Hugel-Aesthetics-Receives-FDA-Acceptance-of-BLA-Resubmission-for-LetibotulinumtoxinA-for-Injection-for-Glabellar-Lines
3. https://www.globenewswire.com/news-release/2022/11/22/2560714/0/en/IntelGenx-Receives-FDA-PDUFA-Date-for-RIZAFILM.html
4. https://www.cancernetwork.com/view/fda-grants-priority-review-to-quizartinib-for-newly-diagnosed-flt3-itd-aml
5. https://alsnewstoday.com/news/fda-seeks-input-tofersen-approval-als/#:~:text=Tofersen%2C%20administered%20by%20intrathecal%20injection,protein%20and%20preserve%20cell%20function.
6. https://www.contagionlive.com/view/ser-109-significantly-improves-quality-of-life-for-patients
7. https://www.otsuka-us.com/news/otsuka-and-lundbeck-announce-us-fda-acceptance-new-drug-application-aripiprazole-2-month-ready#:~:text=long%2Dacting%20injectable-,Aripiprazole%202%2Dmonth%2C%20ready%2Dto%2Duse%20long%2D,indicated%20for%20once%2Dmonthly%20ABILIFY
8. https://www.fda.gov/drugs/news-events-human-drugs/our-perspective-cders-continued-efforts-widen-naloxone-access
9. https://www.empr.com/home/news/drugs-in-the-pipeline/transcon-pth-gets-priority-review-for-hypoparathyroidism/