April 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).

1Q2021: SB8 (bevacizumab biosimilar)

The FDA is reviewing Samsung Bioepis and Merck’s SB8, a biosimilar of Genentech’s Avastin® (bevacizumab). Based on Phase 3 trials in patients with metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC), SB8 demonstrated an overall response rate (ORR) of 47.6% compared with 42.8% with a reference bevacizumab. The median progression-free survival was 8.5 months with SB8 compared with 7.9 months with reference bevacizumab.1 There are currently two other Avastin biosimilars that are approved and have launched: Amgen’s Mvasi® (bevacizumab-awwb), and Pfizer’s Zirabev® (bevacizumab-bvzr).

4/1/2021: abrocitinib

Pfizer’s abrocitinib has been granted priority review by the FDA for treatment of moderate-to-severe atopic dermatitis in patients ages 12 years and older. Abrocitinib is an oral, once-daily Janus kinase 1 (JAK1) inhibitor. Abrocitinib is seeking approval based on five Phase 3 clinical trials that demonstrated abrocitinib was statistically superior in skin clearance, disease extent, and severity, as well as rapid improvements in itch versus placebo.2 Pfizer is seeking approval of both the 100mg and 200mg doses, even though clinical trials have shown the higher dose is more effective. Phase 3 clinical trial JADE COMPARE demonstrated abrocitinib 200mg was superior in itch reduction compared to Regeneron’s Dupixent® (dupilumab). If approved, abrocitinib would be the first oral biologic approved for atopic dermatitis.

4/7/2021: brincidofovir

Chimerix’s brincidofovir has been granted priority review by the FDA as a medical countermeasure for smallpox. Brincidofovir is an antiviral using lipid conjugate technology to penetrate cells and release the nucleotide analog cidofovir, formulated as both oral tablets and oral suspension. Although smallpox was certified as eradicated in 1980 by the World Health Organization, it continues to be a potential global threat in today’s interconnected world. Smallpox outbreaks have killed several hundred million people over the course of several centuries.3 Similar products include SIGA Technologies, Inc.’s Tpoxx® (tecovirmat).

4/15/2021: Eohilia® (budesonide oral suspension, formerly TAK-721)

The FDA has granted priority review of Takeda pharmaceuticals’ Eohilia for the treatment of localized esophageal inflammation caused by eosinophilic esophagitis (EoE). Eohilia is an oral viscous formulation of budesonide. EoE is a chronic inflammatory disease that can cause damage to the esophagus. It impacts approximately one in 2,000 people in the U.S.4 Currently there are no FDA-approved treatments for EoE. Eohilia is seeking approval via the 505(b)(2) pathway using Perrigo’s Entocort EC® (budesonide) as a reference product.

4/16/2021: Estelle® (estetrol and drospirenone) (E4/DRSP)

The FDA is reviewing Mayne Pharma’s Estelle as a combination product for pregnancy prevention. Estelle is composed of 15mg estetrol (E4) and 3mg of drospirenone (DRSP). Estetrol is a native estrogen that has minimal impact on liver cells and metabolic pathways. Estelle is seeking approval based on Phase 3 clinical studies that met its primary endpoint of contraceptive efficacy. This was measured by the number of on-treatment pregnancies per 100 women per 12 months of exposure among women ages 16 to 35 years of age.5 Mayne Pharma claims Estelle is more environmentally friendly compared to alternatives currently on the market because E4 creates smaller environment concentrations in aquatic environment (low as 10ng/L) compared to synthetic estrogen ethinylestradiol (EE2) which is considered to be a strong environmental endocrine disruptor that could accumulate in living organisums.6 Similar products include EE/DRSP combination oral contraceptives.

4/26/2021: Epsolay® (benzoyl peroxide)

Sol-Gel technologies’ Epsolay is being reviewed by the FDA as an investigational topical cream containing encapsulated benzoyl peroxide, 5%, for the treatment of papulopustular rosacea. Epsolay is seeking approval based on Phase 3 clinical trials that demonstrated statistically significant improvement in both co-primary endpoints compared to vehicle. Patients treated with Epsolay achieved “clear” or “almost clear” based on the Investigator Global Assessment (IGA) scale. Additionally, patients had absolute mean reduction from baseline in inflammatory lesion count starting as early as Week 2 and continued through Week 12.7 Both trials showed that treatment with Epsolay led to statistically significant improvement based on the number of patients with an IGA score of 0 or 1. Patients treated with Epsolay also had an absolute mean reduction from baseline in inflammatory lesion counts as early as week 2, which continued through week 12. Multiple products containing benzoyl peroxide are available over the counter (OTC).

4/27/2021: pegunigalsidase alfa (PRX-102)

The FDA is reviewing Chiesi Global Rare Diseases and Protalix’s pegunigalsidase alfa for Fabry disease. Pegunigalsidase alfa is a long-acting recombinant, PEGylated, cross-linked alpha-galactosidase-A enzyme produced with Protalix’ ProCellEx plant cell-based protein expression system. Fabry disease is estimated to affect approximately 5,000 to 10,000 people worldwide. Pegunigalsidase alfa is a once monthly IV infusion administered by a healthcare professional. Pegunigalsidase alfa is seeking approval as a Biobetter using Sanofi Genzyme’s Fabrazyme® (agalsidase beta) as a reference product. In clinical trials pegunigalsidase alfa demonstrated a continuous reduction in plasma globotriaosylceramide (GL-3) and LysoGL-3 level with a 90% reduction in LysoGL-3 levels and 68% reduction in GL-3.8 Similar products include Sanofi Genzyme’s Fabrazyme® (agalsidase beta) and Takeda’s Replagel® (agalsidase alfa).

4/29/2021: CPP-1X/sul (eflornithine and sulindac)

Cancer Prevention Pharmaceuticals’ CPP-1X/sul is being reviewed by the FDA for treatment of adults with familial adenomatous polyposis (FAP). FAP is a rare genetic disease that if left untreated progresses to colorectal cancer in nearly 100% of patients.

In clinical trials, CPP-1X/sul prevented more than 90% subsequent pre-cancerous sporadic adenomas in patients with large bowel polyps when compared with placebo. In the overall population, CPP-1X/sul did not demonstrate statistical significance compared to the individual agents. In patients with intact lower GI anatomy (colon, retained rectum or surgical pouch), the data did show statistically significant benefit for CPP-1X/sul compared to both single agents which delayed surgical events in the lower GI for up to four years.9

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.cancernetwork.com/view/fda-accepts-biologics-license-application-bevacizumab-biosimilar

2. https://www.pfizer.com/news/press-release/press-release-detail/fda-grants-priority-review-and-ema-accepts-regulatory

3. https://www.ncbiotech.org/news/chimerixs-potential-smallpox-therapy-gains-fda-priority-review

4. https://www.biospace.com/article/releases/u-s-food-and-drug-administration-accepts-new-drug-application-for-review-grants-priority-review-for-takeda-s-tak-721-budesonide-oral-suspension-for-the-treatment-of-eosinophilic-esophagitis/

5. https://www.empr.com/home/news/drugs-in-the-pipeline/novel-contraceptive-pill-e4drsp-estetrol-dropspirenone-nda-pregnancy/

6. https://www.globenewswire.com/news-release/2020/01/10/1968775/0/en/E4-Paves-the-Road-Towards-a-Revolutionary-Era-of-Environmental-Friendly-Medicines.html

7. https://www.globenewswire.com/news-release/2020/09/10/2092088/0/en/Sol-Gel-Technologies-Announces-FDA-Acceptance-for-Filing-of-New-Drug-Application-for-Epsolay-for-the-Treatment-of-Inflammatory-Lesions-of-Rosacea.html

8. https://www.biospace.com/article/releases/protalix-biotherapeutics-announces-completion-of-the-treatment-period-for-its-phase-iii-bright-clinical-trial-of-pegunigalsidase-alfa-prx-102-for-the-proposed-treatment-of-fabry-disease/

9. https://www.businesswire.com/news/home/20200629005106/en/Cancer-Prevention-Pharmaceuticals-Submits-New-Drug-Application-to-the-FDA-for-CPP-1Xsul-for-Treatment-of-Familial-Adenomatous-Polyposis