May 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).

1H2021: Leukotac® (inolimomab)

The FDA is reviewing Farmaceutici Spa’s Leukotac for treatment of steroid-refractory acute graft-versus-host disease (aGvHD), grade II-IV adult patients. Leukotac is seeking approval based on the Phase 3 INO107 clinical trial, which demonstrated overall survival (OS) at one year of 46.9% in Leukotac patients compared to 39.2% in the anti-thymo globulin (ATG) patients.1 The time to treatment failure between the arms did not achieve statistical significance. Long-term follow-up data for INO107 concluded that at the median duration of 58.4 months, 30.6% of patients from the Leukotac were alive, compared to 19.6% of patients from the ATG arm, which was statistically significant.1

1H2021: FKB238 (bevacizumab biosimilar)

Centus Biotherapeutics’ FKB238 is seeking approval from the FDA as biosimilar for Roche’s Avastin® (bevacizumab) for indications including:

• metastatic carcinoma of the colon or rectum
• metastatic breast cancer
• unresectable advanced, metastatic or recurrent non-small cell lung cancer
• advanced and/or metastatic renal cell cancer
• epithelial ovarian, fallopian tube, or primary peritoneal cancer
• persistent, recurrent, or metastatic carcinoma of the cervix

FKB238 is applying for approval based on the Phase 3 clinical trial that demonstrated equivalent pharmacokinetic and pharmacodynamic profiles when compared to bevacizumab.2 Currently, there are two other bevacizumab biosimilar products that have launched: Amgen’s Mvasi® (bevacizumab-awwb) and Pfizer’s Zirabev® (bevacizumab-bvzr).

2Q2021: tanezumab

The FDA is reviewing Pfizer And Lilly’s tanezumab for treatment of chronic pain in patients with moderate-to-severe osteoarthritis (OA). Tanezumab is a monoclonal antibody nerve growth factor inhibitor that is administered subcutaneously once every eight weeks by a health care professional. In clinical trials, tanezumab 2.5mg demonstrated more pain reduction than placebo; however, the pain reduction was no different compared to NSAIDs. Tanezumab increased the risk of rapidly progressive OA and total joint replacement compared to other treatment options and placebo.3 Similar products include generic NSAIDs or Pfizer’s Celebrex® (celecoxib).

5/9/2021: tralokinumab

The FDA is reviewing Leo Pharma’s tralokinumab for the treatment of adults with moderate to severe atopic dermatitis. Tralokinumab targets interleukin-13 (IL-13) and is self-administered subcutaneously once every two weeks. Tralokinumab was evaluated against placebo, alone and in combination therapy with topical corticosteroids. Based on Phase 3 trials, ECZTRA 1, 2, and 3, tralokinumab demonstrated safety and efficacy compared to placebo while meeting its primary and secondary endpoints at week 16 as assessed by the Investigator Global Assessment (IGA) score of clear or almost clear skin (IGA 0/1) and at least a 75% improvement in the Eczema Area and Severity Index score (EASI-75).4 In ECZTRA 1 and 2, the majority of patients treated with tralokinumab achieved a clinical response at week 16 and maintained it through week 52 without use of topical corticosteroids. In ECZTRA 3, nine out of 10 patients who achieved clear or almost clear skin with tralokinumab 300mg in combination with topical corticosteroids at week 16 were able to maintain through week 32. Similar products include Sanofi’s Dupixent® (dupilumab).

5/13/2021: HTX-011 (bupivacaine and meloxicam)

Heron Therapeutics’ HTX-011 (bupivacaine and meloxicam) combination product is seeking approval from the FDA as an injection for management of postoperative pain.

This injection uses Heron’s Biochronomer delivery technology for local administration into the surgical site. Phase 3 studies demonstrated significant reduction in pain and opioid use through 72 hours compared to bupivacaine solution, which is the current standard-of-care local anesthetic for postoperative pain control.5 Similar products include Pfizer’s Marcaine® (bupivacaine hydrochloride), and Boehringer Ingelheim’s Mobic® (meloxicam).

5/14/2021: pegcetacoplan

Apellis Pharmaceuticals’ pegcetacoplan is seeking approval from the FDA for treatment of paroxysmal nocturnal hemoglobinuria (PNH). Pegcetacoplan is a synthetic cyclic peptide conjugated to a polyethylene glycol polymer that binds specifically to C3 and C3b.?Pegcetacoplan met its primary endpoint in a Phase 3, PEGASUS study, demonstrating superiority to Soliris® (eculizumab, a C5 inhibitor) with an improvement in adjusted means of 3.8g/dL of hemoglobin.6 Additionally, 85% of patients treated with pegcetacoplan were transfusion free. Similar products include Alexion Pharmaceuticals’ Soliris & Alexion Pharmaceuticals’ Ultomiris® (ravulizumab-cwvz).

5/18/2021: avalglucosidase alfa

The FDA granted priority review to Sanofi-Aventis’ 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. In clinical trials, avalglucosidase alfa demonstrated it was safe and well-tolerated with no serious adverse events. From baseline, investigators observed greater improvements in percent-predicted forced vital capacity (FVC) at all clinical timepoints with avalglucosidase alfa compared to standard therapy. Additionally, avalglucosidase alfa had a 2.43% overall greater increase in FVC at 49 weeks which achieved statistical noninferiority. Avalglucosidase alfa treated patients experienced greater improvements in the 6-minute walk test (6MWT), at both meters (30.01) and percent-predicted FVC (4.71%).7

5/21/2021: loncastuximab tesirine (Lonca)

ADC Therapeutics’ loncastuximab tesirine (Lonca) has been granted priority review for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Lonca is a humanized monoclonal antibody that binds to human CD19. It is a 30-minute health care administered intravenous infusion. In an open-label, single-arm, Phase 2 clinical trial, Lonca demonstrated an overall response rate (ORR) of 48.3% and a complete response (CR) rate of 24.1%.8 The median duration of response was 10.25 months. Similar products include Karyopharm Therapeutics’ Xpovio® (selinexor), MorphoSys AG’s Monjuvi® (tafasitamab-cxix), Kite’s Yescarta® (tisagenlecleucel) and Novartis Pharmaceuticals’ Kymriah® (tisagenlecleucel).

5/27/2021: DS-100 (dehydrated alcohol injection)

Eton Pharmaceuticals’ DS-100 is being reviewed by the FDA as an injectable formulation of dehydrated alcohol for treatment of methanol poisoning. DS-100 is seeking approval via the 505(b)2 pathway using alcohol as its reference product. COVID-19 related demand for hand sanitizer has led manufacturers to improperly use toxic methanol in their products, leading to an epidemic of methanol poisoning. The FDA recommended recalls of more than 150 hand sanitizers due to methanol poisoning risk.9 Similar products include generic fomepizole.

5/27/2021: Camcevi® 42mg (leuprolide mesylate 50mg depot)

Foresee Pharmaceuticals’ Camcevi 42 is seeking approval from the FDA as a ready-to-use six-month injectable suspension formulation of the anti-androgen using Foresee’s stabilized injectable formulation (SIF) depot delivery technology for palliative treatment of advanced prostate cancer. Camcevi 42mg is applying for approval via the 505(b)2 pathway using Tolmar’s Eligard® (leuprolide acetate for injectable) as a reference product. A Phase 3 study demonstrated that Camcevi 42mg injection every six months was effective, safe and well tolerated.10

5/29/2021: ET-104 (zonisamide oral suspension)

Eton Pharmaceuticals’ ET-104 is being reviewed by the FDA as an oral liquid formulation of the anticonvulsant for treatment of partial seizures in epilepsy patients, including pediatric patients. Based on IQVIA data, more than 150,000 prescriptions of zonisamide are written annually for the treatment of epilepsy.11 This will be a liquid product that allows easier dosing for pediatric patients and patients with dysphagia. ET-104 is applying via the 505(b)(2) pathway that uses Sunovion Pharms’ Zonegran® (zonisamide) as its reference product.

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.targetedonc.com/view/fda-approval-sought-for-inolimomab-in-steroid-refractory-acute-gvhd

2. https://www.centerforbiosimilars.com/view/genentech-files-to-block-marketing-of-centus-bevacizumab-biosimilar

3. https://investor.lilly.com/news-releases/news-release-details/us-fda-accepts-regulatory-submission-tanezumab-potential-first

4. https://www.businesswire.com/news/home/20200612005247/en/Tralokinumab-Achieves-Primary-and-Secondary-Endpoints-in-Three-Pivotal-Phase-3-Trials-in-Adult-Patients-with-Moderate-to-Severe-Atopic-Dermatitis

5. https://www.herontx.com/HTX-011#:~:text=HTX%2D011%20(bupivacaine%20and%20meloxicam,the%20need%20for%20opioid%20analgesics.

6. https://www.biospace.com/article/releases/apellis-and-sobi-the-new-england-journal-of-medicine-publishes-phase-3-pegasus-study-results-comparing-pegcetacoplan-to-eculizumab-for-pnh/

7. https://pompediseasenews.com/avalglucosidase-alfa-pompe-disease-enzyme-replacement-therapy/

8. https://www.businesswire.com/news/home/20201207005264/en/ADC-Therapeutics-Announces-Updated-Clinical-Data-on-Lead-Antibody-Drug-Conjugate-Programs-Loncastuximab-Tesirine-Lonca-and-Camidanlumab-Tesirine-Cami-Presented-at-62nd-American-Society-of-Hematology-Annual-Meeting

9. https://www.globenewswire.com/news-release/2020/07/27/2067815/0/en/Eton-Pharmaceuticals-Submits-New-Drug-Application-to-the-FDA-for-Orphan-Drug-Dehydrated-Alcohol-Injection-DS-100.html

10. https://www.biospace.com/article/foresee-pharmaceuticals-announces-submission-of-nda-for-fda-approval-of-lmis-50mg/

11. https://www.globenewswire.com/news-release/2020/07/30/2070328/0/en/Eton-Pharmaceuticals-Submits-New-Drug-Application-to-the-FDA-for-Zonisamide-Oral-Suspension-ET-104.html