September 2020 decisions expected from the FDA

At Prime Therapeutics (Prime), we’ve positioned ourselves to best prepare our clients to manage the new drugs that come on the market. 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 September 2020:
9/1/2020: SB8 (bevacizumab biosimilar)

The U.S. Food and Drug Administration (FDA) is reviewing Samsung Bioepis and Merck’s biosimilar 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 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 Avastin.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).

9/3/2020: CC-486 (azacitidine)

The FDA is reviewing Bristol-Myers Squibb’s CC-486 for maintenance treatment of adult patients with acute myeloid leukemia (AML) who achieved complete remission (CR) or CR with incomplete blood count recovery (CRi) following induction therapy, with or without consolidation treatment, and who are not candidates for, or who choose not to proceed to, hematopoietic stem cell transplantation. CC-486 is an oral formulation with a pharmacokinetic profile distinct from that of injectable azacitidine allows which may provide greater patient convenience. In the Phase 3, QUAZAR AML-001 study, CC-486 improved survival by 31% and improved relapse-free survival by 35% compared with placebo.2 Similar products include IV azacitidine.

9/12/2020: Terlivaz™ (terlipressin)

The FDA is reviewing Mallinckrodt’s Terlivaz for treatment of hepatorenal syndrome type 1 (HRS-1), a syndrome involving acute kidney failure in cirrhosis patients. HRS-1 is an acute and life-threatening syndrome that affects between 30,000 and 40,000 patients in the U.S. annually. The CONFIRM trial used a surrogate endpoint of renal function improvement, avoidance of dialysis and short-term survival to demonstrate that Terlivaz reversed HRS-1 in 29% of patients who were treated with Terlivaz compared to 16% treated with placebo.3 In July 2020, the FDA Advisory Committee voted 8 to 7 to recommend approval of Terlivaz. The panel suggested that the benefits of Terlivaz outweigh the safety risks, Terlivaz and placebo groups experienced serious side effects at roughly the same rate: 65% versus 61%. The most common serious side effect was respiratory failure followed by abdominal pain.4 Patient death rates in the first 30 days were also roughly the same between Terlivaz and placebo: 42% for Terlivaz versus 40% for placebo. Currently there are no approved drug therapies in the U.S. for HRS-1; however, drugs with a similar mechanism of action to Terlivaz (i.e. norepinephrine) are used off-label for HRS-1.

9/20/2020: ofatumumab

Novartis and Genmab are seeking approval from the FDA for a once monthly self-administered injection formulation of ofatumumab, an anti-CD20 monoclonal antibody for treatment of adults with relapsing forms of multiple sclerosis (RMS). The IV infusion formulation of ofatumumab is approved for chronic lymphocytic leukemia as Novartis’ Arzerra® (ofatumumab). Ofatumumab is seeking approval based on two Phase 3 clinical trials that compared ofatumumab to Sanofi’s Aubagio® (teriflunomide). Ofatumumab showed disability worsening risk reduction of 34.4% at three months, and 32.5% at six months. Ofatumumab demonstrated a 97.5% and 93.8% relative reduction in the number of T1 lesions, respectively.5 Disability improvement at six months showed a favorable trend for ofatumumab, but results were not statistically significant. Ofatumumab is anticipated to compete with Roche’s Ocrevus® (ocrelizumab) which is also an anti-CD20 monoclonal antibody but is administered by a health care professional via IV infusion every six months.

9/27/2020: 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.6 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).

9/30/2020: Ryoncil™ (remestemcel-L)

Mesoblast is seeking FDA approval for Ryoncil for treatment of children with steroid-refractory acute graft-versus-host disease (SRaGVHD). Ryoncil is an allogeneic cell therapy that is comprising culture-expanded mesenchymal stromal cells derived from bone marrow of an unrelated donor and administered in a series of intravenous infusions. Three clinical trials of Ryoncil demonstrated that, in an aggregated dataset, 66% (204 of the 309) of patients achieved an overall response at day 28 following a four-week course.7 Results were consistent across all grades of disease, including the most severe. There are currently no FDA-approved treatments for patients 12 years of age and under that experience SRaGVHD. Additionally, Ryoncil is being investigated for the treatment in COVID-19 patients that are experiencing multisystem inflammatory syndrome (MIS-C).8

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

2. https://www.ascopost.com/issues/january-25-2020/oral-cc-486-maintenance-therapy-extends-survival-in-older-patients-with-aml/

3. http://www.mallinckrodt.com/about/news-and-media/news-detail/?id=26706

4. https://www.biospace.com/article/mallinckrodt-s-hrs-1-drug-terlipressin-narrowly-passes-fda-advisory-committee/

5. https://multiplesclerosisnewstoday.com/ofatumumab-for-multiple-sclerosis/

6. https://www.globenewswire.com/news-release/2019/08/06/1897996/0/en/Aquestive-Therapeutics-Announces-Positive-Topline-Results-from-Libervant-Diazepam-Buccal-Film-Single-Dose-Crossover-Study.html

7. https://www.biospace.com/article/releases/clinical-outcomes-using-ryoncil-remestemcel-l-in-children-and-adults-with-severe-inflammatory-graft-versus-host-disease-published-in-three-articles-in-biology-of-blood-and-marrow-transplantation/

8. https://www.biospace.com/article/mesoblast-ltd-s-stem-cell-therapy-shows-83-percent-survival-in-covid-19-patients/