December 2022 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 December 2022

12/14/2022: adagrasib
The United States Food and Drug Administration (FDA) is reviewing Mirati Therapeutics’ adagrasib which is seeking accelerated approval as second-line treatment of advanced non-small cell lung cancer (NSCLC) patients harboring the KRAS G12C mutation following prior systemic therapy. Adagrasib demonstrated an objective response rate (ORR) of 43% and disease control rate of 80% among patients in its Phase 1/2 KRYSTAL-1 trial.¹ Mirati Therapeutics is conducting an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib compared to docetaxel. Similar products include Amgen’s Lumakras^® (sotorasib).

12/23/2022: toripalimab
Junshi Biosciences and Coherus’ toripalimab has been granted priority review from the FDA for two indications: first in combination with gemcitabine and cisplatin for first-line treatment for patients with advanced recurrent or metastatic nasopharyngeal carcinoma and second as monotherapy for second-line or later treatment of recurrent or metastatic NPC patients with disease progression on or after platinum-containing chemotherapy. Toripalimab is seeking approval based on two clinical trials; Phase 2 POLARIS-02 which demonstrated an ORR of 20.5% and Phase 3 JUPITER-02 which demonstrated a median progression-free survival (PFS) of 11.7 months compared to PFS of eight months with chemotherapy alone.² If approved, Coherus plans to launch toripalimab in the United States in the first quarter of 2023. Similar products include Merck’s Keytruda^® (pembrolizumab) and Bristol-Myers Squibb’s Opdivo^® (nivolumab).

12/27/2022: lenacapavir
Gilead Science’s lenacapavir applied for approval from the FDA for treatment of HIV-1 infection in heavily treatment-experienced (HTE) patients with multi-drug resistant (MDR) HIV-1 infection. Lenacapavir is a health-care professional administered HIV-1 capsid inhibitor that is injected subcutaneously every six months along with other antiretrovirals. Lenacapavir is seeking approval based on the clinical trial CAPELLA, a Phase 2/3, placebo-controlled study. The study achieved its primary endpoint by demonstrating that a significantly higher proportion of participants randomly allocated to receive lenacapavir in addition to other antiretrovirals achieved a clinically meaningful viral load reduction of at least 0.5 log₁₀ copies/mL from baseline compared with those receiving placebo plus antiretrovirals during the 14-day functional monotherapy period (88% compared to 17%).³ Similar products include ViiV’s Cabenuva^® (cabotegravir/rilpivirine).

12/28/2022: ublituximab
The FDA is reviewing TG Therapeutics’ ublituximab for the treatment of relapsing multiple sclerosis. TG’s application is seeking approval based on two Phase 3 clinical trials, ULTIMATE 1 and ULTIMATE 2 which evaluated an annualized relapsed rate (ARR) as its primary endpoint. In the ULTIMATE I trial, patients treated with ublituximab resulted in an ARR of 0.08 compared to 0.19 for teriflunomide treated patients. The ULTIMATE II trial resulted in an ARR of 0.09 compared with 0.18, respectively.⁴ If approved, ublituximab will be the first B-cell therapy for use in RMS that can be given as a one-hour infusion every six months after the first dose. Two other anti-CD20 antibodies, Ocrevus^® (ocrelizumab) and Kesimpta^® (ofatumumab), are approved by the FDA to treat relapsing forms of MS, including relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS).

12/29/2022: palovarotene
The FDA has granted priority review to Ipsen/Clementia’s palovarotene for prevention of heterotopic ossification (new bone formation) in patients with fibrodysplasia ossificans progressiva (FOP). FOP has an estimated prevalence of 1.36 per million individuals; however, the number of confirmed cases varies by country.⁵ Palovarotene is an oral selective retinoic-acid receptor gamma (RARγ) agonist. Palovarotene is seeking approval based on the open-label Phase 3 trial single-treatment arm trial in which all subjects receive palovarotene dosing in order to evaluate the safety and dosing regimen. The FDA postponed their adcomm meeting that was set for October 31 in order to review new information, which has the possibility to delay the decision on palovarotene. Currently there are no FDA-approved products for this indication.

12/29/2022: mosunetuzumab
The FDA has granted priority review of Genentech (Roche)’s mosunetuzumab for treatment of adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies. FL is the most common indolent (slow growing) form of non-Hodgkin’s lymphoma (NHL), a type of blood cancer, which often returns after initial therapy. Mosunetuzumab is a potential first-in-class CD20xCD3 T-cell engaging bispecific antibody. The BLA is based on positive results from the pivotal Phase 1/2 GO29781 study, which demonstrated high complete response (CR) rates, with 57% responders maintaining responses for at least 18 months, and manageable tolerability in people with heavily pretreated FL. After a median follow-up of 18.3 months, the CR rate was 60% and the ORR was 80%. The median duration of response among those who responded was 22.8 months.⁶ Similar products include Novartis’ Kymriah^® (tisagenlecleucel) and Kite Pharma’s Yescarta^® (axicabtagene ciloleucel).

1. https://www.pharmacytimes.com/view/oncology-overview-adagrasib-mrtx849-for-non-small-cell-lung-cancer
2. https://www.onclive.com/view/fda-accepts-bla-resubmission-for-toripalimab-in-advanced-nasopharyngeal-carcinoma
3. https://www.pharmacytimes.com/view/gilead-resubmits-nda-for-lenacapavir-updates-based-on-fda-complete-response-letter
4. https://www.pharmacytimes.com/view/tg-therapeutics-ublituximab-shows-reduced-risk-of-relapsing-forms-of-multiple-sclerosis
5. https://www.ipsen.com/press-releases/ipsen-announces-u-s-fda-priority-review-for-palovarotene-new-drug-application-in-patients-with-fibrodysplasia-ossificans-progressiva-following-resubmission/
6. https://www.onclive.com/view/fda-grants-priority-review-to-mosunetuzumab-for-relapsed-refractory-follicular-lymphoma

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

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.pharmacytimes.com/view/oncology-overview-adagrasib-mrtx849-for-non-small-cell-lung-cancer
2. https://www.onclive.com/view/fda-accepts-bla-resubmission-for-toripalimab-in-advanced-nasopharyngeal-carcinoma
3. https://www.pharmacytimes.com/view/gilead-resubmits-nda-for-lenacapavir-updates-based-on-fda-complete-response-letter
4. https://www.pharmacytimes.com/view/tg-therapeutics-ublituximab-shows-reduced-risk-of-relapsing-forms-of-multiple-sclerosis
5. https://www.ipsen.com/press-releases/ipsen-announces-u-s-fda-priority-review-for-palovarotene-new-drug-application-in-patients-with-fibrodysplasia-ossificans-progressiva-following-resubmission/
6. https://www.onclive.com/view/fda-grants-priority-review-to-mosunetuzumab-for-relapsed-refractory-follicular-lymphoma