▎ WuXi AppTec content team editor
In April, according to the PDUFA schedule, the FDA is likely to make a review decision on four new drugs in the next 3 weeks, two of which are from China, as detailed in the table below.
▲ New drugs that are expected to be approved in the United States in the next 3 weeks (WuXi AppTec content team mapping, click to see the larger picture, * parentheses in the company merged product development companies)
1. New drug name: mavacamten
Company Name: Bristol-Myers Squibb
Indications: Obstructive hypertrophic cardiomyopathy
Bristol Squibb's mavacamten is an oral myocardial myoglobulin inhibitor obtained by the company through its acquisition of MyoKardia in November 2020 for oral treatment of obstructive hypertrophic cardiomyopathy (oHCM). The NDA submitted by Mavacamten in March 2021 was received by the FDA based on positive Phase 3 clinical results, which showed that both primary and secondary efficacy endpoints were met and that the safety was similar to that of placebo. If FDA approval is obtained by the PDUFA date of April 28, 2022, it could become a potential "first-in-class" drug against the oHCM disease mechanism. In addition to listing applications in the United States, mavacamten also has a Marketing Authorisation Application (MAA) under review in the European Union for the same indications. Currently, the company is conducting clinical trials to evaluate mavacamten's potential ability to treat other indications, including non-obstructive hypertrophic cardiomyopathy.
2. New drug name: AXS-07
Company name: Axsome Therapeutics
Indications: Migraine
Focused on the treatment of central nervous system disorders, Axsome is developing AXS-07, a novel, rapidly absorbing combination of oral fixed doses with the active ingredients meloxicam and rizatriptan, and using Axsome's MoSEIC formulation technology for the acute treatment of migraines. Positive results from two Phase 3 trials showed rapid and sustained efficacy compared with placebo and active control rizatriptan. The FDA received the NDA of Axsome to AXS-07 in September 2021, setting the PDUFA target date to April 30, 2022. If approved, the combination will provide a multi-mechanism approach to treating migraines.
3. New drug name: Sulvatinib
Company Name: Hehuang Pharmaceutical
Indications: Pancreatic and non-pancreatic neuroendocrine tumors
Hehuang Medicine's suvaftinib is an oral tyrosine kinase inhibitor with dual activity of anti-angiogenesis and immunomodulatory for the treatment of pancreatic and non-pancreatic neuroendocrine tumors (NET). Based on positive Phase 3 results, Surufatinib's NDA application was accepted by the FDA in June 2021, and the results showed that the drug had reached the primary efficacy endpoint. The FDA has set the PDUFA target date to April 30, 2022. The drug is already available in China and is also seeking approval from the European Union. If approved in the U.S. under current plans, the company expects the drug to be available in the second half of 2022, providing additional treatment options for patients with advanced NET.
4. New drug name: Triprilimab (toripalimab)
Company Name: Coherus BioSciences
Indications: Nasopharyngeal carcinoma
Toripalimab, jointly developed by Junshi Bio and CoherusBioSciences, is an anti-PD-1 monoclonal antibody used to treat recurrent or metastatic nasopharyngeal carcinoma. In November 2021, the FDA received a Biological Product Licensing Application (BLA) from Toripalimab, supported by positive safety and efficacy results from Phase 2 and Phase 3 studies, and was granted priority review qualification. The PDUFA date is April 30, 2022. Triprilizumab has been approved for marketing in China for the treatment of non-resectable or metastatic melanoma. If approved by the FDA, treprilizumab combined with chemotherapy could become the new standard for first-line treatment for advanced nasopharyngeal cancer. For advanced nasopharyngeal cancer, there is currently no FDA-approved immuno-oncology therapy.
Expected US New Drug Approvals in April 2022
In April, the FDA’s schedule remains busy,with a potential of four drugs to be approved within the month.
（By WuXi AppTec content team. Click the image to view at full size）
1. Drug: mavacamten
Company: Bristol Myers Squibb
Indication(s): Symptomatic obstructive hypertrophic cardiomyopathy
Bristol Myers Squibb’s mavacamten is an oral cardiac myosin inhibitor gained by the company via acquisition of MyoKardia in November 2020, for the potential oral treatment of symptomatic obstructive hypertrophic cardiomyopathy. Mavacamten’s NDA submission in March 2021 was accepted by the FDA based on positive phase III results which demonstrated that both the primary and secondary efficacy endpoints were met and the safety profile was similar to that of placebo. If approved by the FDA by the PDUFA date of April 28, 2022, it could become a first-in-class medicine targeting the underlying disease of symptomatic obstructive hypertrophic cardiomyopathy, a cardiovascular disease with serious unmet need. Other than the marketing application in the US, mavacamten also has a MAA under review in the EU for the same indication. Clinical trials are ongoing to evaluate the potential ability of mavacamten to treat additional indications including non-obstructive hypertrophic cardiomyopathy.
2. Drug: meloxicam + rizatriptan fixed dose combination (AXS-07)
Company: Axsome Therapeutics
Indication(s): Migraine
With a focus on therapies for the management of central nervous system disorders, Axsome is developing AXS-07, a novel, rapidly absorbed, oral fixed-dose combination of the non-steroidal anti-inflammatory COX2 inhibitor meloxicam and the 5-HT1B/D agonist rizatriptan, formulated using the company’s MoSEIC technology, for the acute treatment of migraine. The FDA accepted Axsome’s NDA for AXS-07 in September 2021, based on positive results from two phase III trials which showed rapid and sustained efficacy of the combination compared with placebo and the active comparator rizatriptan. The FDA has set the PDUFA target action date for April 30, 2022.If approved, the combination would provide a multi-mechanistic approach to treating migraine.
3. Drug: surufatinib
Company: Hutchison China Meditech (HUTCHMED)
Indication(s): Pancreatic and non-pancreatic neuroendocrine tumors
Another therapeutic which is seeking FDA approval is HUTCHMED’s surufatinib, a small molecule inhibitor of VEGFR and FGFR1 and CSF-1R tyrosine kinases, for the treatment of pancreatic and extra-pancreatic neuroendocrine tumors (NETs). Surufatinib’s NDA filing was accepted by the FDA in June 2021, based on positive phase III results which showed the drug to have met primary efficacy endpoint and was safe. The FDA has set a PDUFA target date as April 30, 2022.HUTCHMEDhas an ongoing expanded access program in the US with surufatinib for patients with limited treatment options for neuroendocrine tumor. According to the company’s recent announcement, clinical site inspections and pre-approval inspections of manufacturing facilities are in progress, with several already completed. Mid- and late-cycle review meetings with the FDA have also been completed. The drug is already available in China and is also seeking approval in the EU. If approved in the US under the current plan, the company anticipated launch by H2 2022 to provide additional treatment option for advanced NET patients.
4. Drug: toripalimab
Company: Junshi Biosciences/Coherus BioSciences
Indication(s): Nasopharyngeal carcinoma
Toripalimab is an anti-PD-1 monoclonal antibody being developed by Junshi and licensee Coherus, for the potential treatment of recurrent or metastatic nasopharyngeal carcinoma. In November 2021, the FDA accepted the toripalimab BLA, which is supported by positive safety and efficacy results from a phase II and a phase III studies and granted the BLA priority review,with a target action date of April 2022.Toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing in China to treat unresectable or metastatic melanoma. If approved by the FDA, toripalimab, in combination with chemotherapy, could become the new standard of care for first-line treatment of advanced nasopharyngeal carcinoma, an aggressive tumor that currently has no FDA-approved immuno-oncology treatment.
Resources:
[1] Bristol Myers Squibb - U.S. Food and Drug Administration Approves First LAG-3-Blocking Antibody Combination, Opdualag (nivolumab and relatlimab-rmbw), as Treatment for Patients with Unresectable or Metastatic Melanoma. Retrieved March 28, 2022 from,https://news.bms.com/news/corporate-financial/2022/U.S.-Food-and-Drug-Administration-Approves-First-LAG-3-Blocking-Antibody-Combination-Opdualag-nivolumab-and-relatlimab-rmbw-as-Treatment-for-Patients-with-Unresectable-or-Metastatic-Melanoma/default.aspx
[2] Marinus Pharmaceuticals, Inc. - Marinus Pharmaceuticals Announces FDA Approval of ZTALMY (ganaxolone) for CDKL5 Deficiency Disorder. Retrieved March 28, 2022 from,https://ir.marinuspharma.com/news/news-details/2022/Marinus-Pharmaceuticals-Announces-FDA-Approval-of-ZTALMY-ganaxolone-for-CDKL5-Deficiency-Disorder/default.aspx
[3] BioXcel Therapeutics Reports Fourth Quarter and Full Year 2021 Financial Results and Recent Operational Highlights. Retrieved March 28, 2022 from, https://ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-reports-fourth-quarter-and-full-year-2021
[4] BioXcel Therapeutics Announces Journal of the American Medical Association Publication of Data from SERENITY II Pivotal Phase 3 Trial Evaluating BXCL501 in Bipolar Disorders. Retrieved March 28, 2022 from,https://ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-announces-journal-american-medical
[5] Vutrisiran factsheet. Retrieved March 28, 2022 from,https://www.alnylam.com/wp-content/uploads/pdfs/Vutrisiran-Fact-Sheet.pdf
[6] Alnylam Announces U.S. Food and Drug Administration Acceptance of New Drug Application for Investigational Vutrisiran for the Treatment of the Polyneuropathy of Hereditary ATTR Amyloidosis. Retrieved March 28, 2022 from,https://investors.alnylam.com/press-release?id=25811
[7] Fourth Quarter and Full Year 2021 Financial Results presentation - Alnylam. Retrieved March 28, 2022 from,https://alnylampharmaceuticalsinc.gcs-web.com/static-files/a66094b4-18cb-4d0e-9832-18e62e242f97
[8] Bristol Myers Squibb Completes Acquisition of MyoKardia, Strengthening Company’s Leading Cardiovascular Franchise. Retrieved March 28, 2022 from,https://news.bms.com/news/details/2020/Bristol-Myers-Squibb-Completes-Acquisition-of-MyoKardia-Strengthening-Companys-Leading-Cardiovascular-Franchise/default.aspx
[9] U.S. Food and Drug Administration (FDA) Accepts Bristol Myers Squibb’s Application for Mavacamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM). Retrieved March 28, 2022 from,https://news.bms.com/news/corporate-financial/2021/U.S.-Food-and-Drug-Administration-FDA-Accepts-Bristol-Myers-Squibbs-Application-for-Mavacamten-in-Symptomatic-Obstructive-Hypertrophic-Cardiomyopathy-oHCM/default.aspx
[10] Efficacy and Safety of Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy: Results of the EXPLORER-HCM Study. Retrieved March 28, 2022 from,https://www.ajmc.com/view/adults-with-symptomatic-obstructive-hypertrophic-cardiomyopathy-results-of-the-explorer-hcm-study
[12] A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed MAVERICK-HCM or EXPLORER-HCM. Retrieved March 28, 2022 from,https://www.clinicaltrials.gov/ct2/show/NCT03723655?term=Mavacamten&draw=2&rank=7
[13] A Study of Mavacamten in Participants With HFpEF and Elevation of NT-proBNP With or Without Elevation of cTnT (EMBARK-HFpEF). Retrieved March 28, 2022 from,https://www.clinicaltrials.gov/ct2/show/NCT04766892?term=Mavacamten&draw=2&rank=3
[14] European Medicines Agency Validates Bristol Myers Squibb’s Application for Mavacamten for the Treatment of Obstructive Hypertrophic Cardiomyopathy. Retrieved March 28, 2022 from,https://news.bms.com/news/details/2021/European-Medicines-Agency-Validates-Bristol-Myers-Squibbs-Application-for-Mavacamten-for-the-Treatment-of-Obstructive-Hypertrophic-Cardiomyopathy/default.aspx
[15] Corporate Presentation January 2022 - Axsome Therapeutics. Retrieved March 28, 2022 from,https://axsometherapeuticsinc.gcs-web.com/static-files/d0beb034-c48d-45c2-8ac3-bfd85f26177f
[16] Axsome Therapeutics Announces FDA Acceptance of New Drug Application for AXS-07 for the Acute Treatment of Migraine. Retrieved March 28, 2022 from,https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-fda-acceptance-new-drug-0
[17] Axsome Therapeutics Reports Fourth Quarter and Full Year 2021 Financial Results and Provides Business Update. Retrieved March 28, 2022 from,https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-reports-fourth-quarter-and-full-year-2021
[18] Evaluation of surufatinib, an orally available VEGFR, FGFR1 and CSF-1R inhibitor, in combination with immune checkpoint blockade or chemotherapy in preclinical tumor models. Retrieved March 28, 2022 from,https://www.ejcancer.com/article/S0959-8049(20)31132-1/fulltext
[19] HUTCHMED Reports 2021 Full Year Results and Provides Business Updates. Retrieved March 28, 2022 from,https://www.hutch-med.com/fy2021-results/#_edn3
[20] U.S. FDA Accepts Filing of HUTCHMED’s NDA for Surufatinib for the Treatment of Advanced Neuroendocrine Tumors. Retrieved March 28, 2022 from,https://www.hutch-med.com/fda-accepts-surufatinib-nda-for-net/
[21] Expanded Access Program of Surufatinib. Retrieved March 28, 2022 from,https://www.clinicaltrials.gov/ct2/show/NCT04814732
[22] US FDA Accepted BLA Filing for Toripalimab for Treatment of NPC. Retrieved March 28, 2022 from,https://www.junshipharma.com/en/News.html
[23] Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02). Retrieved March 28, 2022 from,https://ascopubs.org/doi/full/10.1200/JCO.20.02712