Davy James

The FDA has approved Accord BioPharma's 420 mg strength Hercessi (trastuzumab-strf), a biosimilar to Herceptin, for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast and gastric cancers.

 The regulatory action follows the April 2024 FDA approval of 150 mg strength Hercessi for the same indication.

The biosimilar now has approved indications for HER2-overexpressing breast cancer, HER2-overexpressing metastatic breast cancer (mBC), and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.

"At Accord BioPharma, we are deeply committed to helping patients gain access to the medicines they need, and we will continue our efforts to help all stakeholders recognize the promise of biosimilars," Chrys Kokino, US president of Accord, said in a press release. "Although each cancer patient is unique, the cost of oncologic therapies often adds a significant burden on top of other existing challenges. We strive to respond to those needs with biosimilars like Hercessi."

The approval was based on findings from three studies that provided comprehensive analytical, preclinical, and clinical data, demonstrating equivalence between Hercessi and reference Herceptin in terms of efficacy, safety, and quality, according to Accord. These included a pair of Phase I comparative single-dose pharmacokinetic (PK) studies conducted in healthy participants—HLX02-HV01 and HLX02-HV02—as well as the supportive double-blind, randomized HLX02-BC01 Phase III trial. HLX02-BC01 analyzed efficacy and safety comparability data among patients with HER2-overexpressing mBC in combination with docetaxel. Investigators found that the PK comparability and clinical efficacy and safety data shown in the HLX02-HV02 and HLX02-BC01 trials adhere to the current biosimilar guidance from the FDA.

In terms of safety, the profile of Hercessi was consistent with the known safety profile of reference Herceptin. Data show no clinically meaningful differences between the biosimilar and reference product, which supports the biosimilarity between the two drugs, according to Accord.

Hercessi was originally developed by Shanghai Henlius Biotech, with exclusive rights to develop and commercialize the drug in the United States and Canada granted to Accord in 2021.

"The strength and success of our collaboration with Accord continues with the approval of the 420mg strength of Hercessi,” said Dr. Jason Zhu, executive director and CEO of Henlius in a press release. “This represents an important step in our journey to meet the needs of patients with innovative, high quality, and affordable therapeutics."

The impact of approved biosimilars on drug pricing has been significant. A study released last year by the University of Southern California’s Leonard D. Schaeffer Center for Health Policy & Economics and published in 

 compared trastuzumab to five biosimilar entrants. Investigators found that the reference trastuzumab began losing market share immediately after the biosimilar Kanjinti (trastuzumab-anns; Amgen) launched, and continues to lose market share to the other approved biosimilars.

“With multiple biosimilar competitors entering the US market quickly, trastuzumab is the best example to date of biosimilars fulfilling their promise to reduce biologic drug prices,” said Alice Chen, PhD, associate professor and vice dean for research at the Sol Price School of Public Policy at the University of Southern California, in a press release. “In just three years, the trastuzumab market displayed important hallmarks of competition: doctors could choose among six products; new entrants rapidly captured market share from the originator; and prices steadily declined on all six options. Prices of some versions declined by more than half, and the originator lost half of the market.”

1. Accord BioPharma, Inc. Announces U.S. Food & Drug Administration Approval of 420mg Strength of HERCESSI™ (trastuzumab-strf), a biosimilar to Herceptin® (trastuzumab), for the Treatment of Several Forms of HER2-Overexpressing Cancer. News release. Accord BioPharma. September 18, 2024. Accessed September 18, 2024. 

https://prnmedia.prnewswire.com/news-releases/accord-biopharma-inc-announces-us-food--drug-administration-approval-of-420mg-strength-of-hercessi-trastuzumab-strf-a-biosimilar-to-herceptin-trastuzumab-for-the-treatment-of-several-forms-of-her2-overexpressing-cance-302251163.html

2. Accord BioPharma, Inc. Announces U.S. Food & Drug Administration Approval of HERCESSI™ (trastuzumab-strf), a biosimilar to Herceptin® (trastuzumab) for the Treatment of Several Forms of HER2-Overexpressing Cancer. PR Newswire. April 29, 2024. Accessed September 18, 2024. 

https://www.prnewswire.com/news-releases/accord-biopharma-inc-announces-us-food--drug-administration-approval-of-hercessi-trastuzumab-strf-a-biosimilar-to-herceptin-trastuzumab-for-the-treatment-of-several-forms-of-her2-overexpressing-cancer-302129508.html

3. Accord BioPharma Announces U.S. FDA Acceptance of Biologics License Application for Proposed Biosimilar Trastuzumab HLX02. PR Newswire. April 5, 2023. Accessed September 18, 2024. 

https://www.prnewswire.com/news-releases/accord-biopharma-announces-us-fda-acceptance-of-biologics-license-application-for-proposed-biosimilar-trastuzumab-hlx02-301790459.html

4. Biosimilars drug market isn’t broken after all, USC Schaeffer study finds. News release. EurekAlert. June 6, 2023. Accessed September 18, 2024. 

https://www.eurekalert.org/news-releases/991617

Articles

Accord BioPharma's 420 mg strength Hercessi (trastuzumab-strf), a biosimilar to Herceptin, gains FDA approval to treat HER2-overexpressing breast cancer and gastric cancer.

FDA Approves New Dose Strength of Herceptin Biosimilar for HER2-Overexpressing Breast, Gastric Cancers

The FDA has granted Fast Track designation to Sun Pharma and Moebius Medical’s MM-II treatment for osteoarthritis (OA) knee pain, with Phase III clinical trials planned to expedite a potential approval. The non-opioid product uses proprietary suspension of liposomes to provide relief for joint pain in the treatment of osteoarthritis (OA).

“As we enter Phase III development, we are very encouraged by the FDA’s decision to grant Fast Track designation to MM-II and recognize its potential to fill an unmet medical need for patients suffering from Osteoarthritis,” Marek Honczarenko, MD, PHD, senior vice president, head of Global Development for Sun Pharma, said in a press release.

The novel, non-opioid MM-II uses a proprietary suspension of large, empty, multilamellar liposomes intended to lower friction on the joint, thereby providing relief for pain associated with OA. Findings from a Phase IIb clinical trial (NCT04506463)

 presented at the European Alliance of Associations for Rheumatology 2024 showed the efficacy of MM-II in patients with OA. The randomized, controlled, clinical trial demonstrated that a single intra-articular injection of 3 mL of MM-II produced favorable pain relief in comparison with a placebo for up to 26 weeks. Results from the trial show that patients achieved a greater than 50% improvement in knee pain from weeks 12 to 26 following treatment with MM-II.

"Given the limitations of many current therapies, there is an urgent need for more therapeutic treatment options for patients with painful osteoarthritis,” said Philip G. Conaghan, professor of Musculoskeletal Medicine at the University of Leeds and Director of the NIHR Leeds Biomedical Research Centre, in a press release. “Data from the 3mL dose of MM-II in this trial demonstrate MM-II's potential to offer durable and meaningful pain relief with good tolerability."

These data supported the Fast Track designation from the FDA, which will expedite the development and review of the treatment, which may be eligible for the FDA’s accelerated approval process.

"With over 100 million people currently suffering from joint pain, there is a significant unmet need for additional OA therapies,” said Abhay Gandhi, CEO, North America Business, Sun Pharma, in a press release. “This analysis from our clinical trial is further confirmation of the potential role that MM-II will be able to play in improving painful OA treatment."

OA is a common degenerative joint disease that particularly impacts the knee and is characterized by cartilage wear, pain, and motion limitations. There is currently no cure available for OA, as current treatments seek to relieve pain and improve joint function. The condition affects more than 100 million people worldwide and is a leading cause of disability.

“This Fast Track Designation, which will enable FDA to review MM-II in an expedited manner, is an important milestone in the development of MM-II, and follows our recently released Phase IIb data, which showed MMII’s potential to provide effective and durable treatment for patients with knee pain of osteoarthritis,” said Moshe Weinstein, CEO, Moebius Medical, in a press release.

1. Sun Pharma, Moebius Medical. Sun Pharma and Moebius Medical announce fast track designation granted for MM-II for the treatment of osteoarthritis knee pain. News Release. Released September 6, 2024. Accessed September 17, 2024. https://sunpharma.com/wp-content/uploads/2024/09/Press-Release-Sun-Pharma-and-Moebius-Medical-Announce-Fast-Track-Designation-Granted-for-MM-II.pdf

2. Efficacy and safety of MM-II for treatment of knee pain in subjects With symptomatic knee osteoarthritis. ClinicalTrials.gov. National Library of Medicine. August 29, 2024. Accessed September 17, 2024. https://clinicaltrials.gov/study/NCT04506463

3. Oral presentation at EULAR 2024 of data from global phase 2b clinical trial demonstrates durability of pain relief after a single injection of MM-II in patients with painful knee osteoarthritis (OA). News Release. Moebius. June 14, 2024. Accessed September 17, 2024. https://www.prnewswire.com/il/news-releases/oral-presentation-at-eular-2024-of-data-from-global-phase-2b-clinical-trial-demonstrates-durability-of-pain-relief-after-a-single-injection-of-mm-ii-in-patients-with-painful-knee-osteoarthritis-oa-302172939.html

FDA fast tracks Sun Pharma and Moebius Medical’s MM-II treatment for osteoarthritis knee pain, with Phase III clinical trials planned to expedite a potential approval.

FDA Grants Fast Track Designation to Non-Opioid Treatment for Osteoarthritis Knee Pain

Image credit: Bernard Chantal | stock.adobe.com

Merck’s novel adult-specific 21-valent pneumococcal conjugate vaccine V116 demonstrated positive results in multiple clinical trials across all 21 serotypes covered by the vaccine, according to data presented at the 13th Meeting of the International Society of Pneumonia and Pneumococcal Diseases.

 V116 includes eight serotypes that are not addressed by currently approved pneumococcal vaccines, including 15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B. Those serotypes were responsible for approximately 30% of invasive pneumococcal disease in individuals aged 65 years and older.

Pre-pandemic 2019 data from the CDC indicate that the 21 serotypes covered by the V116 vaccine are responsible for 85% of invasive pneumococcal disease in adults 65 years of age and older.

“Invasive pneumococcal disease and pneumococcal pneumonia can cause serious illness, especially in older adults and those with immunocompromising conditions,” Walter Orenstein, MD, professor emeritus of medicine, epidemiology, global health and pediatrics at Emory University and member of Merck’s Scientific Advisory Committee, said in a press release. “These positive data demonstrate the potential for V116 to address an unmet need in adult pneumococcal disease prevention.”

There are more than 100 different serotypes of pneumococcal bacteria that may affect adults differently than children.

 Those with a greater risk of infection include older adults and patients with certain chronic or immunocompromising health conditions, such as heart disease, lung disease, and liver disease. Mortality from invasive pneumococcal disease is highest among those aged 50 years and older.

The positive results from these Phase III clinical trials include the pivotal STRIDE-3 (

Investigators found that V116 was immunogenic for all 21 serotypes covered by the vaccine across several adult populations, including individuals who were pneumococcal vaccine-naïve, individuals who were pneumococcal vaccine-experienced, and individuals with an elevated risk of pneumococcal disease, including patients with HIV. Further, V116 produced greater immune responses than the comparators evaluated in the STRIDE trials for the serotypes unique to V116.

Among pneumococcal vaccine-naïve individuals aged 50 years and older in a subgroup of STRIDE-3, the vaccine was immunogenic across all 21 serotypes in the age groups of 50–64 years, 65–74 years, and 75–84 years.

Among pneumococcal vaccine-experienced adults aged 50 years and older in the STRIDE-6 trial, V116 produced immune responses that were comparable for the serotypes shared with the pneumococcal 15-valent conjugate vaccine (PCV15) and pneumococcal vaccine, polyvalent (23-valent [PPSV23]), as well as greater immune responses for the serotypes covered by V116 only, regardless of prior administration of a pneumococcal vaccine or the duration since it was administered.

In the STRIDE-7 trial, patients with HIV aged 18 years and older administered V116 experienced immune responses that were comparable to PCV15 and PPSV23 across all 13 shared serotypes, as well as greater immune responses for the eight serotypes covered by V116 only. In terms of safety, V116 showed a profile that was comparable to the studied comparative vaccines, including the pneumococcal 20-valent conjugate vaccine, PCV15, and PPSV23.

 to a biologics license application for V116, as a single dose for the prevention of invasive pneumococcal disease and pneumococcal pneumonia in adults. The BLA was given a Prescription Drug User Fee Act (PDUFA) date of June 17, 2024.

“The extensive data presented this week reaffirm our confidence in the potential clinical value V116 could provide to a range of adult populations,” Eliav Barr, MD, Merck Research Laboratories senior vice president, head of global clinical development, and chief medical officer, said in a press release. “We are encouraged by the results of these studies showing that V116 has generated immune responses to the serotypes responsible for the majority of adult invasive pneumococcal disease.”

1. Merck Announces Positive Data on V116, an Investigational, 21-Valent Pneumococcal Conjugate Vaccine Specifically Designed for Adults, Demonstrated Immune Responses in Adults. Merck. News release. March 19, 2024. Accessed March 19, 2024. 

https://www.merck.com/news/merck-announces-positive-data-on-v116-an-investigational-21-valent-pneumococcal-conjugate-vaccine-specifically-designed-for-adults-demonstrated-immune-responses-in-adults/

2. FDA Grants Priority Review to Merck’s New Biologics License Application for V116, an Investigational, 21-valent Pneumococcal Conjugate Vaccine Specifically Designed to Protect Adults. Merck. News release. December 19, 2023. Accessed March 19, 2024. 

https://www.merck.com/news/fda-grants-priority-review-to-mercks-new-biologics-license-application-for-v116-an-investigational-21-valent-pneumococcal-conjugate-vaccine-specifically-designed-to-protect-adults/

The FDA previously granted priority review to a biologics license application for V116 as a single dose for the prevention of invasive pneumococcal disease and pneumococcal pneumonia in adults.

Merck's 21-Valent Pneumococcal Conjugate Vaccine Shows Efficacy Across Various Serotypes

Image credit: TuMeggy | stock.adobe.com. 

The FDA has approved Allecra Therapeutics’ Exblifep (cefepime/enmetazobactam) for the treatment of complicated urinary tract infections (cUTIs), including the kidney infection pyelonephritis, in patients aged 18 years and older.

 The FDA also granted Allecra with a five-year marketing exclusivity extension for the β-lactam/β-lactamase inhibitor combination through the Generating Antibiotic Incentives Now Act (GAIN Act), which is legislation that incentivizes the development of new anti-infective treatments.

"Receiving FDA approval is a tremendous achievement for Allecra and a testament to the hard work and dedication of a small, yet highly focused team of individuals. I extend my sincere congratulations to my colleagues Omar Lahlou and Patrick Velicitat for their leadership and oversight throughout this whole process,” Iain Buchanan, supervisory board member of Allecra Therapeutics, said in a press release. “As we continue our discussions with strategic partners for product launch in the US, we value the FDA’s positive decision on Exblifep’s ability to address a critical unmet medical need for patients.”

The efficacy of Exblifep was evaluated in the randomized, controlled, double-blind, global Phase III ALLIUM trial, which compared the treatment with the current standard of care of piperacillin/tazobactam. Exblifep achieved the trial’s primary outcome of clinical cure and microbiological eradication for non-inferiority and superiority compared with piperacillin/tazobactam.

The trial enrolled 1,041 patients, 18 years of age and above, with a clinical diagnosis of cUTI or acute pyelonephritis caused by gram-negative urinary pathogens. Patients were randomly assigned to receive either 2 g cefepime/0.5 g enmetazobactam or 4 g piperacillin/0.5 g tazobactam by two-hour infusion every eight hours for seven days.

The results showed that 79.1% of patients administered Exblifep achieved the primary outcome vs. 58.9% of those administered piperacillin/tazobactam. Treatment-emergent adverse events were observed in 50.0% of patients administered Exblifep compared with 44.0% with piperacillin/tazobactam.

“Among patients with complicated UTI or acute pyelonephritis caused by gram-negative pathogens, [Exblifep], compared with piperacillin/tazobactam, met criteria for noninferiority as well as superiority with respect to the primary outcome of clinical cure and microbiological eradication,” the study authors wrote. “Further research is needed to determine the potential role for [Exblifep] in the treatment of complicated UTI and pyelonephritis.”

According to the study investigators, increasing resistance rates have reduced the clinical utility of commonly used UTI treatments, including aminoglycosides, fluoroquinolones, and β-lactams.With rates of extended-spectrum β-lactamases on the rise, the investigators noted that the use of carbapenems for the treatment of these infections has increased resistance, which emphasizes the importance of developing new treatments.

“Antimicrobial resistance mediated by ESBLs is a critical clinical challenge and there is a substantial need for novel antibiotics that enable us to effectively treat resistant infections,” said lead study author Keith Kaye MD, MPH, chief, Division of Allergy, Immunology and Infectious Diseases at the Robert Wood Johnson Medical School (Rutgers University), in a press release. “[Exblifep] has shown improved efficacy compared to a standard of care treatment with a good safety profile. It has the potential to become a replacement for piperacillin/tazobactam and an alternative to the use of carbapenems.”

1. Allecra Therapeutics Announces U.S. FDA Approval for EXBLIFEP® for the Treatment of Complicated Urinary Tract Infections. Allecra Therapeutics. News release. February 27, 2024. Accessed February 27, 2024. 

https://www.businesswire.com/news/home/20240227132611/en/Allecra-Therapeutics-Announces-U.S.-FDA-Approval-for-EXBLIFEP%C2%AE-for-the-Treatment-of-Complicated-Urinary-Tract-Infections

2. Kaye KS, Belley A, Barth P, et al. Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis: A Randomized Clinical Trial. 

 2022;328(13):1304–1314. doi:10.1001/jama.2022.17034

3. Allecra Therapeutics Publishes Final Phase 3 ALLIUM Data in JAMA: Cefepime/Enmetazobactam Met Criteria for Superiority. News release. October 5, 2022. Accessed February 27, 2024. 

https://www.biospace.com/article/releases/allecra-therapeutics-publishes-final-phase-3-allium-data-in-jama-cefepime-enmetazobactam-met-criteria-for-superiority/?keywords=Allecra

Compared with piperacillin/tazobactam, Exblifep (cefepime/enmetazobactam) showed noninferiority and superiority in a clinical cure and microbiological eradication of complicated urinary tract infections.