On September 18, 2024 Accord BioPharma, Inc., the U.S. specialty division of Intas Pharmaceuticals, Ltd., focused on the development of oncology, immunology, and critical care therapies, reported that the U.S. Food and Drug Administration (FDA) has approved a 420mg strength of HERCESSI (trastuzumab-strf), a biosimilar to Herceptin (trastuzumab), to treat HER2-overexpressing breast and gastric or gastroesophageal junction adenocarcinoma (Press release, Accord BioPharma, SEP 18, 2024, View Source;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 [SID1234646726]). This milestone, together with FDA approval of a 150mg strength of HERCESSI earlier this year, paves the way for the company to commercially launch its first biosimilar in the U.S. in early 2025.

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"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," said Chrys Kokino, U.S. president of Accord. "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."

HERCESSI is indicated for the adjuvant treatment of adult patients with HER2-overexpressing breast cancer, the treatment of HER2-overexpressing metastatic breast cancer, and the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. In general, HER2 cancers are particularly aggressive and respond well to targeted treatment. HERCESSI works by binding to and inactivating the HER2 receptor, slowing down cell replication.

FDA approval was granted based on a comprehensive package of analytical, preclinical, and clinical data, collected in three studies, which showed HERCESSI and its reference product, Herceptin (trastuzumab) are similar in terms of efficacy, safety, and quality. The studies included two Phase 1 comparative single-dose pharmacokinetic (PK) studies conducted in healthy volunteers (HLX02-HV01 and HLX02-HV02), and a supportive Phase 3, double-blind, randomized clinical efficacy and safety compafrability study in patients with HER2-overexpressing metastatic breast cancer in combination with docetaxel (HLX02-BC01). The PK comparability and clinical efficacy/safety similarity exercised in HLX02-HV02 and HLX02-BC01 adheres to current biosimilar guidance from the FDA.

The safety profile of HERCESSI has been shown to be consistent with the safety profile for the reference product Herceptin. The data demonstrate that there are no clinically meaningful differences between HERCESSI and Herceptin in the populations studied and support biosimilarity between the two therapies.

"Our organization has long been at the forefront of the biosimilar industry, bringing treatments to regulated markets such as the EU. The FDA’s approval of both strengths of HERCESSI marks the beginning of Accord BioPharma’s journey to bring a portfolio of biosimilars to the U.S. that can help achieve significant savings," said Binish Chudgar, vice chairman and managing director, Intas Pharmaceuticals. "The vast global biosimilars experience within our organization, combined with the passion and drive of our employees, has helped us achieve this important milestone, which will expand the range of affordable treatment options for breast and gastric cancer patients."

HERCESSI was originally developed by Accord’s business partner Shanghai Henlius Biotech, Inc. headquartered in Shanghai, China. In 2021, Henlius granted Accord BioPharma the exclusive rights to develop and commercialize HERCESSI in the U.S. and Canada.

Dr. Jason Zhu, executive director and chief executive officer of Henlius remarked, "The strength and success of our collaboration with Accord continues with the approval of the 420mg strength of HERCESSI. This represents an important step in our journey to meet the needs of patients with innovative, high quality, and affordable therapeutics."

HERCESSI was originally approved by the FDA at a dosage of 150mg on April 25, 2024, and is the first U.S. FDA-approved biosimilar from Accord BioPharma, which has also submitted a Biologics License Application to the FDA for biosimilar versions of pegfilgrastim, filgrastim, and ustekinumab. Accord BioPharma is planning on introducing several additional biosimilars to the U.S. market during the next five years.

HERCESSI (trastuzumab-strf) for injection, for intravenous use.

HERCESSI (trastuzumab-strf) is biosimilar to HERCEPTIN (trastuzumab).

Boxed Warning and Additional Important Safety Information
WARNING: CARDIOMYOPATHY, INFUSION REACTIONS, EMBRYO-FETAL TOXICITY, and PULMONARY TOXICITY
See full prescribing information for complete boxed warning.

Cardiomyopathy: Trastuzumab products can result in subclinical and clinical cardiac failure manifesting as CHF, and decreased LVEF, with greatest risk when administered concurrently with anthracyclines. Evaluate cardiac function prior to and during treatment. Discontinue HERCESSI for cardiomyopathy.

Infusion Reactions, Pulmonary Toxicity: Discontinue HERCESSI for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.

Embryo-Fetal Toxicity: Exposure to trastuzumab products during pregnancy can result in oligohydramnios, in some cases complicated by pulmonary hypoplasia and neonatal death. Advise patients of these risks and the need for effective contraception.

Cardiomyopathy

Trastuzumab products can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving trastuzumab with anthracycline-containing chemotherapy regimens.
Trastuzumab products can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death.
Trastuzumab products can also cause asymptomatic decline in left ventricular ejection fraction (LVEF).
Discontinue HERCESSI treatment in patients receiving adjuvant therapy and withhold HERCESSI in patients with metastatic disease for clinically significant decrease in left ventricular function.
Cardiac Monitoring

Evaluate left ventricular function by echocardiogram or MUGA scan in all patients prior to and every 3 months during treatment with HERCESSI, and every 6 months for at least 2 years following completion of HERCESSI as a component of adjuvant therapy.
Repeat LVEF measurement at 4 week intervals if Hercessi is withheld for significant left ventricular cardiac dysfunction.
The safety of continuation or resumption of HERCESSI in patients with trastuzumab product-induced left ventricular cardiac dysfunction has not been studied.
Infusion Reactions

With trastuzumab products, serious and fatal infusion reactions have been reported. Severe reactions, which include bronchospasm, anaphylaxis, angioedema, hypoxia, and severe hypotension were usually reported during or immediately following the initial infusion.
Interrupt HERCESSI infusion for dyspnea, clinically significant hypotension, and intervention of medical therapy administered (which may include epinephrine, corticosteroids, diphenhydramine, bronchodilators, and oxygen).
Monitor patients until symptoms completely resolve.
Discontinue HERCESSI for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. Strongly consider permanent discontinuation in all patients with severe infusion reactions.
Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion include nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia.
Embryo-Fetal Toxicity

Exposure to trastuzumab products during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception.
Verify the pregnancy status of females of reproductive potential prior to the initiation of HERCESSI.
Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of HERCESSI. Advise female patients to contact their healthcare provider with a known or suspected pregnancy.
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for HERCESSI treatment and any potential adverse effects on the breastfed child from HERCESSI or from the underlying maternal condition. This consideration should also take into account the trastuzumab product wash out period of 7 months.
Pulmonary Toxicity

Trastuzumab products can result in serious and fatal pulmonary toxicity, which includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions.
Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity.
Discontinue HERCESSI in patients experiencing pulmonary toxicity.
Exacerbation of Chemotherapy-Induced Neutropenia

In randomized, controlled clinical trials, the per-patient incidences of NCI-CTC Grade 3-4 neutropenia and of febrile neutropenia were higher in patients receiving trastuzumab in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received trastuzumab and those who did not.
Most Common Adverse Reactions

The most common adverse reactions associated with trastuzumab products in adjuvant and metastatic breast cancer are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia. Adverse reactions requiring interruption or discontinuation of trastuzumab product treatment include CHF, significant decline in left ventricular cardiac function, severe infusion reactions, and pulmonary toxicity.
In the metastatic gastric cancer setting, the most common adverse reactions (≥10%) that were increased (≥5% difference) in the trastuzumab arm as compared to the chemotherapy alone arm were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia.
The most common adverse reactions which resulted in discontinuation of treatment in the trastuzumab-containing arm in the absence of disease progression were infection, diarrhea, and febrile neutropenia.
Indications
Adjuvant Breast Cancer
HERCESSI (trastuzumab-strf) is indicated in adults for adjuvant treatment of HER2-overexpressing node positive or nodenegative (ER/PR-negative or with one high-risk feature) breast cancer:

as part of a treatment regimen containing doxorubicin, cyclophosphamide and either paclitaxel or docetaxel
as part of a treatment regimen with docetaxel and carboplatin
as a single agent following multi-modality anthracycline-based therapy
Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

Metastatic Breast Cancer
HERCESSI is indicated in adults:

in combination with paclitaxel for the first-line treatment of HER2-overexpressing metastatic breast cancer
as a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease
Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

Metastatic Gastric Cancer
HERCESSI is indicated in adults, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease.

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

HERCESSI (trastuzumab-strf) for injection is available as a single-dose vial for the 150 mg/vial strength and as a multiple-dose vial for the 420 mg/vial strength.

Click here for full Prescribing Information, including Boxed Warnings.