Puma Biotechnology’s NERLYNX® Included in NCCN Clinical Practice Guidelines for the Treatment of Cervical Cancer with a HER2 Mutation

Rhea-AI Summary

Puma Biotechnology (NASDAQ: PBYI) announced that NERLYNX® (neratinib) has been included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Cervical Cancer. The drug is now listed as a second-line or subsequent therapy option for recurrent or metastatic cervical cancer patients with HER2-mutated tumors, receiving a Category 2A designation. The inclusion was based on results from the Phase II SUMMIT trial, which studied patients with histologically confirmed recurrent/metastatic cervical cancer and documented evidence of somatic, activating HER2 mutations.

Positive

• Inclusion in NCCN Guidelines expands NERLYNX's market potential in cervical cancer treatment
• Recognition as second-line therapy option strengthens product positioning
• Category 2A designation validates treatment efficacy

Negative

• to 'useful in certain circumstances' designation
• Restricted to specific patient subset with HER2-mutated tumors

Insights

Oncology Research Analyst

The inclusion of NERLYNX in NCCN guidelines for HER2-mutated cervical cancer represents incremental progress in expanding the drug's market reach. This Category 2A designation provides clinical validation for using neratinib as a second-line or later therapy option, though the "useful in certain circumstances" classification suggests a relatively narrow application.

The addressable market is - HER2 mutations occur in approximately 5% of cervical cancers. With roughly 14,000 new cervical cancer cases annually in the US, this translates to about 700 potential candidates, further reduced when considering only those reaching second-line therapy. At NERLYNX's average annual cost of $150,000, the revenue opportunity likely ranges from $15-30 million annually.

The Phase II SUMMIT trial data supporting this inclusion demonstrates Puma's strategic approach to expanding NERLYNX's utility across HER2-driven cancers. However, the commercial impact will be modest given the small patient population and positioning as a later-line option.

Market Access Specialist

The NCCN guideline inclusion is strategically valuable for reimbursement and market access. NCCN guidelines heavily influence payer coverage policies and this Category 2A designation typically translates to favorable coverage determinations. For context, most commercial payers and Medicare plans generally cover NCCN-recommended therapies with Category 1 or 2A evidence.

While this won't drive substantial revenue growth, it reduces barriers to physician adoption by providing clear clinical pathways and simplifying the prior authorization process. The "useful in certain circumstances" designation accurately reflects neratinib's positioning as a precision medicine option for a specific molecular subset of patients.

LOS ANGELES--(BUSINESS WIRE)-- Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, announced that the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Cervical Cancer were updated to include an addition involving neratinib (NERLYNX®).

The updated NCCN Practice Guidelines for Cervical Cancer include neratinib monotherapy for use as second-line or subsequent therapy for recurrent or metastatic disease as an option for patients with HER2-mutated tumors with a designation of Category 2A. The NCCN Guidelines Category of Preference is designated as “useful in certain circumstances” as a treatment option for patients with HER2-mutated tumors.

This addition was based on results from the Phase II SUMMIT trial (NCT01953926), which enrolled a cohort of patients who were required to have histologically confirmed recurrent/metastatic cervical cancer for which no curative treatment existed, along with documented evidence of a somatic, activating HER2 mutation (Friedman CF, D'Souza A, Bello Roufai D, et al. Targeting HER2-mutant metastatic cervical cancer with neratinib: Final results from the Phase II SUMMIT basket trial. Gynecol Oncol. 2024;181:162-169. doi: 10.1016/j.ygyno.2023.12.004).

Alan H. Auerbach, Chief Executive Officer and President of Puma, said, “We are pleased with the additional inclusion of neratinib in the NCCN Guidelines for Cervical Cancer for patients with HER2 activating mutations. Physicians use the NCCN Guidelines as the standard resource for determining the best course of treatment for patients. We believe the updated NCCN guidelines will increase awareness, which will help assist patients, their caregivers and their healthcare providers in making informed decisions while treating this significant unmet need in advanced cervical cancer.”

About HER2-Mutated Cervical Cancer

Despite recent advancements in the therapeutic landscape for recurrent and metastatic cervical cancer, there is a need to identify robust biomarkers to direct therapy choices to target mutational drivers. Somatic HER2 (ERBB2) mutations have been reported in up to 9% ^1,2,3 of cervical cancers and are associated with poor prognosis ^1,2. In a recent real-world study, prospective genomic profiling of cervical cancer patients identified HER2 mutations as one of the more prevalent genomic alterations in the studied cervical cancer population³.

About the National Comprehensive Cancer Network

The National Comprehensive Cancer Network® (NCCN®) is a not-for-profit alliance of leading cancer centers devoted to patient care, research, and education. NCCN is dedicated to improving and facilitating quality, effective, efficient, and accessible cancer care so patients can live better lives. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) provide transparent, evidence-based, expert consensus recommendations for cancer treatment, prevention, and supportive services; they are the recognized standard for clinical direction and policy in cancer management and the most thorough and frequently updated clinical practice guidelines available in any area of medicine. The NCCN Guidelines for Patients® provide expert cancer treatment information to inform and empower patients and caregivers, through support from the NCCN Foundation®. NCCN also advances continuing education, global initiatives, policy, and research collaboration and publication in oncology. Visit NCCN.org for more information.

About Puma Biotechnology

Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialization of innovative products to enhance cancer care. Puma in-licensed the global development and commercialization rights to PB272 (neratinib, oral), in 2011. Neratinib, oral was approved by the U.S. Food and Drug Administration in 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX® (neratinib) tablets. In February 2020, NERLYNX was also approved by the FDA in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. NERLYNX was granted marketing authorization by the European Commission in 2018 for the extended adjuvant treatment of adult patients with early stage hormone receptor-positive HER2-overexpressed/amplified breast cancer and who are less than one year from completion of prior adjuvant trastuzumab-based therapy. NERLYNX® is a registered trademark of Puma Biotechnology, Inc.

In September 2022, Puma entered into an exclusive license agreement for the development and commercialization of the anti-cancer drug alisertib, a selective, small molecule, orally administered inhibitor of aurora kinase A. Initially, Puma intends to focus the development of alisertib on the treatment of small cell lung cancer and breast cancer. In February 2024, Puma initiated ALISCA™-Lung1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive-stage small cell lung cancer. In November 2024, Puma initiated ALISCA™-Breast1, a Phase II clinical trial of alisertib in combination with endocrine therapy for the treatment of patients with HER2-negative, HR-positive metastatic breast cancer.

To help ensure patients have access to NERLYNX, Puma has implemented the Puma Patient Lynx support program to assist patients and healthcare providers with reimbursement support and referrals to resources that can help with financial assistance. More information on the Puma Patient Lynx program can be found at https://www.NERLYNX.com or by dialing 1-855-816-5421.

Further information about Puma Biotechnology may be found at https://www.pumabiotechnology.com.

INDICATIONS

• NERLYNX® (neratinib) tablets, for oral use, is a kinase inhibitor indicated:
• As a single agent, for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer, to follow adjuvant trastuzumab-based therapy.
• In combination with capecitabine, for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer, who have received two or more prior anti-HER2 based regimens in the metastatic setting.

Important Safety Information Regarding NERLYNX® (neratinib) U.S. Indication

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

• Diarrhea: Manage diarrhea through either NERLYNX dose escalation or loperamide prophylaxis. If diarrhea occurs despite recommended prophylaxis, treat with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe and/or persistent diarrhea. Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade ≥ 2 diarrhea that occurs after maximal dose reduction.
• Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. Withhold NERLYNX in patients experiencing Grade 3 liver abnormalities and permanently discontinue NERLYNX in patients experiencing Grade 4 liver abnormalities.
• Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.

ADVERSE REACTIONS: The most common adverse reactions (reported in ≥ 5% of patients) were as follows:

• NERLYNX as a single agent: Diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increased, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased, and urinary tract infection.
• NERLYNX in combination with capecitabine: Diarrhea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, weight decreased, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract infection, abdominal distention, renal impairment, and muscle spasms.

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS:

• Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors. Separate NERLYNX by at least 2 hours before or 10 hours after H2-receptor antagonists. Or separate NERLYNX by at least 3 hours with antacids.
• Strong CYP3A4 inhibitors: Avoid concomitant use.
• P-gp and moderate CYP3A4 dual inhibitors: Avoid concomitant use.
• Strong or moderate CYP3A4 inducers: Avoid concomitant use.
• Certain P-gp substrates: Monitor for adverse reactions of P-gp substrates for which minimal concentration change may lead to serious adverse reactions when used concomitantly with NERLYNX.

USE IN SPECIFIC POPULATIONS:

• Lactation: Advise women not to breastfeed.

Please see Full Prescribing Information for additional safety information.

¹ Xiang L, Jiang W, Ye S, He T, Pei X, Li J, et al. ERBB2 mutation: A promising target in non-squamous cervical cancer. Gynecol Oncol. 2018;148(2):311-316.

² Zammataro L, Lopez S, Bellone S, Pettinella F, Bonazzoli E, Perrone E, et al. Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy. Proc Natl Acad Sci U S A. 2019;116(45):22730-22736.

³ Friedman CF, Ravichandran V, Miller K, et al. Assessing the genomic landscape of cervical cancers: clinical opportunities and therapeutic targets. Clin Cancer Res. 2023;29(22):4660-4668. doi: 10.1158/1078-0432.CCR-23-1078. PMID: 37643132; PMCID: PMC10644000.

View source version on businesswire.com: https://www.businesswire.com/news/home/20241223490944/en/

Alan H. Auerbach or Mariann Ohanesian, Puma Biotechnology, Inc., +1 424 248 6500

info@pumabiotechnology.com

ir@pumabiotechnology.com

David Schull or Olipriya Das, Russo Partners, +1 212 845 4200

david.schull@russopartnersllc.com

olipriya.das@russopartnersllc.com

Source: Puma Biotechnology, Inc.

FAQ

What is the new NCCN guideline update for PBYI's NERLYNX in cervical cancer treatment?

NERLYNX has been included as a second-line or subsequent therapy option for recurrent or metastatic cervical cancer patients with HER2-mutated tumors, receiving a Category 2A designation.

Which clinical trial supported NERLYNX's inclusion in NCCN guidelines for cervical cancer?

The Phase II SUMMIT trial (NCT01953926) supported the inclusion, studying patients with recurrent/metastatic cervical cancer and documented HER2 mutations.

What is the Category of Preference designation for NERLYNX in the NCCN Guidelines?

NERLYNX is designated as 'useful in certain circumstances' as a treatment option for patients with HER2-mutated tumors.

What patient population can benefit from NERLYNX according to the new NCCN guidelines?

Patients with recurrent or metastatic cervical cancer who have HER2-mutated tumors can benefit from NERLYNX as a second-line or subsequent therapy.