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Hyrnuo Sevabertinib 10 mg Tablet, Film Coated, 120-count — NDC 50419-0397-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Hyrnuo Sevabertinib 10 mg Tablet, Film Coated, 120-count — NDC 50419-397-01 (Billing 50419-0397-01)

by Bayer HealthCare Pharmaceuticals Inc. · 120 TABLET, FILM COATED in 1 BOTTLE

This is a package of 120 tablets of Hyrnuo Sevabertinib 10 mg Tablet, Film Coated from Bayer HealthCare Pharmaceuticals Inc., marketed since Nov 2025 and currently FDA-listed. It is this product's only package size.

NDC 50419-0397-01
🏷️ FDA NDC (as labeled) 50419-397-01 billing pads the product segment with a zero
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Oct 1, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 50419-397-01
Product NDC 50419-397
11-digit billing NDC 50419039701
NCPDP billing unit EA — each (per item)
Application # NDA219972
SPL Set ID d7a11334-6e7a-445b-9a16-bdcd9acbe61f
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2025-11-19
Route ORAL
Dosage form TABLET, FILM COATED
Substance SEVABERTINIB

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GCN Seq No 088432
GCN 58561
HICL code 051015
Ingredient (HICL) Sevabertinib
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1Q
Therapeutic class — specific (HIC3) Antineoplastic Systemic Enzyme Inhibitors
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name HYRNUO 10 MG TABLET
FDB brand name Hyrnuo
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 088432
  • GCN: 58561
  • HICL (First Databank): 051015
  • AHFS class code: 10:00.00.00
Why two NDCs? The FDA registers this code as 50419-397-01 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 50419-0397-01. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

Clinical

Label name HYRNUO 10 MG TABLET Ingredient Sevabertinib
📖 What it is MedlinePlus · NLM

Sevabertinib is used to treat certain types of non-small cell lung cancer (NSCLC; a type of lung cancer). Sevabertinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells.

Read the full MedlinePlus article ↗

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $202.81 $24,336.79 / 120 tablets
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
50419-0397-01 You're viewing this Main listing 120 TABLET, FILM COATED in 1 BOTTLE 2025-11-19 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Hyrnuo 10 mgthis 50419-0397-01 Bayer 120 tablets — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2025
First FDA approval
Nov 2025
📍
2026
Currently FDA-listed
1 year listed
🛡️
2043
Latest patent/protection listed
not a guaranteed launch date
🔒No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Nov 2043. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Nov 19, 2025 RLD RS ⏳ ~17.1 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 12679836 — drug substance (U-4582)
US 10428063 — drug substance
Exclusivity NCE
2025 2027 2029 2031 2033 2035 2037 2039 2041 2043
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (2)
PatentTypeUse codeExpires
US 12679836 ↗ Drug substance U-4582 Nov 14, 2043
US 10428063 ↗ Drug substance — Oct 10, 2035
FDA exclusivity
CodeWhat it grantsExpires
NCENew Chemical Entity (5-year)Nov 19, 2030
Common questions
Is there a generic version of HYRNUO 10 MG TABLET?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for HYRNUO 10 MG TABLET. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Nov 2043 — an estimate, not a guaranteed launch date.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

What it looks like

Color Red
ShapeRound
ImprintSE;10
Size6 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII 2S7830E561
    Crospovidone is a synthetic polymer derived from povidone. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the active ingredient can be absorbed.
  • UNII 1K09F3G675
    Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
  • UNII 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
  • UNII EWQ57Q8I5X
    Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII G2M7P15E5P
    Polyethylene glycol 3350 is a synthetic polymer used as a solvent, humectant, and thickening agent in medicines. It helps dissolve other ingredients, retain moisture in the product, and achieve the desired consistency.

7 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerBayer HealthCare Pharmaceuticals Inc.
Application holderBAYER HEALTHCARE PHARMACEUTICALS INC
FDA applicationNDA219972 (NDA)
Labeler code50419
First marketedNov 2025
Product typeHuman Prescription Drug
Portfolio62 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 191 words ▾

1 INDICATIONS AND USAGE HYRNUO is indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 ( ERBB2 ) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test [see Dosage and Administration (2.1) ] , and who have received a prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR) [see Clinical Studies (14) ] .

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. HYRNUO is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 ( ERBB2 ) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. ( 1 ) This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR).

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Select patients for treatment with HYRNUO based on the presence of HER2 ( ERBB2 ) TKD activating mutations. ( 2.1 ) Recommended Dosage : 20 mg orally twice daily with food until disease progression or unacceptable toxicity. Swallow tablets whole. ( 2.2 )

2.1Patient Selection Select patients for treatment of locally advanced or metastatic non-squamous NSCLC based on the presence of HER2 ( ERBB2 ) TKD activating mutations in tumor specimens [see Clinical Studies (14) ] . Information on FDA-approved tests is available at http://www.fda.gov/CompanionDiagnostics.

2.2Recommended Dosage The recommended dosage of HYRNUO is 20 mg orally twice daily with food, until disease progression or unacceptable toxicity [see Clinical Pharmacology (12.3) ] . Swallow tablets whole. Do not cut, crush, or chew tablets.

Missed Dose If a dose is missed, take the missed dose as soon as you remember prior to the next scheduled dose. Do not take 2 doses at the same time to make up for the missed dose. Vomited Dose If a dose is vomited, do not take an additional dose.

Resume dosing at the next scheduled time.

2.3Dosage Modifications for Adverse Reactions The recommended dosage reductions for adverse reactions are provided in Table 1. Table 1: Recommended HYRNUO Dosage Reductions for Adverse Reactions Dose Reduction Dosage Modification First 10 mg twice daily Second 10 mg once daily Permanently discontinue HYRNUO in patients who are unable to tolerate 10 mg once daily. The recommended dosage modifications for adverse reactions are provided in Table 2.

Table 2: Recommended HYRNUO Dosage Modifications for Adverse Reactions Adverse Reaction Severity Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Dosage Modification Diarrhea [see Warnings and Precautions (5.1) ] Intolerable Grade 2 or Grade 3 Interrupt HYRNUO until recovery to Grade ≤1. Resume HYRNUO at the same dose or the next lower dose.

For recurrence, resume HYRNUO at the next lower dose. Grade 4 Permanently discontinue HYRNUO. Hepatotoxicity [see Warnings and Precautions (5.2) ] Grade 2, 3 or 4 ALT and/or AST without increased total bilirubin or Grade 3 total bilirubin Interrupt HYRNUO until recovery to Grade ≤1 or baseline.

Resume HYRNUO at the next lower dose. ALT or AST ≥ 3× ULN with total bilirubin ≥ 2× ULN or Grade 4 total bilirubin Permanently discontinue HYRNUO. Interstitial lung disease (ILD)/pneumonitis [see Warnings and Precautions (5.3) ] Any Grade Permanently discontinue HYRNUO.

Ocular toxicity [see Warnings and Precautions (5.4) ] Grade 2 Interrupt HYRNUO until recovery to Grade ≤1. Resume HYRNUO at the next lower dose. For recurrence, permanently discontinue HYRNUO.

Grade 3 or Grade 4 Permanently discontinue HYRNUO. Pancreatic Enzyme Elevation [see Warnings and Precautions (5.5) ] Grade 3 Interrupt HYRNUO until recovery to Grade ≤2 or baseline. Resume HYRNUO at the next lower dose.

Grade 4 Permanently discontinue HYRNUO. Other adverse reactions [see Adverse Reactions (6.1) ] Intolerable or recurrent Grade 2 or Grade 3 Interrupt HYRNUO until recovery to Grade ≤1. Resume HYRNUO at the same dose or the next lower dose.

For recurrence, resume HYRNUO at the next lower dose. Grade 4 Permanently discontinue HYRNUO.

2.4Dosage Modifications for Strong CYP3A Inhibitors Avoid concomitant use of strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce HYRNUO dosage as shown in Table 3. After the CYP3A inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the HYRNUO dosage that was used prior to initiating the inhibitor [see Drug Interactions (7.1) ].

Table 3: Recommended HYRNUO Dosage Modifications for Concomitant Use with Strong CYP3A Inhibitors Current Dosage Recommended Dosage 20 mg twice daily 10 mg twice daily 10 mg twice daily 10 mg once daily 10 mg once daily Withhold HYRNUO until strong CYP3A inhibitor is discontinued

💊 Dosage Forms and Strengths 37 words ▾

3 DOSAGE FORMS AND STRENGTHS Tablets: red brown film-coated, round, biconvex tablets debossed with "SE" on one side and "10" on the other side containing 10 mg of sevabertinib. Tablets: 10 mg of sevabertinib. ( 3 )

⛔ Contraindications 7 words ▾

4 CONTRAINDICATIONS None. None. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Diarrhea : At the first sign of diarrhea or increased bowel movement frequency, instruct patients to start an antidiarrheal treatment, and to increase their fluid and electrolyte intake. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity. ( 5.1 ) Hepatotoxicity : Monitor liver function tests including ALT, AST, and total bilirubin at baseline prior to administration of HYRNUO, every 2 weeks during the first month, and then monthly thereafter as clinically indicated, with more frequent testing in patients who develop transaminase elevations.

Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity. ( 5.2 ) Interstitial Lung Disease (ILD)/Pneumonitis : Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Discontinue HYRNUO upon confirmation of ILD/pneumonitis.

( 5.3 ) Ocular Toxicity : Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Interrupt, reduce the dose or permanently discontinue HYRNUO based on severity. ( 5.4 ) Pancreatic Enzyme Elevation : Monitor amylase and lipase regularly during treatment.

Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity. ( 5.5 ) Embryo-fetal toxicity : Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

( 5.6 , 8.1 , 8.3 )

5.1Diarrhea HYRNUO can cause severe diarrhea that can lead to dehydration and electrolyte imbalances. In the pooled safety population [see Adverse Reactions (6.1) ] , diarrhea was reported in 86% of patients who received HYRNUO including Grade 3 in 15%. The median time to first onset of any grade diarrhea was four days.

Dosage interruptions occurred in 15% of patients, and dose reductions occurred in 12% of patients. At the first sign of diarrhea or increased bowel movement frequency, instruct patients to start an antidiarrheal treatment (e.g., loperamide [refer to full Prescribing Information] ), and to increase their fluid and electrolyte intake. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity [see Dosage and Administration (2.3) ] .

5.2Hepatotoxicity HYRNUO can cause severe hepatotoxicity characterized by elevations of liver function tests. In the pooled safety population [see Adverse Reactions (6.1) ], based on adverse reaction data, hepatotoxicity occurred in 24% of patients treated with HYRNUO including 3% Grade 3. Based on laboratory data, 35% of patients treated with HYRNUO experienced increased alanine aminotransferase (ALT), including 2.3% Grade 3.

Increased aspartate aminotransferase (AST) occurred in 35% of patients treated with HYRNUO, including 2.3% Grade 3. Increased bilirubin occurred in 12% of patients treated with HYRNUO. The median time to first onset of AST or ALT elevation was 1.4 (range 0.2 to 14.5) months.

HYRNUO was interrupted for an adverse reaction of hepatotoxicity in 4.1% of patients, the dose was reduced in 4.1% and permanently discontinued in 0.4%. Monitor liver function tests including ALT, AST, and total bilirubin at baseline prior to the first administration of HYRNUO, every 2 weeks for the first month, and then monthly thereafter as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on the severity of the adverse reaction [see Dosage and Administration (2.3) ] .

5.3Interstitial Lung Disease/Pneumonitis HYRNUO can cause severe interstitial lung disease (ILD)/pneumonitis. In the pooled safety population [see Adverse Reactions (6.1) ], ILD/pneumonitis occurred in two patients (0.7%) treated with HYRNUO, including 0.4% Grade 3. One patient required interruption of HYRNUO.

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Discontinue HYRNUO upon confirmation of ILD/pneumonitis [see Dosa… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Diarrhea [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.3) ] Ocular Toxicity [see Warnings and Precautions (5.4) ] Pancreatic Enzyme Elevation [see Warnings and Precautions (5.5) ] Most common adverse reactions (>20%) : diarrhea, rash, paronychia, stomatitis, and nausea.

Most common Grade 3 or 4 laboratory abnormalities (≥2%) : decreased potassium, increased lipase, decreased lymphocyte count, decreased sodium, increased amylase, increased ALT, and increased AST. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-842-2937 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population in the WARNINGS AND PRECAUTIONS reflects exposure to HYRNUO at 20 mg orally twice daily in 268 patients with locally advanced or metastatic NSCLC harboring HER2 and/or other mutations from the SOHO-01 study [see Clinical Studies (14) ] .

Among 268 patients who received HYRNUO, 35% were exposed for greater than 6 months and 12% were exposed for greater than 1 year. In this pooled safety population, the most common (>20%) adverse reactions were diarrhea, rash, stomatitis, and paronychia. The most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased potassium, increased lipase, decreased lymphocyte count, decreased sodium, increased amylase, increased ALT, and increased AST.

The safety of HYRNUO at 20 mg orally twice daily was evaluated in 136 patients with locally advanced or metastatic NSCLC harboring HER2 activating mutations who had received prior systemic therapy in the SOHO-01 study [see Clinical Studies (14) ] . Among 136 patients who received HYRNUO, 46% were exposed greater than 6 months and 15% were exposed for greater than 1 year. The median age of patients who received HYRNUO was 62 years (range: 29 to 91); 63% female; 65% Asian, 27% White, 3.7% Black or African American; and 2.2% were of Hispanic or Latino ethnicity.

The most common adverse reactions (>20%) in patients who received HYRNUO were diarrhea, rash, paronychia, stomatitis, and nausea. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were potassium decreased, lipase increased, lymphocyte count decreased, sodium decreased, amylase increased, aspartate aminotransferase (AST) increased, and alanine aminotransferase (ALT) increased. Serious adverse reactions occurred in 31% of patients who received HYRNUO.

Serious adverse reactions in ≥2% of patients were diarrhea (6%), pneumonia (3.7%), dyspnea (2.2%), and pleural effusion (2.2%). Permanent discontinuation of HYRNUO due to an adverse reaction occurred in 3.7% of patients. Adverse reactions which resulted in permanent discontinuation were corneal epithelial microcysts, hepatic function abnormal, electrocardiogram QT prolonged, pain in extremity and dyspnea (0.7%, 1 patient each).

Dosage interruptions of HYRNUO due to an adverse reaction occurred in 46% of patients. Adverse reactions which resulted in dosage interruptions in >3% of patients were diarrhea, hypokalemia, nausea, decreased appetite, and pneumonia. Dose reductions of HYRNUO due to adverse reactions occurred in 28% of patients.

Adverse reactions which resulted in dose reductions in >2% of patients were diarrhea, rash, and hypokalemia. Table 4 summarizes the adverse reactions in SOHO-01 (Groups D and E). Table 4: Adverse Reactions (≥10%) in Patients with NSCLC with HER2 Activating Mutations Who Received HYRNUO in SOHO-01 (Groups D and E)… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Strong CYP3A Inhibitors: Avoid concomitant use with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce HYRNUO dosage. ( 2.4 , 7.1 ).

Moderate CYP3A Inhibitors: Monitor patients for increased HYRNUO-associated adverse reactions ( 2.3 , 7.1 ) Strong and Moderate CYP3A Inducers: Avoid concomitant use with strong or moderate CYP3A inducers. ( 7.1 ) Certain CYP3A Substrates: Avoid concomitant use with CYP3A substrates where minimal increases in concentration may lead to serious adverse reactions unless otherwise recommended in the Prescribing Information of the CYP3A substrate. ( 7.2 ) Certain P-gp Substrates: Refer to the Prescribing Information for P-gp substrates where minimal increases in concentration may lead to serious adverse reactions ( 7.2 )

7.1Effect of Other Drugs on HYRNUO Table 6 describes drug interactions where concomitant use of another drug affects HYRNUO. Table 6: Drug Interactions that Affect HYRNUO Strong and Moderate CYP3A Inhibitors Prevention or management Strong CYP3A Inhibitors : Avoid concomitant use of HYRNUO with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce HYRNUO dosage [see Dosage and Administration (2.4) ] .

Moderate CYP3A Inhibitors : Monitor patients for increased HYRNUO-associated adverse reactions [see Dosage and Administration (2.3) ] . Mechanism and Clinical Effect Sevabertinib is a CYP3A substrate. Concomitant use with a strong or moderate CYP3A inhibitor may increase sevabertinib plasma concentrations [see Clinical Pharmacology (12.3) ] , which may increase the risk of HYRNUO-associated adverse reactions.

Strong and Moderate CYP3A Inducers Prevention or management Avoid concomitant use of HYRNUO with strong or moderate CYP3A inducers. Mechanism and Clinical Effect Sevabertinib is a CYP3A substrate. Concomitant use with a strong or moderate CYP3A inducer may decrease sevabertinib plasma concentrations [see Clinical Pharmacology (12.3) ], which may decrease the effectiveness of HYRNUO.

7.2Effects of HYRNUO on Other Drugs Table 7 describes drug interactions where concomitant use of HYRNUO affects another drug. Table 7: HYRNUO Drug Interactions that Affect Other Drugs Certain CYP3A Substrates Prevention or management Avoid concomitant use of HYRNUO with CYP3A substrates where minimal increases in the concentration may lead to serious adverse reactions unless otherwise recommended in the Prescribing Information of the CYP3A substrate. Mechanism and Clinical Effect Sevabertinib is a weak to moderate CYP3A inhibitor.

Sevabertinib increases exposure of CYP3A substrates [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions related to these substrates. Certain P-gp Substrates Prevention or management Refer to the Prescribing Information for P-gp substrates where minimal increases in the concentration may lead to serious adverse reactions. Mechanism and Clinical Effect Sevabertinib is a P-gp inhibitor.

Sevabertinib increases exposure of P-gp substrates [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions related to these substrates. CYP1A1 Substrates Prevention or management Refer to the Prescribing Information of CYP1A1 substrates. Mechanism and Clinical Impact Sevabertinib is an inhibitor of CYP1A1 in vitro.

Sevabertinib may increase exposure of CYP1A1 substrates [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions related to these substrates.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation : Advise not to breastfeed. ( 8.2 )

8.1Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , HYRNUO can cause fetal harm when administered to a pregnant woman. There are no available data on the use of HYRNUO in pregnant women to inform a drug-associated risk. In embryo-fetal development studies, oral administration of sevabertinib to pregnant rats during the period of organogenesis resulted in alterations to growth at maternal exposures ≥0.18 times the human exposure based on area under the curve (AUC) at the clinical dose of 20 mg twice daily.

Animal studies with disrupted or depleted HER2/EGFR and in vitro assays have demonstrated that inhibition of HER2 and/or EGFR results in structural abnormalities, alteration to growth, and embryo-fetal and infant mortality (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal Data In embryo-fetal development studies, sevabertinib was administered orally to pregnant rats during the period of organogenesis from gestation day 6 to 17 at doses ranging from 1.5 to 11 mg/kg/day. Sevabertinib treatment resulted in maternal toxicity (reduced body weight and body weight gain) and a reduction in fetal weights at ≥6 mg/kg/day (≥0.18 times the human exposure based on AUC at the clinical dose). Additional Nonclinical Data A literature-based assessment of the effects on reproduction in mouse models with disrupted or depleted HER2 / EGFR demonstrated that HER2/EGFR is critically important in reproductive and developmental processes including blastocyst implantation, placental development, and embryo-fetal/postnatal survival and development.

In a human-induced pluripotent stem cell-based assay, sevabertinib reduced cardiomyocyte and hepatocyte differentiation markers.

8.2Lactation Risk Summary There are no data on the presence of sevabertinib or its metabolites in human milk or their effects on a breastfed child or on milk production. In rats, sevabertinib or its metabolites are excreted in milk (see Data ) . Because of the potential for serious adverse reactions in breastfed children from HYRNUO, advise women not to breastfeed during treatment with HYRNUO and for 1 week after the last dose.

Data Animal Data Following administration of radiolabeled sevabertinib to lactating rats, sevabertinib or its metabolites were excreted in milk. Sevabertinib-derived radioactivity concentrations were 13- to 26-times higher in milk than in plasma. Approximately 1.3% of the administered dose of sevabertinib-derived radioactivity was excreted into the milk.

8.3Females and Males of Reproductive Potential HYRNUO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating HYRNUO. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with HYRNUO and for 1 week after the last dose.

Males Advise males with female partners of reproductive potential to use effective contraception during treatment with HYRNUO and for 1 week after the last dose.

8.4Pediatric Use The safety and effectiveness of HYRNUO have not been established in pediatric patients.

8.5Geriatric Use Of the 268 patients with locally advanced or metastatic NSCLC harboring HER2 activating mutations who received HYRNUO at 20 mg twice daily in the SOHO-01study, 43% were 65 years and over and 13% were 75 years and over. No overall differences in effectiveness were observed between these older and younger patients. Grade 3 diarrhea was observed in 23% of patients age ≥75 years and 14% of patients <75 years old.

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , HYRNUO can cause fetal harm when administered to a pregnant woman. There are no available data on the use of HYRNUO in pregnant women to inform a drug-associated risk. In embryo-fetal development studies, oral administration of sevabertinib to pregnant rats during the period of organogenesis resulted in alterations to growth at maternal exposures ≥0.18 times the human exposure based on area under the curve (AUC) at the clinical dose of 20 mg twice daily.

Animal studies with disrupted or depleted HER2/EGFR and in vitro assays have demonstrated that inhibition of HER2 and/or EGFR results in structural abnormalities, alteration to growth, and embryo-fetal and infant mortality (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal Data In embryo-fetal development studies, sevabertinib was administered orally to pregnant rats during the period of organogenesis from gestation day 6 to 17 at doses ranging from 1.5 to 11 mg/kg/day. Sevabertinib treatment resulted in maternal toxicity (reduced body weight and body weight gain) and a reduction in fetal weights at ≥6 mg/kg/day (≥0.18 times the human exposure based on AUC at the clinical dose). Additional Nonclinical Data A literature-based assessment of the effects on reproduction in mouse models with disrupted or depleted HER2 / EGFR demonstrated that HER2/EGFR is critically important in reproductive and developmental processes including blastocyst implantation, placental development, and embryo-fetal/postnatal survival and development.

In a human-induced pluripotent stem cell-based assay, sevabertinib reduced cardiomyocyte and hepatocyte differentiation markers.

🧒 Pediatric Use 16 words ▾

8.4Pediatric Use The safety and effectiveness of HYRNUO have not been established in pediatric patients.

🧓 Geriatric Use 73 words ▾

8.5Geriatric Use Of the 268 patients with locally advanced or metastatic NSCLC harboring HER2 activating mutations who received HYRNUO at 20 mg twice daily in the SOHO-01study, 43% were 65 years and over and 13% were 75 years and over. No overall differences in effectiveness were observed between these older and younger patients. Grade 3 diarrhea was observed in 23% of patients age ≥75 years and 14% of patients <75 years old.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Sevabertinib is a reversible kinase inhibitor of human epidermal growth factor receptor 2 (HER2). It also exhibits activity against epidermal growth factor receptor (EGFR). In vitro, sevabertinib inhibited the phosphorylation of HER2 and downstream signaling in cancer cells with HER2 alterations and proliferation of cancer cells overexpressing wild-type HER2 or harboring HER2 mutations.

In vivo, sevabertinib demonstrated antitumor activity in subcutaneous mouse xenograft models derived from human NSCLC tumors harboring an activating HER2 exon 20 mutation.

12.2Pharmacodynamics Exposure-Response Relationship Higher sevabertinib exposure, across the dose range of 10 to 80 mg total daily dose (0.25 to 2 times the recommended dosage), was associated with an increased incidence of diarrhea (all grade and Grade ≥3) and rash. Cardiac Electrophysiology At 2 times the maximum recommended dose, a mean increase in the QTc interval >20 ms was not observed.

12.3Pharmacokinetics Sevabertinib pharmacokinetics were observed at steady state in patients with advanced NSCLC harboring activating HER2 or EGFR mutations at the approved recommended dosage and are presented as mean (CV%), unless otherwise specified. Sevabertinib maximum concentration (C max ) is 902 (45%) ng/mL and total systemic exposure (AUC) is 6,640 (50%) ng*h/mL. Sevabertinib C max and AUC increase in a dose-proportional manner across the dose range of 10 mg to 80 mg (0.25 to 2 times the approved recommended total daily dose).

Sevabertinib accumulation is approximately 1.7-fold for AUC and 1.3-fold for C max at the approved recommended dosage. Steady state is achieved within 3 days. Absorption Sevabertinib median (min, max) time to maximum concentrations (T max ) is approximately 2 hours (0.5, 8.2 hours) after a single dose.

Effect of Food Sevabertinib C max decreases by 56% and AUC decreases by 28% with a high-fat meal (1000 calories, 50% fat) in healthy subjects. No clinically significant differences in sevabertinib pharmacokinetics were observed following administration of a low-fat meal (400 calories, 25% fat). Distribution Sevabertinib apparent volume of distribution is 28 L (42%).

Sevabertinib plasma protein binding is 95%. The blood-to-plasma concentration ratio is 0.6. Elimination Sevabertinib effective half-life is approximately 8 hours (33%) with an apparent clearance of

3.1L/hour (38%). Metabolism Sevabertinib is primarily metabolized by CYP3A (major), CYP1A1 (minor), and glucuronidation (minor). Excretion After a single oral dose of radiolabeled sevabertinib 40 mg to healthy subjects, approximately 84% of the dose was recovered in feces (14% unchanged) and approximately 10% in urine (1.3% unchanged).

Specific Populations No clinically significant effects in the pharmacokinetics of sevabertinib were observed based on age (18 to 91 years), race (27% White, 65% Asian, 2.7% Black/African American), sex, body weight (29 to 155 kg), smoking status, eGFR 30 to < 90 mL/min, or mild hepatic impairment (AST > ULN and total bilirubin ≤ ULN; or total bilirubin >1 to 1.5× ULN and any AST). The effect of severe renal impairment (eGFR 15 to <30 mL/min), end-stage renal disease (eGFR <15 mL/min), moderate hepatic impairment (total bilirubin >1.5 to 3× ULN and any AST) or severe hepatic impairment (total bilirubin > 3× ULN and any AST) on sevabertinib pharmacokinetics is unknown.

Drug Interaction Studies Clinical Studies Strong CYP3A Inhibitors: Sevabertinib AUC increased 2.3-fold and C max 1.6-fold following concomitant use of itraconazole (strong CYP3A inhibitor) 200 mg once daily. Strong CYP3A Inducers: Sevabertinib AUC decreased by 79% and C max by 57% following concomitant use of carbamazepine (strong CYP3A inducer) 600 mg once daily. CYP3A Substrates: Midazolam (CYP3A substrate) AUC increased 2-fold and C max 1.8-fold following concomitant use of HYRNUO 20 mg twice daily.

P-gp Substrates: Dabigatran etexilate (P-gp substrate)… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 80 words ▾

12.1Mechanism of Action Sevabertinib is a reversible kinase inhibitor of human epidermal growth factor receptor 2 (HER2). It also exhibits activity against epidermal growth factor receptor (EGFR). In vitro, sevabertinib inhibited the phosphorylation of HER2 and downstream signaling in cancer cells with HER2 alterations and proliferation of cancer cells overexpressing wild-type HER2 or harboring HER2 mutations.

In vivo, sevabertinib demonstrated antitumor activity in subcutaneous mouse xenograft models derived from human NSCLC tumors harboring an activating HER2 exon 20 mutation.

📦 How Supplied / Storage and Handling 78 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied HYRNUO 10 mg tablets are supplied as red brown film-coated, round, biconvex tablets debossed with "SE" on one side and "10" on the other side. HYRNUO tablets are packaged in a HDPE bottle of 120 tablets closed with a child-resistant screw cap. NDC 50419-397-01 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [ see USP Controlled Room Temperature ].

📦 Storage and Handling 27 words ▾

Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [ see USP Controlled Room Temperature ].

📋 Description 133 words ▾

11 DESCRIPTION HYRNUO tablets contain sevabertinib, a kinase inhibitor. The chemical name of the drug substance is 3-(3-chloro-2-methoxyanilino)-2-{3-[(2S)-1,4-dioxan-2-ylmethoxy]pyridin-4-yl}-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one hydrate. The molecular formula is C 24 H 25 ClN 4 O 5 (anhydrate) and the molecular weight is 484.93 g/mol (anhydrate).

The structural formula is shown below: Sevabertinib is present as a non-stoichiometric hydrate as a white to off-white to yellow to pinkish powder. It is slightly soluble in aqueous solution at pH 2, and practically insoluble in aqueous solutions at pH 4.5 and above. The strength of HYRNUO is based on the anhydrate form.

Each HYRNUO tablet for oral use contains 10 mg of sevabertinib. The inactive ingredients are: cellulose microcrystalline, crospovidone, lactose monohydrate, and magnesium stearate. The tablet film coating contains ferric oxide red, hypromellose 5 cP, and macrogol 3350.

Chemical Structure

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Diarrhea Inform patients that HYRNUO can cause severe diarrhea. At the first sign of diarrhea or increased bowel movement frequency, instruct patients to start an antidiarrheal treatment (e.g., loperamide), to increase their fluid and electrolyte intake, and to immediately contact their healthcare provider [see Warnings and Precautions (5.1) ] .

Hepatotoxicity Inform patients that HYRNUO can cause severe hepatotoxicity characterized by elevations of liver function tests. Inform patients that they will need to undergo lab tests to monitor hepatic function. Advise patients to immediately contact their healthcare provider for signs and symptoms of hepatotoxicity [see Warnings and Precautions (5.2) ].

Interstitial Lung Disease (ILD)/Pneumonitis Inform patients that HYRNUO can cause severe ILD/pneumonitis. Advise patients to immediately contact their healthcare provider for new or worsening respiratory symptoms [see Warnings and Precautions (5.3) ]. Ocular Toxicity Inform patients that HYRNUO can cause ocular toxicity.

Advise patients to immediately contact their healthcare provider for new or worsening ocular symptoms [see Warnings and Precautions (5.4) ]. Pancreatic Enzyme Elevation Inform patients that HYRNUO can cause pancreatic enzyme elevation. Inform patients that they will need to undergo lab tests to monitor pancreatic function.

Advise patients to immediately contact their healthcare provider for signs and symptoms associated with pancreatic enzyme elevation [see Warnings and Precautions (5.5) ]. Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.6) and Use in Specific Populations (8.1 , 8.3) ] .

Advise females of reproductive potential to use effective contraception during treatment with HYRNUO and for 1 week after the last dose [see Use in Specific Populations (8.3) ] . Advise male patients with female partners of reproductive potential to use effective contraception during treatment with HYRNUO and for 1 week after the last dose [see Use in Specific Populations (8.3) ] . Lactation Advise women not to breastfeed during treatment with HYRNUO and for 1 week after the last dose [see Use in Specific Populations (8.2) ] .

Dosage and Administration Instruct patients to take HYRNUO twice daily with food. Each tablet should be swallowed whole [see Dosage and Administration (2.2) ]. Instruct patients that if a dose of HYRNUO is missed to take the missed dose as soon as they remember prior to the next scheduled dose.

Advise patients not to take two doses together to make up for a missed dose [see Dosage and Administration (2.2) ]. Instruct patients that if a dose of HYRNUO is vomited not to take an additional dose but to take the next dose at the next scheduled time [see Dosage and Administration (2.2) ]. Drug Interactions Advise patients and caregivers to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products.

Inform patients to avoid St. John's wort, grapefruit, or grapefruit juice while taking HYRNUO [see Drug Interactions (7.1 , 7.2) ] .

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Sevabertinib pharmacokinetics were observed at steady state in patients with advanced NSCLC harboring activating HER2 or EGFR mutations at the approved recommended dosage and are presented as mean (CV%), unless otherwise specified. Sevabertinib maximum concentration (C max ) is 902 (45%) ng/mL and total systemic exposure (AUC) is 6,640 (50%) ng*h/mL. Sevabertinib C max and AUC increase in a dose-proportional manner across the dose range of 10 mg to 80 mg (0.25 to 2 times the approved recommended total daily dose).

Sevabertinib accumulation is approximately 1.7-fold for AUC and 1.3-fold for C max at the approved recommended dosage. Steady state is achieved within 3 days. Absorption Sevabertinib median (min, max) time to maximum concentrations (T max ) is approximately 2 hours (0.5, 8.2 hours) after a single dose.

Effect of Food Sevabertinib C max decreases by 56% and AUC decreases by 28% with a high-fat meal (1000 calories, 50% fat) in healthy subjects. No clinically significant differences in sevabertinib pharmacokinetics were observed following administration of a low-fat meal (400 calories, 25% fat). Distribution Sevabertinib apparent volume of distribution is 28 L (42%).

Sevabertinib plasma protein binding is 95%. The blood-to-plasma concentration ratio is 0.6. Elimination Sevabertinib effective half-life is approximately 8 hours (33%) with an apparent clearance of

3.1L/hour (38%). Metabolism Sevabertinib is primarily metabolized by CYP3A (major), CYP1A1 (minor), and glucuronidation (minor). Excretion After a single oral dose of radiolabeled sevabertinib 40 mg to healthy subjects, approximately 84% of the dose was recovered in feces (14% unchanged) and approximately 10% in urine (1.3% unchanged).

Specific Populations No clinically significant effects in the pharmacokinetics of sevabertinib were observed based on age (18 to 91 years), race (27% White, 65% Asian, 2.7% Black/African American), sex, body weight (29 to 155 kg), smoking status, eGFR 30 to < 90 mL/min, or mild hepatic impairment (AST > ULN and total bilirubin ≤ ULN; or total bilirubin >1 to 1.5× ULN and any AST). The effect of severe renal impairment (eGFR 15 to <30 mL/min), end-stage renal disease (eGFR <15 mL/min), moderate hepatic impairment (total bilirubin >1.5 to 3× ULN and any AST) or severe hepatic impairment (total bilirubin > 3× ULN and any AST) on sevabertinib pharmacokinetics is unknown.

Drug Interaction Studies Clinical Studies Strong CYP3A Inhibitors: Sevabertinib AUC increased 2.3-fold and C max 1.6-fold following concomitant use of itraconazole (strong CYP3A inhibitor) 200 mg once daily. Strong CYP3A Inducers: Sevabertinib AUC decreased by 79% and C max by 57% following concomitant use of carbamazepine (strong CYP3A inducer) 600 mg once daily. CYP3A Substrates: Midazolam (CYP3A substrate) AUC increased 2-fold and C max 1.8-fold following concomitant use of HYRNUO 20 mg twice daily.

P-gp Substrates: Dabigatran etexilate (P-gp substrate) AUC increased 1.4-fold following concomitant use of HYRNUO 20 mg twice daily. BCRP Substrates: Rosuvastatin (BCRP substrate) AUC increased 1.3-fold and C max 1.4-fold following concomitant use of HYRNUO 20 mg twice daily. Other Drugs: No clinically significant differences in sevabertinib pharmacokinetics were observed when used concomitantly with esomeprazole (proton pump inhibitor).

In Vitro studies CYP450 Enzymes: Sevabertinib inhibits CYP1A1 and CYP2C8 but does not inhibit CYP2A6, CYP2C9, CYP1A2, CYP2B6, CYP2D6, CYP2C19, or CYP2E1. Sevabertinib does not induce CYP1A2, CYP2B6, or CYP2C19. Transporter Systems: Sevabertinib is a substrate of P-gp, and BCRP.

Sevabertinib inhibits MATE1 and MATE2-K but does not inhibit OATP1B1, OATP1B3, MRP2, OAT1, OAT3, OCT1, or OCT2.

🧬 Pharmacodynamics 62 words ▾

12.2Pharmacodynamics Exposure-Response Relationship Higher sevabertinib exposure, across the dose range of 10 to 80 mg total daily dose (0.25 to 2 times the recommended dosage), was associated with an increased incidence of diarrhea (all grade and Grade ≥3) and rash. Cardiac Electrophysiology At 2 times the maximum recommended dose, a mean increase in the QTc interval >20 ms was not observed.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Locally Advanced or Metastatic Non-squamous NSCLC with HER2 TKD Activating Mutations The efficacy of HYRNUO was evaluated in SOHO-01 (NCT05099172), an open-label, single-arm, multicenter, multi-cohort clinical study. Eligible patients (Groups D and E) were required to have previously treated locally advanced or metastatic NSCLC with HER2 ( ERBB2 ) activating mutations and have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. HER2 ( ERBB2 ) activating mutations were determined in tumor tissue or plasma by local laboratories prior to enrollment.

Patients with treated, stable and asymptomatic brain metastases were eligible. Patients with symptomatic CNS metastases, clinically significant cardiac disease, and history of steroid dependent interstitial lung disease (ILD)/pneumonitis were excluded. Patients received HYRNUO 20 mg orally twice daily until disease progression or unacceptable toxicity.

The major efficacy outcomes were confirmed objective response rate (ORR) and duration of response (DOR), as assessed by Blinded Independent Central Review (BICR) using RECIST v1.1. The efficacy population included 70 patients from Group D, and 52 patients from Group E, with advanced non-squamous NSCLC with HER2 ( ERBB2 ) tyrosine kinase domain (TKD) activating mutations based on prospective local testing. Of the 122 patients in these combined cohorts, tumor tissue samples from 67.2% (82/122) of patients were retrospectively tested using Oncomine™ Dx Target Test (Life Technologies Corporation).

While 92.7% (76/82) of samples were positive for HER2 ( ERBB2 ) TKD activating mutations, 7.3% (6/82) were unevaluable, and there were no samples with negative status for HER2 ( ERBB2 ) TKD activating mutations. NSCLC Previously Treated, Naïve to HER2-Targeted Therapy: Group D Efficacy was evaluated in 70 patients with locally advanced or metastatic non-squamous NSCLC with HER2 ( ERBB2 ) TKD activating mutations who had received prior systemic therapy but were naïve to therapy targeting HER2 mutations. Baseline demographic and disease characteristics of the efficacy population were: median age 59 years (range 29 to 77 years); 67% female; 70% Asian, 23% White, 1.4% Black or African American, 6% race not reported; 2.9% were of Hispanic or Latino ethnicity.

Patients had an ECOG performance status of either 0 (39%) or 1 (61%); 69% were never-smokers, 29% were former smokers and 2.9% were current smokers. All patients had adenocarcinoma histology. Ninety-one percent (91%) of patients had stage IV disease and 20% had stable brain metastases.

The median number of prior therapies was 1 (range 1 to 8); 94% of patients received prior platinum-based chemotherapy, 71% received prior immunotherapy, and 69% received both in combination. Among the patients, 70% of patients had a Y772_A775dup (YVMA) exon 20 insertion. Efficacy results for SOHO-01 Group D are presented in Table 8.

Table 8: Efficacy Results for SOHO-01: Group D ORR 95% CI calculated using Clopper-Pearson method. Efficacy Parameter HYRNUO N=70 CI – Confidence Interval Objective Response Rate (ORR) , (95% CI) 71% (59, 82) Complete Response 2.9% Partial Response 69% Duration of Response (DOR) Observed proportion of responding patients with duration of response beyond landmark time. N=50 Median, months (95% CI) Kaplan-Meier estimate.

9.2(6.3, 15.0) DOR ≥6 months 54% DOR ≥12 months 18% NSCLC Previously Treated, Including Prior HER2 Targeted Antibody Drug Conjugates (ADCs): Group E Efficacy was evaluated in 52 patients with locally advanced or metastatic non-squamous NSCLC with HER2 ( ERBB2 ) TKD activating mutations who had received prior systemic therapy including HER2-targeted ADCs. Baseline demographic and disease characteristics of this efficacy population were: median age 65 years (range 35 to 91 years); 67% female; 62% Asian, 27% White, 6% Black or African American, 6% race not reported; 1.9% were of Hispanic or Latino ethnicity.

Patients had an… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 54 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies have not been conducted with sevabertinib. Mutagenesis Sevabertinib was not genotoxic in a bacterial reverse mutation (Ames) and an in vitro micronucleus assay, or an in vivo micronucleus assay in rats. Impairment of Fertility Fertility studies have not been conducted with sevabertinib.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 51 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies have not been conducted with sevabertinib. Mutagenesis Sevabertinib was not genotoxic in a bacterial reverse mutation (Ames) and an in vitro micronucleus assay, or an in vivo micronucleus assay in rats. Impairment of Fertility Fertility studies have not been conducted with sevabertinib.

📄 Patient Package Insert ~3 min read ▾

PATIENT INFORMATION HYRNUO ® (Her noo' oh) (sevabertinib) tablets, for oral use This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: 11/2025 What is HYRNUO?

HYRNUO is a prescription medicine that is used to treat adults with a type of lung cancer called non-small cell lung cancer (NSCLC) that: has spread within your chest or to other parts of the body, and has a certain abnormal human epidermal growth factor receptor 2 ( HER2 ) gene(s), and who have received a previous treatment (systemic therapy). Your healthcare provider will perform a test to make sure HYRNUO is right for you. It is not known if HYRNUO is safe and effective in children.

Before taking HYRNUO, tell your healthcare provider about all of your medical conditions, including if you: have liver problems. have lung or breathing problems other than lung cancer. are pregnant or plan to become pregnant. HYRNUO can harm your unborn baby. Females who are able to become pregnant: Your healthcare provider will do a pregnancy test before you start treatment with HYRNUO.

Use effective birth control (contraception) during treatment and for 1 week after the last dose of HYRNUO. Talk to your healthcare provider about birth control methods that may be right for you. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during your treatment with HYRNUO.

Males with female partners who are able to become pregnant: Use effective birth control (contraception) during treatment and for 1 week after your last dose of HYRNUO. Talk to your healthcare provider about birth control methods that may be right for you and your partner. are breastfeeding or plan to breastfeed. It is not known if HYRNUO passes into breast milk.

Do not breastfeed during treatment and for 1 week after the last dose of HYRNUO. Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. HYRNUO may affect the way other medicines work, and other medicines may affect how HYRNUO works.

Know the medicines you take. Keep a list of them with you to show to your healthcare provider and pharmacist when you get a new medicine. How should I take HYRNUO?

Take HYRNUO exactly as your healthcare provider tells you. Do not change your dose or stop taking HYRNUO unless your healthcare provider tells you to. Take HYRNUO 2 times a day with food.

Swallow HYRNUO tablets whole with a glass of water. Do not cut, crush or chew HYRNUO tablets. If you miss a dose of HYRNUO, take your prescribed dose as soon as you remember before the next scheduled dose.

Do not take 2 doses at the same time to make up for a missed dose. If you vomit after taking a dose of HYRNUO, do not make up the dose. Take your next dose at your regularly scheduled time.

What should I avoid while taking HYRNUO? Avoid eating grapefruit or drinking grapefruit juice during treatment with HYRNUO. Grapefruit may increase the amount of HYRNUO in your blood.

What are the possible side effects of HYRNUO? HYRNUO may cause serious side effects, including: diarrhea . Diarrhea is common and can be severe during treatment with HYRNUO and usually occurs in the first week of treatment.

Diarrhea can cause the loss of body fluids (dehydration) and salts (electrolyte imbalances). At the first signs of diarrhea (loose stool) or increased bowel movements, tell your healthcare provider right away, drink plenty of fluids and start treatment for diarrhea as soon as possible. You should have an anti-diarrhea medicine available before you start taking HYRNUO. liver problems.

HYRNUO can cause increases in liver blood tests which may be severe. Your healthcare provider will do blood tests to check your liver function before you start taking and during treatment with HYRNUO. Tell your healthcare provider right away if you develop any signs and symptoms of liver problems including: yellowing of the skin or white part of your eyes… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 68 words ▾

PRINCIPAL DISPLAY PANEL - 10 mg Tablet Bottle Label NDC 50419-397-01 HYRNUO ® (sevabertinib) tablets 10 mg Rx Only BAYER 120 film-coated tablets PRINCIPAL DISPLAY PANEL - 10 mg Tablet Bottle Label

PRINCIPAL DISPLAY PANEL - 10 mg Tablet Bottle Carton NDC 50419-397-01 Rx only HYRNUO ® (sevabertinib) tablets 10 mg — 120 film-coated tablets — Oral use BAYER PRINCIPAL DISPLAY PANEL - 10 mg Tablet Bottle Carton

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Hyrnuo — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Hyrnuo. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Total Part D spend
$482.7K
Claims incl. refills
24
Beneficiaries
14
Spend / beneficiary
$34,481.51
Spend / claim
$20,114.21
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Bayer HealthCare Pharmaceuticals Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Bayer HealthCare Pharmaceuticals Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 50419-0395-01 · Bayer 50419-0402-03 · Bayer →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.