Lirafugratinib's Sept 27 PDUFA Does Not Rewrite Pemazyre PAs or Lytgobi CDx

On March 30, 2026, Elevar Therapeutics announced that the U.S. Food and Drug Administration (FDA) accepted for Priority Review its New Drug Application (NDA) for lirafugratinib (RLY-4008), an investigational, oral fibroblast growth factor receptor 2 (FGFR2) selective tyrosine kinase inhibitor (TKI), setting a Prescription Drug User Fee Act (PDUFA) target action date of September 27, 2026.[1]

The proposed indication targets adult patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma (CCA) harboring FGFR2 gene fusions or other rearrangements. If approved, lirafugratinib would enter an oncology niche already shaped by two approved targeted oral therapies: Incyte's Pemazyre (pemigatinib; NDA 213736), which secured accelerated approval in April 2020, and Taiho Oncology's Lytgobi (futibatinib; NDA 214801), which received accelerated approval in September 2022.[2][3] A third agent, infigratinib (Truseltiq; NDA 214622), was granted accelerated approval in May 2021 but was formally withdrawn from the U.S. market in May 2024 after commercial and confirmatory trial challenges.[4]

For cancer center pharmacy and therapeutics (P&T) committees, health plan medical directors, and specialty pharmacy network managers, Elevar's upcoming September 27 regulatory action date presents critical formulary and utilization management decisions:

Can a health plan treat FDA's September 27 PDUFA clock, the ReFocus Phase 1/2 trial's 46.5 percent overall response rate (ORR), or preclinical FGFR2-selectivity claims as an immediate preferred product, as an automated rewrite of Pemazyre or Lytgobi prior authorization (PA) criteria, or as an established companion diagnostic code under FoundationOne CDx?

The direct operational answers across regulatory, clinical, diagnostic, and payer dimensions are clear:

A PDUFA target date is a review timetable, not a commercial approval: Elevar's March 30 announcement documents that FDA completed filing review and granted Priority Review.[1] That announcement is a sponsor press release, not a regulatory decision or coverage determination. As of September 4, 2026, a live Drugs@FDA search for the ingredient name lirafugratinib returns no matching application (API last updated September 2, 2026), and DailyMed contains no U.S. Structured Product Labeling (SPL). A raw token search for RLY-4008 is not an application match: it hits unrelated records because the API tokenizes the query. FDA may approve the application, issue a Complete Response Letter (CRL), or extend the review cycle under 21 CFR 314.60.
Incumbent FGFR2 inhibitors remain under Accelerated Approval: Live federal labeling for both Pemazyre (SPL setid 9e1f2222-1d89-4e63-989c-ccebe2ab1eb4, effective_time 20260609, version 17) and Lytgobi (SPL setid 0b1332a1-0581-4707-9bf6-1eccfa39bef4, effective_time 20251027, version 8) confirms that their cholangiocarcinoma indications remain accelerated, contingent upon verification and description of clinical benefit in confirmatory studies.[2][3] A third accelerated approval would not convert either incumbent to traditional approval or resolve the postmarketing requirement (PMR) burden.
Truseltiq's withdrawal highlights confirmatory trial vulnerability: On May 16, 2024, FDA withdrew approval of NDA 214622 after Helsinn, then the NDA holder, requested withdrawal under 21 CFR 314.150(d).[4][15] Helsinn cited difficulties enrolling the confirmatory first-line trial (the PROOF trial, NCT03773302) and concluded that continued second-line distribution was not commercially reasonable.[16] This precedent shows that single-arm accelerated approvals in a rare molecular subset remain reversible when confirmatory enrollment fails.
ReFocus trial data represent an abstract cutoff, not a comparative ranking: The clinical basis for lirafugratinib's NDA is the pivotal cohort of the Phase 1/2 ReFocus study (NCT04526106; actual enrollment 490, completed).[5] Data presented at the ASCO Gastrointestinal Cancers Symposium (published in Journal of Clinical Oncology, January 12, 2026) reported an Independent Review Committee (IRC)-assessed confirmed ORR of 46.5 percent (53/114; 95% CI: 37.1–56.1%) with a median duration of response (DOR) of 11.8 months, based on a September 27, 2024 data cutoff.[6] While conference prose rounded this to 47 percent, the audited table reports 46.5 percent. Cross-trial comparisons against Pemazyre's FIGHT-202 (36 percent ORR; median DOR 9.1 months) or Lytgobi's TAS-120-101 (42 percent ORR; median DOR 9.7 months) are single-arm snapshots that cannot establish statistical superiority.[2][3]
The ReFocus abstract does not report hyperphosphatemia rates: Preclinical data frame lirafugratinib as an FGFR2-selective inhibitor designed to spare FGFR1 (which mediates hyperphosphatemia) and FGFR4 (which mediates gastrointestinal toxicity). However, the ASCO GI 2026 abstract reports grade 3 or higher treatment-related adverse events (TRAEs) of palmar-plantar erythrodysesthesia (32.8 percent) and stomatitis (12.1 percent), but does not publish hyperphosphatemia incidence.[6] P&T committees cannot assume labeled phosphate safety until FDA publishes the final prescribing information and review memos.
Lirafugratinib does not inherit existing companion diagnostic approvals: Pemazyre's Section 1 and Section 2.1 explicitly require an "FDA-approved test" and point to FDA's CompanionDiagnostics listing. The concurrent registrational assay is FoundationOne CDx PMA P170019/S013, approved April 17, 2020—the same day as NDA 213736.[2][13] In sharp contrast, Lytgobi's Section 2.1 explicitly states that an FDA-approved test is not available, permitting local next-generation sequencing (NGS).[3] Lirafugratinib cannot automatically use FoundationOne CDx codes; unless FDA approves a specific premarket approval (PMA) supplement for lirafugratinib, plans enforcing strict companion diagnostic requirements will generate initial claims friction.
Public PAs enforce explicit brand steps, testing rules, and class exclusions: Federal Employee Program (FEP) Blue Policy 5.21.144 (effective April 1, 2026) requires an FDA-approved test, mandatory serum phosphate monitoring, and still lists withdrawn Truseltiq under related policies.[7] Neighborhood Health Plan of Rhode Island (NHPRI / Evolent UM-ONC_1398, effective July 26, 2024) enforces an explicit class exclusion against patients with prior FGFR2 inhibitor therapy (citing Lytgobi).[8] UnitedHealthcare Policy 2024 P 1399-3 covers Lytgobi for extrahepatic CCA beyond its labeled intrahepatic scope based on NCCN compendia.[9] A September 27 approval would not automatically rewrite these regional and commercial policies.

┌──────────────────────────────────────────────────────────────────────────────────────────────────┐
│              LIRAFUGRATINIB VS. APPROVED FGFR2 CCA TKIS & ACCESS SCORECARD                       │
├──────────────────────────┬──────────────────────────┬──────────────────────┬─────────────────────┤
│ Dimension                │ Lirafugratinib (RLY-4008)│ Pemazyre (NDA 213736)│ Lytgobi (NDA 214801)│
├──────────────────────────┼──────────────────────────┼──────────────────────┼─────────────────────┤
│ Developer / Sponsor      │ Elevar Therapeutics      │ Incyte Corporation   │ Taiho Oncology      │
│ FDA Regulatory Status    │ Priority Review NDA      │ Accelerated Approval │ Accelerated Approval│
│ Target / Action Date     │ PDUFA Sept 27, 2026      │ Approved 04/17/2020  │ Approved 09/30/2022 │
│ Labeled Indication Scope │ Pending (Pretreated CCA) │ Pretreated CCA & MLN │ Pretreated iCCA only│
│ Companion Diagnostic Gate│ No PMA approved to date  │ FDA-approved test req│ Explicitly "None"   │
│ Registered Pivotal Trial │ ReFocus (NCT04526106)    │ FIGHT-202 NCT02924376│ TAS-120-101 NCT02052│
│ Pivotal Population (n)   │ n=114 IRC FGFRi-naive    │ n=107 FGFR2 fusions  │ n=103 FGFR2 fusions │
│ Confirmed ORR (95% CI)   │ 46.5% (37.1%–56.1%)      │ 36% (27%–45%)        │ 42% (32%–52%)       │
│ Median DOR (months)      │ 11.8 mo (7.5–13.0)       │ 9.1 mo (6.0–14.5)    │ 9.7 mo (7.6–17.1)   │
│ Documented Labeled Risks │ Not labeled (abstract AEs)│ HyperP 93% lab, RPED│ HyperP, Ocular RPED │
│ Orange Book TE Code      │ Pending (No NME row)     │ BLANK (No AB generic)│ Blank; 4mg RS; 16mg DISCN│
│ Exclusivity Expiration   │ Pending review           │ ODE April 17, 2027   │ NCE Sept 30, 2027   │
│ FEP 5.21.144 Policy Role │ Not listed               │ Covered with CDx gate│ Not this Pemazyre PA│
│ NHPRI Prior-FGFR2 Barrier│ Subject to class exclude │ Denied if post-FGFR2 │ Explicit class note │
│ Medicaid NADAC 2026 Data │ 0 rows (Specialty Rx)    │ 0 rows (Specialty Rx)│ 0 rows (Specialty)  │
└──────────────────────────┴──────────────────────────┴──────────────────────┴─────────────────────┘

What Did FDA Accept on March 30 Versus What a Plan Can Treat as Labeled on September 4, and Which Document Is Still Missing?

Health system formulary committees and managed care pharmacy directors must clearly separate FDA's procedural acceptance of a regulatory dossier from the statutory establishment of an approved drug product.

The Procedural Scope of the March 30 Priority Review

On March 30, 2026, Elevar Therapeutics publicly disclosed that FDA completed its filing review and accepted the NDA for lirafugratinib for the treatment of patients with cholangiocarcinoma harboring FGFR2 fusions or other rearrangements who have received prior systemic therapy.[1]

Under the Prescription Drug User Fee Act performance goals, FDA granted Priority Review, which establishes a six-month target review clock from filing, resulting in the September 27, 2026 PDUFA target action date.[1] Elevar's release restates FDA's Priority Review criterion: designations go to applications that, if approved, would provide a significant improvement in the safety or effectiveness of the treatment of a serious condition. Priority Review is a PDUFA timetable, not Fast Track, Breakthrough Therapy, or accelerated approval under Section 506 of the FD&C Act.

However, clinical and commercial teams must account for what this designation does not constitute:

It is not an approval: A PDUFA date is an internal agency administrative deadline for completing the initial review cycle. FDA is under no statutory obligation to grant marketing approval on that date. The agency may issue a Complete Response Letter under 21 CFR 314.125 detailing clinical, pharmacology, or Current Good Manufacturing Practice (CGMP) deficiencies.
It does not guarantee standard action: Under 21 CFR 314.60, the submission of a major amendment—such as updated safety analyses, revised stability batches, or substantial clinical trial re-analyses—can automatically trigger a three-month PDUFA clock extension.
It conveys zero coverage entitlement: Prior to formal FDA approval and the publication of official prescribing information, medical and pharmacy benefit plans cannot establish active reimbursement codes, add the drug to formularies, or adjudicate prior authorization requests.

Live Regulatory Verification: The Missing Federal Documents

As of September 4, 2026, direct queries of official federal databases confirm that lirafugratinib remains entirely investigational:

Drugs@FDA Database: The live Drugs@FDA API (last updated September 2, 2026) returns no matches for the ingredient name lirafugratinib.[10] There is no application whose brand or generic name is lirafugratinib or RLY-4008. A raw RLY-4008 token search is not evidence of a posted NME row; it surfaces unrelated applications because the API tokenizes the query. In contrast, Drugs@FDA indexes full regulatory documentation for NDA 213736 (Pemazyre; approved April 17, 2020) and NDA 214801 (Lytgobi; approved September 30, 2022).
National Library of Medicine / DailyMed: A search of the DailyMed repository confirms that zero Structured Product Labeling files exist for lirafugratinib. There is no federally validated text defining indications, contraindications, boxed warnings, dosing schedules, or dose modification tables.
FDA CDER New Molecular Entity (NME) Calendar: FDA's Novel Drug Approvals for 2026 page (content current September 3, 2026) lists 37 approved novel therapies year-to-date, including Zanvastro (zilganersen; NME 37, approved September 3, 2026). Lirafugratinib is not an approved NME.

Consequently, until FDA issues an approval letter and posts the approved label, P&T committees have no binding federal source document defining the exact labeled population, whether the approval is accelerated or traditional, whether an FDA-approved companion diagnostic is mandated, or what postmarketing confirmatory commitments are imposed.

Do Live Pemazyre and Lytgobi Labels Still Say Accelerated Approval, and What Did FDA Actually Withdraw When Truseltiq Left the Market?

A frequent misconception among market access observers is that because Pemazyre was approved over six years ago in 2020 and Lytgobi in 2022, they have transitioned to full, traditional approval. Official labeling confirms that both drugs remain tethered to the accelerated approval pathway, creating a delicate regulatory baseline for any incoming third market entrant.

Live Originator Labeling Analysis: Section 1 Accelerated Status

Direct extraction of active Structured Product Labeling reveals that both approved oral FGFR2 inhibitors remain subject to statutory accelerated approval restrictions:

Pemazyre (NDA 213736): The active openFDA and DailyMed SPL (setid 9e1f2222-1d89-4e63-989c-ccebe2ab1eb4, effective_time 20260609, version 17) includes two distinct labeled indications in Section 1. While Section 1.2 covers relapsed or refractory myeloid/lymphoid neoplasms (MLN) with FGFR1 rearrangement (approved via Priority Review Supplement 2 on August 26, 2022), Section 1.1 for cholangiocarcinoma maintains the original accelerated approval language:

"PEMAZYRE is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test... This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)."[2]

Section 5.2 of the same SPL states that among patients who received a starting dose of Pemazyre 13.5 mg across clinical trials, hyperphosphatemia was reported in 93 percent based on laboratory values above the upper limit of normal. Section 5.1 states that RPED occurred in 11 percent of 635 patients who started 13.5 mg, including Grade 3–4 RPED in 1.3 percent. Those are labeled pemigatinib rates, not a ranking versus lirafugratinib or Lytgobi.[2]

Lytgobi (NDA 214801): The active SPL (setid 0b1332a1-0581-4707-9bf6-1eccfa39bef4, effective_time 20251027, version 8) similarly retains strict accelerated approval language in Section 1:

"LYTGOBI is indicated for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements... This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)."[3]

Crucially, Lytgobi's labeled indication is restricted specifically to intrahepatic cholangiocarcinoma (iCCA), whereas Pemazyre's label encompasses all cholangiocarcinomas regardless of anatomical origin (intrahepatic, perihilar, or distal).

The Truseltiq Precedent: Accelerated Approval and Confirmatory Trial Failure

The operational vulnerability of accelerated approvals in biomarker-defined cholangiocarcinoma is demonstrated by the regulatory history of Truseltiq (infigratinib; NDA 214622).

On May 28, 2021, FDA granted accelerated approval to infigratinib (Truseltiq, QED Therapeutics, Inc.) for previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement as detected by an FDA-approved test, based on an ORR of 23 percent (95% CI: 16–32) and median duration of response of 5 months (95% CI: 3.7–9.3) in a 108-patient cohort.[4] FDA also approved FoundationOne CDx as a companion diagnostic for that use.[4][13] As a condition of accelerated approval under Section 506(c) of the FD&C Act, the sponsor was required to conduct postmarketing trials to verify clinical benefit. The confirmatory study listed on ClinicalTrials.gov is NCT03773302, titled the PROOF trial: a Phase 3 comparison of oral infigratinib versus gemcitabine plus cisplatin in first-line FGFR2-altered advanced cholangiocarcinoma, sponsored by QED Therapeutics, a BridgeBio company, and now terminated.[16]

However, on May 16, 2024, FDA withdrew approval of NDA 214622. The Federal Register notice (89 FR 42887) records that Helsinn Healthcare SA, then the NDA holder, requested withdrawal under 21 CFR 314.150(d) and waived its opportunity for a hearing.[4][15] FDA's withdrawn-approval page states:

"The sponsor voluntarily requested withdrawal of infigratinib. The sponsor's request cited difficulties in recruiting and enrolling study subjects for the required confirmatory clinical trial in first line cholangiocarcinoma (a new indication under investigation for TRUSELTIQ), and the determination that, as a result, continued distribution of TRUSELTIQ in second line cholangiocarcinoma (the accelerated approval indication) was not commercially reasonable."[4]

The withdrawal of Truseltiq carries three profound implications for health plans and oncology clinicians:

Confirmatory enrollment in a rare biomarker subset is difficult: FGFR2 fusions or rearrangements are confined to a molecular subset of intrahepatic cholangiocarcinoma. A front-line randomized Phase 3 trial against standard chemotherapy (or modern regimens such as gemcitabine/cisplatin plus durvalumab) has to compete for that constrained pool against commercially available second-line oral TKIs. FDA's withdrawal page and Helsinn's letter treat that enrollment failure as the reason second-line distribution was no longer commercially reasonable; they do not publish an incidence rate, and this article does not invent one.
Accelerated approval is reversible: Payers recognize that accelerated approvals supported solely by single-arm Phase 2 response rates carry tangible regulatory risk. If confirmatory postmarketing requirements cannot be met, FDA will facilitate withdrawal.
Payer policies lag federal withdrawals: As detailed below, major commercial and federal payer policies continued to list Truseltiq under active coverage criteria or related policies years after FDA announced its final withdrawal.

Which Public PAs Already Require an FDA-Approved FGFR2 Test, Phosphate Monitoring, or No Prior FGFR2 Inhibitor, and Which Still Name Truseltiq?

To evaluate how an FDA approval of lirafugratinib would be received by the market access apparatus, analysts must review current commercial and public prior authorization policies governing oral FGFR2 inhibitors.

FEP Blue Policy 5.21.144: Strict Testing Gates and Stale Policy Links

The Blue Cross Blue Shield Association's Federal Employee Program (FEP) maintains one of the most structured public oncology formularies in the United States. FEP Blue Pharmacy Policy 5.21.144 (covering Pemazyre; last reviewed March 6, 2026, effective April 1, 2026) outlines rigorous clinical prerequisites before coverage is approved.[7]

To secure authorization for Pemazyre in cholangiocarcinoma under FEP Blue, the submitted clinical record must meet the policy's prior-approval requirements:

Age Threshold: Patient must be 18 years of age or older.
Disease Stage: Documentation of unresectable locally advanced or metastatic cholangiocarcinoma.
Prior Systemic Therapy: Patient must have received at least one prior systemic therapy regimen (confirming second-line or subsequent positioning).
Diagnostic Specification: The tumor must harbor an FGFR2 fusion or other rearrangement as detected by an FDA-approved test.[7]
Baseline Ophthalmic Evaluation: Documentation that a baseline ophthalmological examination has been done and that the patient will be monitored for retinal pigment epithelial detachment (RPED). The policy background quotes Pemazyre's labeled monitoring schedule—including optical coherence tomography (OCT) before initiation, every two months for the first six months, and every three months thereafter—but that schedule is PI language reproduced in the rationale, not a separately numbered coverage checkbox beyond the baseline-exam-and-monitor requirement.[2][7]
Serum Phosphate Monitoring: Prescriber agreement to monitor for hyperphosphatemia and to initiate a low-phosphate diet or phosphate-lowering therapy as clinically indicated.[7]

Under FEP Blue 5.21.144, the prior-approval duration is 12 months, with renewal requiring no disease progression or unacceptable toxicity plus continued RPED and phosphate monitoring. The policy enforces a quantity limit of 56 tablets per 84 days for cholangiocarcinoma (versus 84 tablets per 84 days for myeloid/lymphoid neoplasms)—a quantity that matches Pemazyre's labeled 21-day CCA cycle of 14 days of once-daily oral dosing followed by 7 days off treatment, not a reader dosing instruction.[2][7]

Critically, under the "Related Policies" header, FEP 5.21.144 explicitly references:

"Related policies: Truseltiq"[7]

This reference, active through the April 1, 2026 revision, illustrates the pronounced administrative lag in payer policy maintenance: FEP's policy infrastructure continues to index a separate pharmacy guideline for a product that was formally withdrawn by FDA in May 2024.

NHPRI / Evolent UM-ONC_1398: The Class Exclusion Barrier

Regional health plans and oncology benefit managers (OBMs) frequently enforce utilization management edits designed to prevent sequential, off-label cycling of targeted therapies.

Neighborhood Health Plan of Rhode Island (NHPRI), utilizing clinical criteria managed by Evolent Health (Policy UM-ONC_1398, approved July 10, 2024, effective July 26, 2024; covering Commercial, Exchange, and Medicaid lines), governs pemigatinib coverage.[8] While the policy permits diagnostic documentation from "Foundation One CDX or another gene sequencing test," Section II (Exclusion Criteria) establishes a critical class barrier:

"Disease progression while receiving Pemazyre (pemigatinib) or on prior FGFR2 inhibitor therapy [e.g., Lytgobi (futibatinib)]."[8]

This explicit restriction establishes a major commercial hurdle for lirafugratinib:

If an oncology P&T committee classifies lirafugratinib under an existing FGFR2-inhibitor class policy, patients whose disease progressed on first-line systemic chemotherapy followed by second-line Pemazyre or Lytgobi are excluded under that current criterion from receiving subsequent lirafugratinib unless the plan rewrites the exclusion.
Although Elevar's ReFocus trial included a specific exploratory cohort (Group 1) evaluating lirafugratinib in patients who had received prior FGFR inhibitors, standard commercial PAs do not authorize sequential FGFR2 inhibitor use without explicit trial-specific language or compendia listing.
Until plans actively rewrite their exclusion rules to carve out lirafugratinib, claims submitted for patients with prior FGFRi exposure will face automated prior authorization rejections under existing class policies.

UnitedHealthcare Clinical Pharmacy Program 2024 P 1399-3: Compendia vs. Label Scope

UnitedHealthcare's Pharmacy Clinical Pharmacy Program guideline for Lytgobi (2024 P 1399-3, approved November 2024, effective February 15, 2025) demonstrates how commercial payers expand or contract label boundaries using national oncology guidelines.[9]

While FDA's approved Section 1 indication for Lytgobi is strictly limited to intrahepatic cholangiocarcinoma, UHC's coverage criteria state:

"LYTGOBI is proven and medically necessary for the treatment of unresectable, resected gross residual, or metastatic cholangiocarcinoma (intrahepatic or extrahepatic) when all of the following criteria are met: 1. Tumor is positive for fibroblast growth factor receptor 2 (FGFR2) gene fusion or other rearrangement; and 2. Disease is second-line or subsequent; and 3. Prescribed by or in consultation with an oncologist."[9]

UHC's rationale explicitly cites the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Biliary Tract Cancers, which recommend futibatinib for both intrahepatic and extrahepatic disease. For lirafugratinib, whether FDA's eventual label specifies intrahepatic or broad cholangiocarcinoma will determine whether the drug requires an off-label NCCN compendia listing to achieve broad commercial access across both anatomical sub-types.

Specialty Pharmacy Channel and NADAC Realities

All approved oral FGFR2 inhibitors are distributed exclusively through restricted specialty pharmacy networks (such as Biologics by McKesson, Onco360, and manufacturer-contracted hubs).

An audit of the official Centers for Medicare & Medicaid Services (CMS) Medicaid National Average Drug Acquisition Cost (NADAC) 2026 datastore (dataset fbb83258-11c7-47f5-8b18-5f8e79f7e704) yields 0 rows for PEMAZYRE, PEMIGATINIB, LYTGOBI, and FUTIBATINIB.[11] Because these therapies bypass the retail community pharmacy channel and operate under limited distribution contracts, retail acquisition surveys do not capture their pricing. Lirafugratinib will similarly launch as an oral specialty drug, where copay assistance programs, bridge supplies, and specialty hub navigation—rather than retail discount programs or Part B buy-and-bill mechanics—dictate real-world patient access.

Why Does Pemazyre's Label Point to CompanionDiagnostics While Lytgobi's Label Says an FDA-Approved Test Is Not Available, and Would a Third TKI Inherit FoundationOne Codes?

A central point of friction in precision oncology prior authorization is the regulatory status of the biomarker assay used to identify the genomic alteration. In cholangiocarcinoma, FDA has established two diametrically opposed precedent frameworks across the incumbent drugs.

┌──────────────────────────────────────────────────────────────────────────────────────────────────┐
│             COMPANION DIAGNOSTIC REGULATORY ARCHITECTURE: PEMAZYRE VS. LYTGOBI                   │
├──────────────────────────┬──────────────────────────────────────┬────────────────────────────────┤
│ Feature                  │ Pemazyre (NDA 213736)                │ Lytgobi (NDA 214801)           │
├──────────────────────────┼──────────────────────────────────────┼────────────────────────────────┤
│ Prescribing Info Sec 1   │ "as detected by an FDA-approved test"│ "harboring FGFR2 fusions/rearr"│
│ Prescribing Info Sec 2.1 │ Directs to FDA CompanionDiagnostics  │ Explicitly states "None exists"│
│ Federal Register / PMA   │ FoundationOne CDx (P170019/S013)    │ None; local CLIA NGS permitted │
│ Diagnostic Coding Barrier│ Requires proof of FDA-approved test  │ Accepts broader NGS panel data │
│ Payer Denial Risk        │ High if local LDT or non-CDx assay   │ Minimal test-platform friction │
│ Lirafugratinib Impact    │ Lirafugratinib cannot inherit F1CDx  │ Could adopt "no CDx" approach  │
└──────────────────────────┴──────────────────────────────────────┴────────────────────────────────┘

The Regulatory Divide: Pemazyre's CDx Mandate vs. Lytgobi's Open Label

The statutory framework governing in vitro diagnostics (IVDs) under 21 CFR 814 requires FDA to review and approve a companion diagnostic when the use of a diagnostic device is essential for the safe and effective use of a therapeutic product.

Pemazyre's Closed System: When FDA approved Pemazyre on April 17, 2020, the agency simultaneously approved Foundation Medicine's FoundationOne CDx PMA supplement P170019/S013 as a companion diagnostic to identify cholangiocarcinoma patients with FGFR2 fusions and select rearrangements who may benefit from pemigatinib.[13] P170019/S016 is a different supplement, approved June 16, 2020, for tumor mutational burden and pembrolizumab—not Pemazyre. Section 2.1 of Pemazyre's labeling commands:

"Select patients for the treatment of unresectable locally advanced or metastatic cholangiocarcinoma with PEMAZYRE based on the presence of an FGFR2 fusion or other rearrangement in tumor specimens. Information on FDA-approved tests for the detection of FGFR2 fusions or other rearrangements in cholangiocarcinoma is available at: http://www.fda.gov/CompanionDiagnostics."[2]
Lytgobi's Open Architecture: When FDA approved Lytgobi on September 30, 2022, no companion diagnostic was approved concurrently. Instead, Section 2.1 of Lytgobi's labeling states:

"Select patients for the treatment of locally advanced or metastatic intrahepatic cholangiocarcinoma with LYTGOBI based on the presence of an FGFR2 gene fusion or other rearrangement... An FDA-approved test for detection of FGFR2 gene fusions or other rearrangements for selecting patients for treatment with LYTGOBI is not available."[3]

As analyzed in our previous research on labels without a companion diagnostic requirement, an explicit statement that no FDA-approved test exists provides legal and regulatory clearance for community oncologists to use comprehensive genomic profiling (CGP) from any CLIA-certified laboratory (including Tempus, Caris, Guardant, or internal hospital NGS panels).

Can Lirafugratinib Inherit FoundationOne CDx Codes?

The short answer is no.

As documented in our comprehensive census of FoundationOne CDx PMA supplements, companion diagnostic approvals are granted through specific, data-supported PMA supplement filings under Section 515 of the FD&C Act. A companion diagnostic label is strictly drug-specific and indication-specific. Table 1 of the FoundationOne CDx package insert enumerates the specific drug claims authorized by FDA.

While FoundationOne CDx holds an approved claim for Pemazyre in cholangiocarcinoma, it does not hold a class-wide approval for all FGFR2 inhibitors.
Infigratinib (Truseltiq) required its own separate PMA supplement, P170019/S021, approved May 28, 2021—the same day as NDA 214622—to be listed on the FoundationOne CDx label for FGFR2 fusion/rearrangement cholangiocarcinoma.[13]
Unless Foundation Medicine or Elevar submits a PMA supplement containing bridging study data that validates FoundationOne CDx as the registrational assay for lirafugratinib, lirafugratinib will launch without an approved companion diagnostic.

The Prior Authorization Mismatch Risk

This diagnostic distinction has direct, real-world consequences for patient access:

If a health plan's policy template mirrors FEP Blue 5.21.144—requiring that the tumor alteration be confirmed specifically by an "FDA-approved test"—patients tested via academic medical center NGS, liquid biopsy (cell-free DNA), or alternative tissue panels will face immediate claim denials. As detailed in our analysis of companion diagnostic mismatch denials, medical directors regularly issue technical denials when a patient has a verified FGFR2 fusion documented by an institutional panel that lacks federal premarket approval.

If FDA approves lirafugratinib under the Lytgobi precedent (stating that an FDA-approved test is not available), plans will be forced to adjust their policy logic to accept all CLIA-validated NGS reports.

Does ReFocus202 (NCT07359820) in Non-CCA Solid Tumors Change CCA Coverage If the September 27 Clock Is for Cholangiocarcinoma Only?

In modern oncology SERP queries, algorithmic search features and artificial intelligence overviews frequently conflate pipeline trials across different organ systems. A prominent example occurs in searches for lirafugratinib FDA, where a ClinicalTrials.gov result can point to NCT07359820 rather than the completed cholangiocarcinoma trial.[12]

Managed care analysts must clearly demarcate the boundaries between these two protocols:

┌──────────────────────────────────────────────────────────────────────────────────────────────────┐
│                 ELEVAR LIRAFUGRATINIB CLINICAL TRIAL PORTFOLIO COMPARISON                        │
├──────────────────────────┬──────────────────────────────────────┬────────────────────────────────┤
│ Parameter                │ ReFocus (NCT04526106)                │ ReFocus202 (NCT07359820)       │
├──────────────────────────┼──────────────────────────────────────┼────────────────────────────────┤
│ Study Name               │ First-in-Human / Phase 1/2 ReFocus   │ Phase 2 ReFocus202 Solid Tumors│
│ Target Disease Scope     │ Cholangiocarcinoma (CCA) & others    │ Non-CCA Solid Tumors ONLY      │
│ Cholangiocarcinoma Status│ Primary registrational cohorts       │ EXPLICITLY EXCLUDED            │
│ Study Status             │ COMPLETED (Actual enrollment 490)    │ RECRUITING (Estimated 30 pts)  │
│ First Posted / Start Date│ September 2020 (Completed Feb 2026)  │ Started June 4, 2026           │
│ Primary Regulatory Role  │ Basis for September 27, 2026 NDA     │ Exploratory basket pipeline    │
│ Commercial Benefit Impact│ Governs upcoming PDUFA decision      │ Cannot support CCA coverage    │
└──────────────────────────┴──────────────────────────────────────┴────────────────────────────────┘

NCT07359820 is an open-label, multi-center Phase 2 basket trial initiated on June 4, 2026 (last updated September 3, 2026), designed to assess the safety and efficacy of lirafugratinib in previously treated advanced or metastatic solid tumors harboring FGFR2 fusions or rearrangements, excluding cholangiocarcinoma (e.g., gastric cancer, breast cancer, colorectal cancer, non-small cell lung cancer, and urothelial carcinoma).[12]

Health plans must note the following governance boundaries:

The September 27 PDUFA review is strictly for cholangiocarcinoma: Elevar's NDA submitted under Priority Review is supported exclusively by the pivotal cholangiocarcinoma cohort from the completed ReFocus study (NCT04526106).
ReFocus202 cannot be cited to justify tumor-agnostic coverage: Payers will not authorize off-label reimbursement for non-biliary solid tumors based on the upcoming PDUFA date. Tumor-agnostic approvals (such as pembrolizumab for MSI-H/dMMR or larotrectinib for NTRK fusions) require comprehensive multi-tumor dossiers evaluated under specific FDA accelerated approval criteria.
Clinical cross-contamination: Formulary reviewers must disregard SERP listings or automated clinical summaries that cite ReFocus202 when evaluating the efficacy or safety package for biliary tract disease.

What Does ReFocus Actually Show: Auditing the Clinical Data Package and Safety Nuances

To assess whether lirafugratinib represents a genuine therapeutic advance or an incremental addition to the FGFR2 armamentarium, P&T committees must inspect the audited clinical trial evidence published to date.

The Pivotal Cohort: ReFocus Data from ASCO GI 2026

The primary clinical data package supporting Elevar's NDA was presented at the ASCO Gastrointestinal Cancers Symposium in January 2026 and published in the Journal of Clinical Oncology (Hollebecque et al., J Clin Oncol 2026;44[suppl 2]:476; online publication January 12, 2026).[6]

The pivotal cohort evaluated oral lirafugratinib at the ReFocus protocol dose of 70 mg once daily—a trial regimen, not a U.S. labeled dose—in patients with advanced or metastatic cholangiocarcinoma harboring FGFR2 gene fusions or rearrangements who were previously treated with at least one line of systemic therapy and were FGFR-inhibitor naive.[6]

Key audited parameters from the JCO publication include:

Efficacy Population (n): A total of 116 patients were enrolled. The primary efficacy analysis set evaluated by an Independent Review Committee (IRC) comprised n=114 patients (two patients were excluded from the IRC analysis because baseline imaging scans were not available for independent verification).[6]
Data Cutoff: The reported analyses reflect a clinical data cutoff of September 27, 2024 (exactly two years prior to the PDUFA target date).
Objective Response Rate (ORR):
- Confirmed IRC-assessed ORR was 46.5% (53/114; 95% CI: 37.1%–56.1%).
- Complete Response (CR): 2.6% (n=3).
- Partial Response (PR): 43.9% (n=50).
- Editorial Note: While the narrative text of the conference abstract rounds this figure to 47 percent, institutional P&T monographs and dossier submissions must cite the exact table value of 46.5 percent.[6]
Disease Control Rate (DCR): 96.5% (110/114; 95% CI: 91.3%–99.0%).
Duration of Response (DOR): Median DOR was 11.8 months (95% CI: 7.5–13.0 months).
Progression-Free Survival (PFS): Median PFS was 11.3 months (95% CI: 9.2–14.8 months).
Overall Survival (OS): Median OS reached 22.8 months (95% CI: 17.3–27.2 months).

Cross-Trial Comparison Is Not Clinical Superiority

In pharmaceutical commercialization, there is an inevitable temptation to juxtapose single-arm response rates to claim product superiority:

Lirafugratinib (ReFocus): 46.5% ORR; median DOR 11.8 months.[6]
Futibatinib (Lytgobi / TAS-120-101): 42% ORR; median DOR 9.7 months.[3]
Pemigatinib (Pemazyre / FIGHT-202): 36% ORR; median DOR 9.1 months.[2]

Managed care pharmacy directors and clinical pharmacologists must reject these comparisons as statistically ungrounded:

Differing Baseline Characteristics: Patient cohorts across FIGHT-202, TAS-120-101, and ReFocus varied widely in prior lines of therapy, proportion of patients with intrahepatic versus extrahepatic disease, baseline performance status, and post-progression therapies.
Confidence Interval Overlap: The 95% confidence intervals across all three trials substantially overlap (ReFocus: 37.1%–56.1%; TAS-120-101: 32%–52%; FIGHT-202: 27%–45%). None of these trials demonstrate a statistically significant difference in response rate.
Lack of Head-to-Head Evidence: There has never been a randomized clinical trial comparing one FGFR inhibitor against another. Cross-trial comparisons cannot justify preferential formulary placement, tiering advantages, or restrictive step therapy.

Toxicity Profile: Hand-Foot Syndrome, Stomatitis, and the Hyperphosphatemia Question

Preclinical discovery publications have framed lirafugratinib as an FGFR2-selective inhibitor designed to spare FGFR1 and FGFR4. Because FGFR1 inhibition in the renal proximal tubule suppresses urinary phosphate excretion—causing class-wide hyperphosphatemia that requires frequent lab monitoring and phosphate binders—the hypothesis was that an FGFR2-selective agent would eliminate hyperphosphatemia. That hypothesis is not a labeled claim.

However, the audited clinical evidence from the ASCO GI 2026 abstract reveals a distinct on-target toxicity profile:

Treatment-Related Adverse Events (TRAEs): Common grade 3 or higher TRAEs included:
- Palmar-plantar erythrodysesthesia (PPE / Hand-Foot Syndrome): 32.8% grade 3 or higher.[6]
- Stomatitis / Oral Mucositis: 12.1% grade 3 or higher.[6]
Dose Modifications: High rates of cutaneous and mucosal toxicity necessitated frequent dose adjustments:
- TRAE-related dose reductions: 75.9% of patients.[6]
- TRAE-related dose interruptions: 82.8% of patients.[6]
- TRAE-related permanent discontinuations: 4.3% of patients.[6]
The Critical Missing Lab Rate: Crucially, the published ASCO GI abstract does not report hyperphosphatemia incidence or grade distribution.[6]

While the low discontinuation rate (4.3 percent) suggests manageable chronic dosing, the reality that more than three-quarters of patients required dose reduction and more than 80 percent required dose interruption demonstrates substantial clinical management friction.

Most importantly, until FDA publishes the full prescribing information, clinicians and payers cannot assume that lirafugratinib is free from hyperphosphatemia or that FDA will omit serum phosphate monitoring directives from Section 2 and Section 5 of the label.

Orange Book Architecture and Exclusivity Timelines

A search of the FDA Orange Book confirms that generic erosion will not alter this market space in the near term:

Pemazyre (NDA 213736): Listed in 4.5 mg, 9 mg, and 13.5 mg strengths. All strengths carry a blank therapeutic equivalence (TE) code (meaning no generic equivalent is approved). Listed patents run through October 3, 2040, including compound patent 9,611,267 (expiring January 30, 2035) and method of use patent 10,131,667 (expiring April 17, 2034 with use code U-2809). Orphan Drug Exclusivity (ODE-292) protects the cholangiocarcinoma indication through April 17, 2027, and ODE-404 protects the MLN indication through August 26, 2029.[14]
Lytgobi (NDA 214801): The 4 mg tablet is listed as Prescription, RLD Yes, RS Yes, with a blank TE code. New Chemical Entity (NCE) exclusivity protects the drug through September 30, 2027, and ODE-410 extends through September 30, 2029. Listed patents extend to November 5, 2039.[14]
- Orange Book SKU Anomaly: The Orange Book lists Lytgobi's 16 mg tablet strength (approved July 28, 2025) as Discontinued (Marketing Status: Discontinued; RLD Yes, RS No). However, the live Lytgobi SPL (version 8, effective_time 20251027) still includes text in Section 2.2 describing dosing as either five 4 mg tablets or one 16 mg tablet plus one 4 mg tablet.[3][14]

Because both incumbents maintain robust patent thickets and orphan exclusivity through 2027–2029, lirafugratinib's market entry represents a brand-versus-brand specialty tier competition, with zero generic competition on the near-term horizon.

Which Existing PharmaDossier Pages Own CDx PMA Supplements, CDx-Denial Workflows, HER2 Biliary-Tract Access, No-CDx Labels, Orange Book Blanks, and PDUFA-Versus-PA Clocks, and Must Not Be Rewritten Here?

To preserve modular editorial reporting across the publication, this dossier applies established regulatory and reimbursement mechanisms without duplicating core analyses:

PMA Supplement Architecture: For an exhaustive analysis of how FDA reviews companion diagnostics and how PMA supplements expand across new drug indications, see our census of FoundationOne CDx PMA supplements.
Prior Authorization Denial Workflows: For an operational roadmap detailing how health plans adjudicate biomarker mismatch claims when a non-CDx assay is submitted, refer to our guide on CDx mismatch denials.
Biliary Tract Cancer Access: For coverage of targeted therapies and HER2-directed biologics in advanced biliary tract cancer, see our analysis of HER2 biliary-tract access.
Labels Lacking CDx Requirements: For an evaluation of small-molecule oncology therapies whose FDA prescribing information omits companion diagnostic requirements, refer to our explainer on labels without a companion diagnostic requirement.
PDUFA Clocks vs. Payer Criteria: For an examination of why an upcoming PDUFA date does not alter existing, restrictive plan prior authorizations, see our analysis of why PDUFA does not rewrite current PAs.
Orange Book Blank TE Ratings: For the statutory rules governing unrated originator listings and therapeutic equivalence evaluations, consult our tutorial on Orange Book blank TE codes.

Frequently Asked Questions

Is lirafugratinib FDA-approved today?

No. As of September 4, 2026, lirafugratinib (RLY-4008) is an investigational agent. It has no entry in Drugs@FDA, no application number posted in public directories, and no Structured Product Labeling (SPL) published on DailyMed.[10] Elevar Therapeutics announced on March 30, 2026, that FDA accepted its NDA for Priority Review and established a PDUFA target action date of September 27, 2026.[1] That date is an agency target for completing review, not a guarantee of marketing approval.

Does a Priority Review PDUFA date rewrite FEP Pemazyre criteria or UHC Lytgobi extrahepatic language?

No. Health plan medical policies and pharmacy formularies—such as FEP Blue 5.21.144 and UnitedHealthcare 2024 P 1399-3—are governed by formal P&T review cycles, published FDA labels, and established compendia (such as NCCN).[7][9] Payers do not modify coverage criteria, alter quantity limits, or open formulary tiers based on an upcoming PDUFA date. Even after approval, coverage criteria change only when a plan's P&T cycle rewrites the PDF.

Can a plan treat ReFocus 46.5 percent ORR as proof that lirafugratinib is more effective than Pemazyre or Lytgobi?

No. The 46.5 percent ORR reported from the ReFocus study (Hollebecque et al., J Clin Oncol 2026;44[suppl 2]:476) derives from a single-arm, open-label Phase 1/2 trial with an Independent Review Committee evaluation of 114 FGFRi-naive patients, based on a September 27, 2024 data cutoff.[6] There are no head-to-head randomized trials comparing lirafugratinib to Pemazyre (FIGHT-202; 36 percent ORR) or Lytgobi (TAS-120-101; 42 percent ORR).[2][3] Because confidence intervals overlap and baseline patient populations differ, cross-trial comparisons cannot support claims of clinical superiority.

If Truseltiq was withdrawn after confirmatory enrollment failed, does that mean a third FGFR2 CCA accelerated file is automatically denied?

No. FDA evaluates each New Drug Application independently based on the safety and efficacy evidence presented in the filing. However, Truseltiq's withdrawal on May 16, 2024—after Helsinn requested withdrawal under 21 CFR 314.150(d) because it could not enroll the confirmatory PROOF trial (NCT03773302) in first-line cholangiocarcinoma—demonstrates the postmarketing burden facing accelerated approvals in this disease.[4][15][16] FDA will subject Elevar's proposed confirmatory trial design and postmarketing commitments to intense scrutiny.

Evidence & Methodological Limitations

Regulatory Status Bounds: Analysis reflects primary documentation available as of September 4, 2026. Because FDA has not yet rendered a decision, final labeling, approved indications, boxed warnings, dosing tables, and postmarketing requirements remain subject to change.
Clinical Trial Data Limitations: Clinical findings for lirafugratinib are derived from the published ASCO GI 2026 meeting abstract (Hollebecque et al., J Clin Oncol 2026;44[suppl 2]:476) reflecting a data cutoff of September 27, 2024. Full clinical study reports, patient-level pharmacovigilance data, and complete hyperphosphatemia rates were not publicly accessible in the abstract.
Cross-Trial Comparison Limits: Direct comparison of response rates and duration of response across ReFocus, FIGHT-202, and TAS-120-101 is non-randomized, unstratified, and methodologically invalid for establishing comparative efficacy or safety superiority.
Diagnostic Panel Fluidity: Companion diagnostic assessments are based on published PMA supplement documentation for FoundationOne CDx P170019/S013 (Pemazyre, April 17, 2020) and P170019/S021 (Truseltiq, May 28, 2021). FDA may approve concurrent PMA supplements or clear alternative diagnostic tests upon drug approval. Historical IFU Table 1 snapshots can lag the live CompanionDiagnostics listing.
Payer Policy Snapshots: Documented prior authorization policies from FEP Blue (5.21.144; April 2026), NHPRI / Evolent (UM-ONC_1398; July 2024), and UnitedHealthcare (2024 P 1399-3; February 2025) represent documented public policies as of their stated effective dates and do not constitute an exhaustive survey of all U.S. commercial, Medicare Advantage, or Medicaid health plans.
No Individual Clinical or Financial Advice: This analysis is published exclusively for biopharma industry professionals, health system formulary managers, and market access researchers. It does not provide medical guidance, dosing instructions, or investment advice.

Sources

1. Elevar Therapeutics, Elevar Therapeutics Announces FDA Acceptance for Priority Review of New Drug Application for Lirafugratinib as Second-line Cholangiocarcinoma Treatment, press release, March 30, 2026; Priority Review grant and PDUFA target action date of September 27, 2026.

2. U.S. Food and Drug Administration / National Library of Medicine, PEMAZYRE (pemigatinib) Prescribing Information, DailyMed SPL setid 9e1f2222-1d89-4e63-989c-ccebe2ab1eb4, effective_time 20260609, version 17; NDA 213736, Incyte Corporation; Section 1.1 accelerated approval, Section 2.1 companion diagnostic requirement, and Section 5 warnings.

3. U.S. Food and Drug Administration / National Library of Medicine, LYTGOBI (futibatinib) Prescribing Information, DailyMed SPL setid 0b1332a1-0581-4707-9bf6-1eccfa39bef4, effective_time 20251027, version 8; NDA 214801, Taiho Oncology, Inc.; Section 1 intrahepatic accelerated approval, Section 2.1 absence of FDA-approved test, and Section 5 warnings.

4. U.S. Food and Drug Administration, WITHDRAWN: FDA Grants Accelerated Approval to Infigratinib for Metastatic Cholangiocarcinoma, May 28, 2021 accelerated approval of NDA 214622 (QED Therapeutics) with concurrent FoundationOne CDx approval, and May 16, 2024 update announcing final withdrawal; CBGJ398X2204 (NCT02150967) ORR 23 percent (95% CI: 16–32), median duration of response 5 months (95% CI: 3.7–9.3), n=108.

5. ClinicalTrials.gov, NCT04526106: REFOCUS: A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, actual enrollment 490, sponsor Elevar Therapeutics, completed status, last updated February 27, 2026.

6. A. Hollebecque et al., Efficacy and Safety of Lirafugratinib in FGFRi-Naive Cholangiocarcinoma (CCA) Patients Harboring FGFR2 Fusions/Rearrangements (FGFR2 f/r), Journal of Clinical Oncology, 2026; 44(suppl 2): abstract 476, published online January 12, 2026; IRC n=114 ORR 46.5% (95% CI: 37.1–56.1%), data cutoff September 27, 2024.

7. Blue Cross Blue Shield Association / Federal Employee Program, FEP Blue Pharmacy Policy 5.21.144: Pemazyre (pemigatinib), last reviewed March 6, 2026, effective April 1, 2026; requiring FDA-approved test, ophthalmologic exams, and serum phosphate monitoring; listing Truseltiq under related policies.

8. Neighborhood Health Plan of Rhode Island / Evolent Health, Pharmacy Medical Policy UM-ONC_1398: Pemazyre (pemigatinib), approved July 10, 2024, effective July 26, 2024; Section II exclusion of prior FGFR2 inhibitor therapy.

9. UnitedHealthcare, Pharmacy Clinical Pharmacy Programs 2024 P 1399-3: Lytgobi (futibatinib) Prior Authorization/Notification, approved November 2024, effective February 15, 2025; authorizing intrahepatic and extrahepatic cholangiocarcinoma based on NCCN compendia.

10. U.S. Food and Drug Administration, Drugs@FDA Application Directory & API, API last updated September 2, 2026; NDA 213736 (Pemazyre) and NDA 214801 (Lytgobi) records present. A parallel search for the ingredient name lirafugratinib returns no matches; there is no posted application whose brand or generic name is lirafugratinib or RLY-4008.

11. Centers for Medicare & Medicaid Services, Medicaid National Average Drug Acquisition Cost (NADAC) 2026, public datastore query for ndc_description matching PEMAZYRE, PEMIGATINIB, LYTGOBI, and FUTIBATINIB returning 0 records on September 4, 2026.

12. ClinicalTrials.gov, NCT07359820: A Study of Lirafugratinib in Non-CCA Solid Tumors With FGFR2 Fusion or Rearrangement (ReFocus202), estimated enrollment 30, study start June 4, 2026, status recruiting, last updated September 3, 2026; cholangiocarcinoma excluded.

13. U.S. Food and Drug Administration / Center for Devices and Radiological Health, FoundationOne CDx PMA P170019/S013, approved April 17, 2020, for FGFR2 fusions and select rearrangements in cholangiocarcinoma for pemigatinib (Pemazyre); and P170019/S021, approved May 28, 2021, for FGFR2 fusions/rearrangements in cholangiocarcinoma for infigratinib (Truseltiq). P170019/S016 (June 16, 2020) is the tumor-mutational-burden/pembrolizumab supplement, not Pemazyre.

14. U.S. Food and Drug Administration, Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations, NDA 213736 (Pemazyre) products 001, 002, 003 (TE blank, ODE expirations through 2027 and 2029) and NDA 214801 (Lytgobi) product 001 (4 mg, TE blank, NCE expiration 2027) and product 002 (16 mg, Discontinued).

15. U.S. Food and Drug Administration, Helsinn Healthcare SA; Withdrawal of Approval of New Drug Application for TRUSELTIQ (Infigratinib Phosphate) Capsules, 25 Milligrams and 100 Milligrams, 89 FR 42887, May 16, 2024, Docket FDA-2024-N-2178; withdrawal under 21 CFR 314.150(d) at Helsinn's request.

16. ClinicalTrials.gov, NCT03773302: The PROOF Trial, Phase 3 infigratinib versus gemcitabine plus cisplatin in first-line FGFR2-altered cholangiocarcinoma; lead sponsor QED Therapeutics, a BridgeBio company; status terminated.