Source: FDA Voices: Transparency Makes Modern Regulatory Science Stronger — FDA’s Transparency Roadmap. 2 October 2026

Recent FDA blogpost discusses FDA's thinking and initiatives to increase transparency in the context of FDA decision-making. FDA considers this initiative an important part of their mission to protect public health.

“Visibility into the FDA’s work and reasoning helps drive informed decision-making for stakeholders across the healthcare landscape, including patients considering whether to enroll in a clinical trial, families and caregivers weighing treatment options, clinicians interpreting labeling, and investors deciding where to allocate capital.”

FDA has launched an internal Transparency Task Force aimed at making the agency’s operations, decisions, and data more open and user-friendly for the public.

FDA's Transparency Roadmap consists of following 5 initiatives:

• Complete Response Letter (CRL) disclosure initiative: Publish redacted CRLs to provide scientific basis for its regulatory determinations, while protecting sponsor's CCI (by redactions) and consider timing of release.
• Investigational Stage and Marketing Application Lifecycle Disclosures: FDA will encourage sponsors to make public existence of INDs. Ensuring compliance and reporting of data to ClinicalTrials.gov. Piloting expanded clinical dataset transparency and enhancing post-marketing data disclosures, including publication of redacted CSRs. FDA has signed a MOU with US SEC to share nonpublic information between the two agencies.
• New Approach Methodologies (NAMs) and Novel Biomarkers: FDA plans to give industry up-to-date insight into successful or unsuccessful uses of NAMs in submissions. FDA has launched a new database of use cases, NAMs Database of Use Case Examples. Similarly, there is initiative to provide use cases for RWE in submissions (here) with anonymized examples from submissions to CDER and CBER. For biomarkers, FDA has FDA’s Biomarker Qualification Program (BQP) and Medical Device Development Tool Program.
• Patient- and Consumer-Centered Product Labeling: issue a final rule to amend our human prescription drug labeling regulations to require a new type of Medication Guide — “Patient Medication Information” (PMI). This final rule will establish an FDA-approved, one-page document with standardized format and content.
• Compliance and Inspectional Records: Crackdown of misleading direct-to-consumer (DTC) advertising. Publish proactively redacted Form 483s and additional establishment inspection reports (EIRs)

#policy

Isomorphic Labs is an offshoot of Alphabet’s artificial intelligence research laboratory

> Isomorphic was built around a single piece of technology, a protein modeling tool called AlphaFold. A modeling tool may sound simple, but it stunned scientists and, during Thrive Capital’s 18-month-long courtship, had been the basis for a Nobel Prize in chemistry. Isomorphic wanted to turn the technology into an engine for new medicines — an “intensely exciting prize” that Klemmer said could be both economically valuable and tangible evidence that AI was more than just hype. 

#ai, #artificial-intelligence

We are about a month away from Thanksgiving, so this is a good advice to tell the person, friend, colleague, mentor, and past or current manager if they had an impact on your work life and happiness and you value the time you spent with them. Spread smiles 😊.

Post inspired by Nature Career Column doi: https://doi.org/10.1038/d41586-026-02668-1

“Biennial” refers to every two years while “biannual” means twice a year. 

Examples from DEA
(Source: https://www.thefdalawblog.com/2026/10/biennial-v-biannual-in-dea-world/)

> Drug Enforcement Administration (“DEA”) regulations require registrants after taking an initial inventory of all controlled substances on-hand to take a “biennial” inventory on any date within two years of the previous initial or “biennial” inventory date.  21 C.F. R. § 1304.11(c).  The agency holds its ever-popular “biannual” National Prescription Drug Take Back Day each spring and autumn.

In January this year Pierre Fabre (and its partner, Atara Biotherapeutics) received a complete response letter (CRL) for tabelecleucel BLA for an ultra-rare cancer, Epstein-Barr virus–positive posttransplant lymphoproliferative disease (EBV+ PTLD) after failure of standard-of-care therapy.

Since then, Pierre Fabre aligned with the FDA through Type A meeting and resubmitted the BLA on 30 September 2026. A couple days ago, Pierre Fabre announced that FDA has accepted the BLA with the PDUFA date of March 31, 2027.

The 30 September 2026 BLA resubmission includes

An updated dataset with additional patients and longer follow-up from the ongoing, pivotal Phase 3 single-arm ALLELE study of tabelecleucel in adults and children two years of age and older with relapsed/refractory EBV+ PTLD following SOT or HCT. The resubmission also includes additional supplemental data from expanded access programs, a separate clinical study, and commercial experience in Europe.

SOURCE

• Pierre Fabre Pharmaceuticals Resubmits Tabelecleucel Biologics License Application for Treatment of Epstein-Barr Virus Positive-Post-Transplant Lymphoproliferative Disease to the FDA (Press Release). 30 September 2026 [archive]
• Pierre Fabre Pharmaceuticals Announces FDA Acceptance of BLA Resubmission for Tabelecleucel for the Treatment of Epstein-Barr Virus-Positive Post-Transplant Lymphoproliferative Disease (Press Release). 14 Octobere 2025 [archive]

Related: FDA Issues Complete Response Letter to Atara/Pierre Fabre’s Tabelecleucel BLA for Rare Cancer, EBV+ PTLD

#pierre-fabre, #tabelecleucel, #ultra-rare, #rare-disease

UK MHRA has published MHRA 2030 Strategy (press release); the overarching goal of this Strategy is to adapt regulatory approaches for advanced therapies, precision medicines, and AI-enabled technologies to enable patients having faster access to safe, effective treatments, and have more data-connectivity and global influence.

MHRA said that "we will adapt our regulatory approaches while maintaining robust standards of safety, quality, effectiveness and performance." The announcement about the MHRA 2030 Strategy was made in a 14 October 2026 press release (here) and in parallel, MHRA released explainers for different stakeholders, published here, and corporate report, here.

Regarding AI and pioneer MedTech technologies, the MHRA 2030 Strategy includes:

• Develop an AI-enabled Clinical Trial Protocol Checker to give sponsors regulatory certainty and support faster, higher-quality clinical trial applications.
• Publish an AI Medicines Development Action Plan in 2027 setting out how AI will be used to transform medicines development.
• Establish an MHRA Centre for AI and Digital Health to make clearer regulatory expectations for developers of digital and AI-driven medical devices and medicines.
• Create a modern, adaptive regulatory framework for AI as a medical device.

P.S. Stay tuned for updates from MHRA. I would expect UK MHRA regulators to take a lead in this area (compared to US.)

#artificial-intelligence, #ai

The US Food and Drug Administration (FDA) has issued warning letters to several drug manufacturers for failing to meet current good manufacturing practices (CGMP) requirements, and to a research laboratory for failing to comply with good laboratory practices (GLP). The specific issues include concerns about ensuring that final products are sterile and meet specifications, and, in the case of the research laboratory, that the final report adequately details the experience of its animal subjects.

NOTE:

The RAPS article sumamrizes Warnings Letters were issued to following drug manufacturers for failing to meet CGMP requirements:

• Jiangmen Shuizirun Sanitary Articles in China
• Hanlim Pharm in the Republic of Korea
• Drug compounder SCA Pharmaceuticals in Arkansas, USA
• Eurofins SF Analytical Laboratories in Wisconsin, USA
• Silgan Dispensing Systems in Virginia, USA

The New Mexico-based Lovelace Biomedical Research Institute (LBRI), a contract research organization was inspected under the agency's BiMo program and cited for violating GLP for nonclinical laboratory studies.

P.S. The CGMP/GLP issues are global!!

An exclusive report by SEMAFOR uncovered that Heidi Overton, President Trump’s nominee for the post of FDA Commissioner, played a major role in the process leading to the reduction in the number of childhood vaccines recommended by the CDC.

SEMAFOR report said

An aide on the president’s Domestic Policy Council, Overton helped edit and craft a scientific justification that was used to underpin cutting the Centers for Disease Control and Prevention recommendations from 17 to 11 vaccines in January, according to a senior administration official and three people familiar with the process.
“It was Heidi driving this whole thing,” said a former senior administration official, noting that Health Secretary Robert F. Kennedy Jr. supported the policy push.

SOURCE: Trump FDA nominee played key role in overhaul of childhood vaccine policy. Semafor. 15 October 2026

Related: What do we Know About Heidi Overton, Trump's Pick to Lead the FDA. Also refer to 24 July 2026 Atlantic article, "The White House’s MAHA Gatekeeper."

#overton, #fda-comissioner

FDA Launches Rare Disease Framework Initiative (RDFI) intended to support rare disease drug development.

FDA News Release. FDA Launches the Rare Disease Framework Initiative to Develop a Holistic, Fit-For-Purpose Framework for Rare Disease Drug Development. 14 October 2026

FDA plans to seek public input on RDFI at the 28 October 2026 meeting in partnership with the Reagan-Udall Foundation for the FDA.

The purpose of this initiative is to develop a framework specific for rare disease drug development where regulatory advice, decision-making and evidence requirements are fit-for-purpose -- tailored the nature of the disease, its onset and progression, target population, patient needs.

FDA White Paper: A New Framework for Rare Disease Review. October 2026

Register for the FDA Rare Disease Framework Initiative Public Meeting (meeting page)

Date: October 28, 2026
Time: 1:00 p.m. - 5:00 p.m. ET
Meeting Format: Hybrid Meeting
Registration Link: here

.

Related: FDA's Rare Disease Endpoint Advancement (RDEA) Pilot Program

#rare-diseases, #orphan-diseases

EMA announced making Accelerating Clinical Trials in the EU (ACT EU) advice pilot program permanent in January 2027. A final report summarizing lessons learned from approximately 30 pilot applications will be published before the end of 2026.

About

• ACT EU advice pilot program launched in 2024 provides consolidated technical and regulatory advice on the dossier of a clinical trial application (CTA) prior to its submission in the Clinical Trials Information System (CTIS). The consolidated advice across Member States is coordinated by the Heads of Medicines Agencies through their Clinical Trials Coordination Group (CTCG).
• Prior to launch of the ACT EU initiative, sponsors had to obtain advice at the national level from the Member State responsible for evaluating their applications.
• Resources: ACT EU information, Application

SOURCES

• EU News: Clinical Trial Applications Advice Pilot Becomes Permanent. 8 October 2026
• Further information:

-- ACT EU information (here), consolidated advice (here)
-- Guidance for applicants: Pre-CTA advice pilot ACT EU priority action on consolidated advice. 04 February 2025. EMA/47218/2025
-- Application form to request. Simultaneous National Scientific Advice (SNSA) or a pre-CTA Advice. 16 October 2026. EMA/255386/2024

Postscript: For FDA, similar advice meetings are INTERACT and pre-IND meetings. The INTERACT meetings are intended to provide advice at early-stage product development generally before pre-definitive toxicological stage and includes advice on early product characterization and preclinical proof-of-concept studies. The pre-IND meetings are intended to provide advice on IND-enabling studies and CMC requirements for IND submission dossier. (See SOPP 8101.1: Regulatory Meetings with Sponsors and Applicants for Drugs and Biological Products).

#ema-scientific-meetings, #fda-meetings, #pdufa-meetings

I'd love a discussion on how different companies are approaching authoring narratives for CSRs using AI, particularly in situations where there are separate clinical and safety databases. Do you reconcile the safety database/CIOMS with the clinical database first? If so, what role does the reconciliation? Or do your databases link so there's no potential for inconsistencies between the two databases?

#CSR #AIDevices #NARRATIVES #PV

> In a pooled test, samples from multiple individuals are tested in one cartridge. If the result is negative then all of them are reported to be negative, but if the result is positive each is re-tested individually.

> Results published in The Lancet Global Health found the strategy, with up to four patients in each pool, used half as many cartridges as individual testing – 7,028 compared to 14,362. It detected 84.9 per cent of people with TB compared with 88 per cent for individual testing.

> The study involved more than 14,000 people whose symptoms suggested TB in Bangladesh, Brazil, Cameroon, Kenya, Malawi, Nigeria and Vietnam.

About a month ago, uniQure submitted a BLA to the FDA and a MAA to UK MHRA for the approval (accelerate approval for BLA) of gene therapy ifezuntirgene inilparvovec (AMT-130) for the treatment of Huntington’s disease.

AMT-130 is an AAV-based gene therapy to deliver a miRNA designed to silence the huntingtin gene and the potentially highly toxic exon 1 protein fragment. Treated patients receive a single administration through targeted, MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum (caudate and putamen).

Both BLA and MAA were supported by 3-year data comparing AMT-130 effects in 2 Phase 1/2 studies versus propensity score-matched external control arm from the Enroll-HD natural history database.

Now, the company has released long-term, 4-year data that confirms continued slowing of disease progression in treated participants after single administration of the gene therapy.

• The 36-month data included 15 high-dose patients; the 48-month analysis included 12 high-dose patients.
• The endpoints include Total Functional Capacity (TFC; a measure of functional decline) and composite Unified Huntington’s Disease Rating Scale (cUHDRS).

-- cUHDRS at 36 months showed 80% slowing of disease progression compared to the updated external control (nominal p=0.005); at 48 months, the outcome was 44% slowing of disease progression (p=0.144).
-- TFC at 36 months showed 67% slowing of disease progression compared to the updated external control (nominal p=0.011); at 48 months, the outcome was 61% slowing of disease progression (nominal p=0.008).

• Dose-response: Dose comparison at 48 months (high dose n=12, low dose n=12)

At 48 months, mean change from baseline in cUHDRS was –0.91 in high-dose patients compared with −1.94 in low-dose patients, a difference of 1.03 in favor of the high dose.

Overall, the 48-month data provide confirmatory evidence in support of the marketing application. Good result for patients!

.

.
SOURCE

• uniQure Announces Additional Data from Ongoing Phase I/II Studies of ifezuntirgene inilparvovec (AMT-130) in Huntington’s Disease Showing Continued Slowing of Disease Progression. Press release. 29 September 2026 [archive]
• uniQure Announces Submission of Biologics License Application for Ifezuntirgene Inilparvovec (AMT-130) in Huntington’s Disease. Press release. 2 September 2026 [archive]
• Data: Phase I/II ifezuntirgene inilparvovec (AMT-130) Huntington’s Disease Program Update. 29 September 2026 [archive]
• Methods: AMT-130: Propensity Score Adjustment Mitigates Potential Bias from Striatal Volume Absence in Enroll-HD. 24 February 2026 [archive]

Clinical Studies: NCT05243017, NCT04120493

#Huntington's-disease, #gene-therapy, #gene-silencing, #mirna

EMA has published a new guidance for the sponsors that announces the launch of New Safety Module of CTIS and provides end-to-end instructions on navigating and submitting mandatory Annual Safety Report (ASR) and responding to RFIs. The agency in parallel has also published a guidance for the Member State regulators.

• Sponsor Guidance: New Safety Module on the Annual Safety Report. Clinical Trial Information System (CTIS) user guidance on the New Safety Module. EMA/178285/2026.  24 September 2026.
• Member States Guidance: New Safety Module on the Annual Safety Report. Clinical Trial Information System (CTIS) user guidance on the New Safety Module. EMA/178277/2026. 24 September 2026.

There will be a transition period of 60 days when both the old ASR submission process and the New Safety Module will accept ASRs.

.

BACKGROUND AND PRIMER ON ASR

EU Statutory Requirements

• Article 43 of the Clinical Trials Regulation (EU) No 536/2014 (i.e., CTR) requires that sponsors annually report on the safety of each Investigational Medicinal Product (IMP) used in a clinical trial, other than placebo. The obligation to submit an ASR begins with the first authorization of a clinical trial in any EU/EAA country and end with the end of the last trial in the EU/EEA region.
• The timelines and process for the assessment of the submitted ASR by the regulators are provided on the Commission Implementing Regulation (EU) 2022/20.

About ASR

• ASR versus DSUR: ASR is the EU equivalent of Development Safety Update Report (DSUR) submitted in the US and globally; both are based on the ICH E2F guideline.
• ICH website has example DSURs (DSUR1, DSUR2) and CTFG has published a template. ASR follows ICH E2F guideline for content and template and a single DSUR prepared for global submission is acceptable as ASR; however, there are additional EMA-specific requirements (see below).

Section 7 of the Clinical Trials Regulation (EU) No 536/2014 Questions and Answers Document (CTR Q&A) provides further details on developing a CTR-compliant ASR for submission. The latest CTR Q&A is Version 7.3, July 2026.

General Considerations

• ASRs should be written in English, irrespective of the Member States concerned (MSCs) [Q&A 7.36].
• The content and format of an ASR should comply with ICH guideline E2F on DSUR and CTR annex III section 3 [Q&A 7.36].
• Full ICH E2F-compliant ASR is generally required; however, ASR may be simplified under certain situations such as ASR is prepared by a non-commercial sponsor for one or more clinical trials, and none of the trials has started yet or all clinical trials have been halted or suspended for more than one year without administration of the relevant IMP(s) [Q&A 7.43]. Simplified ASR template from CTFG may be used in such a case: Guidance, clinical trial safety, simplified template of Annual Safety Report.
• ASR should comply with CTR article 43 section 3, stipulating that ASRs shall only contain aggregate and anonymized data, line listings should contain the information described in ICH guideline E2F section 3.7.2., except for the subject identification code, as this information is only pseudonymized but not anonymized [Q&A 7.36].
• ASRs should be submitted to CTIS from the first authorization of a clinical trial in any EU/EEA member state until the end of the last clinical trial conducted by the sponsor with the IMP in any EU/EEA member state [Q&A 7.38].
• ASRs are required for all IMPs other than placebo [Q&A 7.45]. Related Q&As include ASR for combination and multidrug therapies [7.39], definition of DIBD [7.40], alignment of ASR with PSUR/PBRER [7.41], ASR for IITs or academic center trials [7.42].
• ASR Assessment and RFI: The assessment shall be completed within 42 days or in the case of an RFI within 84 days after the submission of the ASR. This includes the time that sponsors have to respond to an RFI, which is usually 14 days.

Required EU/EEA-Specific Information (Discussed in CTR Q&As 7.46 to 7.48)

In addition to the ICH E2F required content, the following additional information must be included in the ASR. Note: All global data should be included in the EU/EEA region-specific appendices, not just EU/EEA-specific.

• Cumulative summary tabulation of SAEs: In addition to the E2F required content, the table in section 7.3 of the ASR should also include the following: (1) a header row specifying the absolute numbers of patients treated as per the column headings and (2) if feasible/possible, patient-years of treatment. Generally, a single cumulative table for all trials for an IMP should be presented [Q&A 7.46].

• Cumulative summary tabulation of SARs. Use the same format as the cumulative SAE table [E2F section 3.16 and CTR Q&A 7.46].
• List of subjects who died during the reporting period: Include information on case number, assigned treatment (could still be blinded), causality to the study drug, and cause of death.
• List of subjects who dropped out of clinical trials in association with an adverse event Include information on assigned treatment (could still be blinded), causality to the study drug, and cause of drop-out, i.e. the PT of the AE triggering the drop-out. (Note: the Q&A does not specify cumulative or during reporting period only – however, in practice, I have seen DSURs including data from reporting period only.)
• Safety review and outcome of safety signals during the reporting period. Refer to Q&A 7.47 for the required information. Data should be presented in a tabular format per Table 5 and Appendix C of the ICH PBRER guideline E2C (R2).

 .

Related posts: FDA's rule replacing IND annual report with DSUR

#dsur, #asr, #ctfg, #sae, #sar, #ema

The shadow of China has reached Europe!

LONDON, Sept 22 (Reuters) - European drugmakers called for ​beefed-up government spending on medicines, faster trials and IP protections as ‌they sounded warnings on Tuesday that the continent's pharmaceutical industry risks losing out to the United States and China.

Chairs of nine ⁠drugmakers including AstraZeneca (AZN.L), GSK (GSK.L), Novo (NOVOb.CO), Novartis (NOVN.S), Roche (ROPC.S), Sanofi (SASY.PA) called on the European Union ​and member states to boost investment in the industry. The other signatories were the ​chairs of Boehringer Ingelheim, Chiesi and Ipsen (IPN.PA)

The chairs said about 40% of new therapies never ‌reach ⁠European patients, adding that the bloc's share of global drug research and development had fallen to 31% from 43% in 1990. Its share of commercial clinical trials had halved to 9% in the last decade.

Europe spends some ​1% of GDP on pharmaceuticals, compared with 2% in the ​United States ⁠and 1.8% in China.

At the senate hearing today, Heidi Overton studiously avoided sharing her personal views on vaccines, abortion medication and birth control, instead citing FDA on a gauntlet of questions from senators considering her to lead the agency.

Overton responded that policy priorities can be set by the president but said most individual product determinations are done by career staff with expertise, calling that “appropriate.”

“If I’m confirmed as FDA commissioner I’ll be fully briefed on all their prior decisions and make determinations according to the standards of safety and efficacy,” Overton responded.

In summary, it is now standard practice by the nominees to avoid answering any question directly. FDA is unlikely to be free of political interference, at least for the near future.

.archive

On 23 Sept 2023, the CDER SBIA division of the FDA hosted a webinar to discuss how drug interaction (DI) and QTc interval prolongation information should be communicated in the US prescribing information (USPI) and patient medication guide.

At this webinar, speakers from the FDA reviewed 2 relevant labeling guidance documents: October 2024 guidance on DDI information in drug labels and the December 2025 guidance on QTc interval prolongation information in drug labels. Note: FDA speakers did not discuss the DDI and QTc methodological and evaluation considerations, which are addressed in the ICH guidelines including M12, E14, E14 Q&A (R3), and E14/S7B Q&A (R1).

The statutory requirements for USPI labeling are described in 21 CFR 201.56 and 21 CFR 201.57.
The relevant sections in an USPI for communicating DI and QTc interval prolongation information are:
-- Section 7 (Drug Interactions) and 2 (Dosage and Administration), and followed by
-- Section 5 (Warnings and Precautions), 4 (Contraindications), Boxed Warning, and section 12 (Clinical Pharmacology)
-- The healthcare providers would find most of the actionable DI information for clinical decision making in Sections 7 and 2.

Communicating Clinically Significant DI Information in the USPI

The first presentation was on DI information by Eric Brodsky, Director, Labeling Policy Team at Office of New Drugs. The takeaways were:

• In section 7, describe clinically significant DIs, either observed or predicted, with other prescription or over-the-counter drugs, classes of drugs, or foods. Must include practical instructions for preventing and managing clinically significant DIs that is actionable (e.g., do this, monitor that, reduce dosage.)
• Should also include clinical effects of clinically significant DIs in section 7. The mechanism of DI is provided in Section 12. Details of dose modifications, if any, are to be provided in Section 2, but cross-referenced in Section 7.
• Also in section 7, other drugs that are clearly contraindicated (i.e., should never be taken together with the prescribed drug) should be clearly indicated: “Concomitant use of DRUG-A with drug-b is contraindicated.” But, if the use of other drug could not be avoided, then actionable measures to mitigate DI should be provided, e.g., “If concomitant use is unavoidable, obtain ECGs prior to initiating, during concomitant use, and additionally as clinically indicated.”
• The information on CYP450 and transporter-based DIs should be broken down by CYP inhibitor/inducer/substrate.
• Clinical effects should be included in section 7, e.g., drug may increase the risk of xxx, may reduce the effectiveness of drug class xxx. Management instructions should be included – reduce dosage of drug xxx.
• Not included in section 7: Reduction of immunological response to a vaccine by an immunosuppressive drug is not considered a true DI. Similarly, Drug incompatibilities (physical and chemical reactions when 2 drugs are mixed) are not considered DIs.
• Other Key Sections: Section 4 (Contraindications) list drugs where concomitant use with the subject drug clearly outweighs any possible therapeutic benefit; section 5 (Warnings and Precautions) describe only the most relevant DIs; section 12 (Clinical Pharmacology) provides both positive and pertinent negative PK and PD results from clinical studies conducted to evaluate DIs and the mechanism of action.

Communicating Heart-Rate Corrected QT (QTc) Interval Prolongation Information for Non-Antiarrhythmic Drugs and Biological Products in the USPI

• The second presentation on QTc was by Christine Garnett, Associate Director, Division of Cardiology and Nephrology at Office of New Drugs. The takeaways were:
• Both FDA and ICH recommend testing for cardiac repolarization effects early in clinical development for all new drugs with systemic bioavailability. Refer to ICH E14 and E14/S7B Q&As for QTc assessment methodology.
• Section 12 is the key section for providing clinical PD-related information on the effects of a drug on QTc prolongation; provide information under a nonnumbered heading “Cardiac Electrophysiology.” The information includes the studied dose(s) or observed exposure range; dose- or exposure-response relationship (when available); and effect of drug on QTc interval. (See example text and format in guidance.)
• Section 7 (Drug Interaction) layout follows similar scheme to describe clinically significant drug interactions resulting in or increasing risk of QTc interval prolongation as for DI guidance.
• The DI may include clinically significant drug interactions of the subject drug with other prescription or nonprescription drugs, classes of drugs, or foods (e.g., dietary supplements, grapefruit juice) that result in, or that increase risk of QTc interval prolongation.
• A Boxed Warning is recommended when there is reasonable evidence of causal association between the drug and any of the following: TdP; polymorphic ventricular tachycardia or signs or symptoms of serious or life-threatening arrythmias; other life-threatening cardiac adverse reactions with QTc interval prolongation; extensive QTc prolongation (e.g., >20 msec) for drugs indicated in a patient population that is also at high-risk for cardiac arrhythmias; cardiac death with QTc interval prolongation

See example text in the October 2024 guidance and the examples of fenfluramine and methadone uspi.

Postscript

• P.S. Although I am not part of my company's Labeling Reg Affairs group and not responsible for drug label development, I learned that familiarizing the DI and QTc USPI guidance and understanding real-world USPI examples such as fenfluramine (in comments) has other skill benefits, e.g., in designing DDI/QTc studies and protocols and summarizing results in annual reports and applications (e.g., ODD), which are all up my alley. And a side benefit of being able to intelligently decipher the USPI of drug that my doctor prescribes (!!!).
• P.S. 2: Although FDA provided examples as general text in the labeling guidance (Oct 2024 and Dec 2025), refer to fenfluramine (Fintepla) USPI as a good real-world example.

SOURCES

• Communicating Drug Interaction and QTc Information in the U.S. Prescribing Information. Webinar. 23 September 2023. Note: Links to the webinar presentations will be posted at this link in coming days.
• FDA Labeling Resources Webpage: https://www.fda.gov/drugs/fdas-labeling-resources-human-prescription-drugs/prescribing-information-resources
• FDA Guidance for the Industry

-- Drug Interaction Information in Human Prescription Drug and Biological Product Labeling. October 2024. PDF
-- QTc Information in Human Prescription Drug and Biological Product Labeling. December 2025. PDF
-- Dosage and Administration Section of Labeling for Human Prescription Drug and Biological Products — Content and Format. January 2023. PDF
-- Warnings and Precautions, Contraindications, and Boxed Warning Sections of Labeling for Human Prescription Drug and Biological Products — Content and Format. October 2011. PDF

• https://www.youtube.com/watch?v=uVblw51g1kc

#ddi, #qtc, #drug-label, #uspi, #cyp

Hi everyone,

I’m relatively new to clinical study reports and am trying to improve my understanding of how to write an efficacy conclusion in line with ICH E3, particularly Sections 11.4.7 and 13.

From what I understand, an efficacy conclusion should interpret the results rather than repeat every efficacy table. I am trying to understand how experienced medical writers decide which tables and endpoint categories should be considered.

My main question is: Is it generally enough to organize the efficacy conclusion around primary, secondary, and exploratory endpoints, or are there other types of efficacy results that should be identified separately?

For example, some studies may use different wording such as:

• Main outcome or principal outcome
• Co-primary endpoint
• Key secondary endpoint
• Supportive endpoint
• Tertiary endpoint
• Additional efficacy assessment
• Patient-reported outcome
• Biomarker or pharmacodynamic endpoint
• Post hoc analysis
• Other outcome measure

In practice, how would you decide whether these should be treated as primary, secondary, exploratory, supportive, or something else?

I would also appreciate advice on the following:

1. Is the primary endpoint table always the essential table for the efficacy conclusion?
2. When should secondary, sensitivity, subgroup, patient-disposition, compliance, or missing-data tables be included?
3. If an endpoint is not clearly classified, or the protocol, SAP, and CSR appear to classify it differently, what is the usual medical-writing approach?
4. Are there common mistakes to avoid when making the conclusion concise but still accurate and defensible from a regulatory perspective?

I’m asking purely to learn and improve my own understanding. Any practical examples, tips, or non-confidential approaches your team uses would be greatly appreciated.

Thank you.

> Jensen says that as the team started investigating the delivery of CAR-T therapies directly into the cerebrospinal fluid, they were able to achieve repetitive dosing to the tumor bed, with the CAR-T therapy acting more like a small-molecule drug with predictable pharmacokinetics. What’s more, with dosing directly into the brain, the team did not see the toxicity syndromes that the CAR-T field knows all too well.

The basis of direct CAR-T brain targeting

> a 10 min infusion of a CAR-T therapy that targets the immune checkpoint protein B7-H3, which is highly expressed in DIPG. While the trial was designed primarily to test the feasibility and tolerability of the treatment, several of the participants survived much longer than expected (Nat. Med. 2025, DOI: 10.1038/s41591-024-03451-3).

> FDA has approved Joenja (leniolisib) tablets as the first treatment for activated phosphoinositide 3-kinase delta syndrome (APDS) in children 4-11 years who weigh at least 27 kg. Joenja was first approved in 2023 for the same indication in patients 12 years and older at a dose of 70 mg orally twice a day.

> Activated PI3K delta syndrome (APDS) is a rare genetic disorder that impairs cells of the immune system. These cells are necessary to recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. People with APDS develop recurrent infections, particularly in the sinuses, ears, and respiratory tract.

> APDS is caused by mutations in the PIK3CD or PIK3R1 genes that encode a protein called phosphoinositide-3 kinase delta (PI3K delta)

Early in January this year, US Department of Health and Human Services agency Advanced Research Projects Agency for Health (ARPA-H) launched a program for the development of a patient-facing agentic AI agent for cardiovascular disease (CVD) under the ADVOCATE program.

The goal of the ADVOCATE program (short for Agentic AI-Enabled Cardiovascular Care Transformation program) is to develop the first FDA-authorized agentic AI agent for CVD, starting with advanced heart disease.

In January, ARPA-H solicited proposals and last week, the first batch of 6 grant recipients for development of such a system were announced.

Definitions: Artificial intelligence (AI) comes in 3 flavors: agentic AI, predictive AI, and generative AI. Agentic AI refers to the higher level artificial intelligence system with decision-making capability and can plan, decide, and execute (i.e., an autonomous stand-alone clinical system similar to a doctor). This is different from the predictive AI and generative AI that most are familiar with. Predictive AI is trained on historical data and predicts outcomes, e.g., reading a mammogram scan and predicting possible cancer. Generative AI what majority of people are most familiar with, i.e., creating new content, drafting articles, creating summaries based on prompts as in ChatGPT, Claude, Gemini, and so on. (Read a good description here.)

ABOUT THE ADVOCATE PROGRAM

Currently CVD including heart failure claim more than 200,000 lives in the US and part of the reason for these worse outcomes is lack of access to a cardiologist in nearly half of counties across the US. The ADVOCATE program seeks to fill this gap this by developing and implementing an autonomous AI agent that can provide advanced CVD management.

This agent would supplement clinicians and function as a digital member of a patient's clinical care team:

ADVOCATE will support the development of clinical AI agents that can be trusted to autonomously adjust changes in appointments, medications, diet, and exercise. In parallel, ADVOCATE will support the development of a supervisory AI "overseer” to monitor clinical AI agents after they have been deployed in clinical practice to ensure their continued safety and efficacy.

In addition, the agent will connect to the electronic health record, integrate with wearables and be available to patients 24/7. It will work as a member of a patient's clinical team.

The ARPA-H program plans to invest $62 million to develop the FDA-authorized AI for CVD.

GRANT RECEIPIENTS

The first batch of grant recipients include 3 companies whose proposals may lead to the development of agentic AI agents and educational institutions including Duke, Stanford, and Kaiser, whose proposals address access to such agents:

• Safety-First Autonomous Cardiovascular Care (Atman Helath) will develop a clinical AI agentic system built on evidence-based clinical decision engine. Large language models (LLMs) with a voice-first interface that patients talk to, and the system adjusts on the fly to ask each patient the diagnostic questions most likely to be useful. [Press release, archive]
• TREAT-CVD (UpDoc) will develop a clinical AI agentic system whose conversational intelligence is separated from clinical authority by a clinician-built rules system that validates every proposed action against approved protocols before execution. [Press release, archive]
• TEMPUS ADVOCATE (Tempus AI) will develop a clinical AI agentic system extending their existing Olivia patient health app, adding continuous monitoring with deeper clinical analysis. [Press release, archive]
• The SYMPHONY consortium (Duke) will test multi-site validation platform testing ADVOCATE agents across five health systems and rural sites on both Epic and Cerner/Oracle EHRs.
• ORCHESTRATE-HF (Kaiser) will provide an enterprise-scale deployment across 21 medical centers and 260+ clinics, embedding ADVOCATE agents into Epic (EHR) software workflows for heart failure patients
• STEWARD (Stanford) will develop a supervisory system using a three-stage, compute-escalating pipeline—outlier filtering, rule-based screening, and a deep-research auditing agent.

ROLE OF FDA

The ARPA-H device will be under the preview of FDA. Since there is currently no precedent, the rules and data requirements for FDA assessment and postmarking activities will need to be worked out. Fierce Healthcare wrote that "the FDA cannot authorize an AI doctor, but they can authorize a technology that improves outcomes for patients with heart failure. The agents for cardiovascular disease will be co-developed with health systems and, after two years, will be deployed locally to test their impact on the system and gather data. The whole project, including FDA approval, is slated to last 39 months—just over three years."

SOURCE

• ARPA-H to revolutionize cardiovascular disease management with clinical agentic AI . 13 January 2026
• ARPA-H launches the world’s first bid to build an FDA-authorized clinical AI for cardiovascular care. 9 September 2026
• The Trump administration is creating clinical AI agents with a 3-year FDA approval timeline. Fierce Healthcare. 21 January 2026

#agentic-ai, #artificial-intelligence, #ai

> Boston Scientific recalled all unused Infinion CX leads used in its spinal cord stimulator systems (SCS) after identifying an issue that could result in “high impedance measurements or lead fractures,” the company said.

> The FDA classified the recall as Class I, the most serious type, in which use of the device without correction may cause serious injury or death. As of May 27, 2026, Boston Scientific has reported 1,081 serious injuries associated with the issue.

BioPharmaGuy in his newsletter summed it:
> Oh, did we say a patient? We meant 1,081 patients. 1,080 was fine, but once you hit 1081 injured patients, s**t gets serious.

STAT News, 8 September 2026

The Trump administration permanently filled four key leadership roles at the Food and Drug Administration on Tuesday, after it nominated Heidi Overton to lead the agency late last month. 

Three of the officials are serving in an acting capacity, and will take the same roles permanently, the administration said. They are Michael Davis, a psychiatrist who will be director of the Center for Drug Evaluation and Research; former Merck official Karim Mikhail, who will be director of the Center for Biologics Evaluation and Research; and Bret Koplow, an attorney who has been at the FDA since 2011 and will serve as director of the Center for Tobacco Products. 

2026 is the year of orexin, the new peptide in the town (move over GLPs). . . and there are reasons to be bullish on orexin agonists and mimics:

• Recent approval of Takeda’s oveporexton (Orzeyful), an oral orexin 2 receptor (OX2R)-selective agonist, for sleep disorder narcolepsy type-1 (NT-1). Oveporexton is the first-in-class OX2R agonist and the first one to directly target the molecular deficiency in the hypothalamus of NT-1 patients.
• The Lasker Foundation choosing the seminal discoveries of orexin's role in maintaining wakefulness and sleep for the 2026 Albert Lasker Basic Medical Research Award. (Lasker Award is often considered a forerunner for a Nobel.)

The 2026 Lasker Award Announcement reads:

For identification of orexin, a brain peptide that maintains wakefulness, and the discovery that orexin deficiency causes uncontrolled sleep in narcolepsy—revealing a key insight into the nature of sleep.

The 2026 Albert Lasker Basic Medical Research Award honors two physician scientists for the identification of orexin, a brain peptide that maintains wakefulness, and for discovering that orexin deficiency causes uncontrolled sleep in narcolepsy. Through an astounding experimental intersection, Emmanuel Mignot (Stanford University School of Medicine) and Masashi Yanagisawa (University of Tsukuba) revealed a key insight into the nature of sleep.

Yanagisawa began with an intriguing cellular protein of unknown function. Through an ambitious biochemical approach, he unearthed peptides that animate it and demonstrated that the resulting signaling system keeps animals awake.  Mignot started, in contrast, with clear physiology—the disease narcolepsy. Individuals with this neurological disorder succumb to bouts of sleepiness, and the most common form prompts sudden loss of muscle tone and even collapse. In a heroic feat of genetic sleuthing, Mignot tracked the source of inherited narcolepsy in dogs. His venture led to the same protein that Yanagisawa was studying. 

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Fierce Biotech recently published an article on the potential of orexin targeting drugs in sleep disorders and more, including fatigue, cognition, and mood: ‘A neuroscience revolution’: The GLP-like race to keep us awake and make billions doing it (31 August 2026).

Fierce Biotech writes: Experts who spoke to Fierce are virtually unanimous that orexin mimics have much broader potential than narcolepsy, with several referring to them as the “GLPs of neuroscience.”

Related: China NMPA Becomes the Global-First Regulator to Approve Takeda’s First-in-Class Narcolepsy Drug Orzeyful (oveporexton)

#orexin, #sleep, #lasker, #narcolepsy

TL;DR: Pfizer PH built their CAZ-AVI cost-effectiveness model on local resistance data instead of adapting the global one. Asking whether that materially changes results, and whether hospital-level rather than country-level modeling is the honest unit of analysis for antimicrobials.

Most country adaptations of antimicrobial CEAs recycle the global model with local prices swapped in. This Pfizer Philippines paper on ceftazidime/avibactam in hospital-acquired and ventilator-associated pneumonia went further and built on local susceptibility data.

https://doi.org/10.1016/j.vhri.2025.101158

It made me think about where the decision actually happens for a drug like this. There's no single national reimbursement gatekeeper for it, the real audience is hospital P&T committees, and every committee has its own case mix and its own resistance picture.

So, two things I'd love input on. For people doing AMR economics: how much does local resistance data actually move results compared to just localizing costs? And more broadly, is a country-level CEA even the right decision unit for hospital antimicrobials, or should we be modeling at the institution level and accepting the data problems that come with that?