Planning Moves Upstream: What the P4 Trial Means for CT, IVUS and the Economics of the Cath Lab
Dr. Dereck Mush, MD, MBA
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CARDIOVASCULAR IMAGING AI
1. CT-Guided PCI Planning Matches IVUS in the 1,105-Patient P4 Trial at TCT 2026
Heartflow's PCI Navigator combines coronary CT imaging with anatomical and physiological analysis to support stent planning before catheterization. Image credit: Heartflow.
The P4 trial, presented as a late-breaker at TCT 2026 on November 1 and published simultaneously in NEJM, randomized 1,105 patients with stable coronary disease at 23 centers in the US, Europe and Japan to PCI planned with coronary CT or guided by intravascular ultrasound (IVUS). CT guidance was noninferior for 12-month target-vessel failure: 4.1% vs 4.6%.
The details:
The CT arm used Heartflow's FFRCT Analysis and Heartflow Planner, an earlier version of its PCI Navigator. Median procedure time was 46 vs 63 minutes (17 minutes shorter), median contrast 150 vs 170 mL, and advanced calcium modification was used more than twice as often (9.2% vs 3.8%). Per ACC, median age was 65 and nearly 22% of patients were women.
Principal investigator Carlos Collet, MD, PhD, of the Cardiovascular Research Foundation: "P4 shows that non-invasive CT-guided PCI planning achieves comparable clinical outcomes with shorter procedure times and less contrast, enabling interventionalists to anticipate challenges, tailor their strategy, and enter the cath lab better prepared."
In the separate 203-patient NAVIGATE-PCI registry, physicians changed their plan in about 70% of patients after reviewing PCI Navigator versus angiography alone, most often stent length (41%) and lesion preparation (12%). P4 was investigator-initiated and Heartflow-supported. Heartflow (Nasdaq: HTFL) reports use at more than 1,800 institutions.
The Signal: IVUS earned its place by showing that seeing inside the vessel improves outcomes, but it adds time, cost and skill to every case. P4 says much of that planning can happen before the patient is on the table. That moves value from the cath lab catheter to the CT scanner and the software reading it. The open questions are who pays for planning, and whether the result holds in complex lesions and in hospitals without strong CT programs.
DNA MEDICINES
2. The FDA Approves VOCERYQ, the First Plasmid DNA-Based Immunotherapy in the U.S.
INOVIO's DNA medicine platform uses engineered plasmids and CELLECTRA electroporation technology to deliver genetic instructions into cells. Image credit: INOVIO Pharmaceuticals.
On October 30, the FDA granted accelerated approval to INOVIO's VOCERYQ (previously INO-3107) to reduce the frequency of surgery in adults with recurrent respiratory papillomatosis (RRP), a rare disease in which HPV types 6 and 11 drive wart-like growths in the airway. The FDA calls it the first plasmid DNA-based immunotherapy approved in the U.S.
The details:
VOCERYQ uses DNA plasmids encoding HPV-6 and HPV-11 antigens, plus a second plasmid encoding the immune signal IL-12 per the prescribing information, given by intramuscular injection with INOVIO's CELLECTRA 5PSP device, which uses brief electrical pulses (electroporation) to get the DNA into cells. Four doses, three weeks apart, follow a standard debulking surgery, a 9-week dosing regimen.
In the open-label RRP-001 study of 32 adults, 7 of 26 patients in the efficacy population (27%) needed no surgery in the 12 months after treatment. Those 26 had a median of 4.5 surgeries in the prior year. Because approval is accelerated, the FDA requires a confirmatory study and wants a draft protocol by the end of 2026.
INOVIO expects to take orders and ship in about 60 days, with full field deployment in Q1 2027, supported by Syneos Health. CEO Jacqueline Shea, PhD: VOCERYQ is "designed to deliver what we understand matters most to patients, which is the reduction of the surgical burden caused by RRP." It enters a market where Precigen's PAPZIMEOS won full FDA approval in August 2025.
The Signal: This is a device and a drug approved as one product, and that is the HealthTech story. DNA medicines avoid the viral vectors and lipid nanoparticles that limit other genetic approaches, but they need a delivery device in every clinic that uses them. VOCERYQ arrives second, with a lower published complete response rate than the therapy already on the market and a confirmatory trial still to run. Its case will rest on the patient experience, the delivery logistics and how payers compare the two.
CLINICAL AI
3. Australia's Amended Exemption for Clinical Decision Support Software Takes Effect
An Australian Therapeutic Goods Administration decision chart illustrates how software functionality influences regulatory classification. Amendments to Australia's clinical decision support software exemption took effect on November 1, 2026. Image credit: Therapeutic Goods Administration.
Amendments to the TGA's exemption for clinical decision support software (CDSS) came into force on November 1, under the Therapeutic Goods Legislation Amendment (2026 Measures No. 1) Regulations 2026. Software that meets every criterion is exempt from inclusion on the Australian Register of Therapeutic Goods (ARTG).
The details:
Two new criteria stand out. Exempt software must not be intended to provide a diagnosis or treatment decision, including IVD software. It must also display the guidelines, calculations or logic behind its output, so a health professional can readily interpret and verify the recommendation. The image and signal criterion now names compressing and decompressing alongside processing and analysing.
The TGA says the amendments "do not change the scope of the CDSS exemption or introduce new regulatory requirements." The regulation applies to software made before November 1 that is intended for use on or after it, so there is no transition period. The changes follow a 2024 consultation.
It lands two weeks after the TGA's digital scribe review, published October 16. Of 12 AI scribe products examined, 8 likely meet the medical device definition, 2 need more information and 2 are unlikely to qualify. None of the 12 was on the ARTG, and the TGA declined to say which 8 are likely devices.
The Signal: The new transparency criterion is the one to watch. A rules engine can show its logic. A large language model producing a recommendation mostly cannot, at least not in the readable way the exemption asks for. That pushes generative tools that suggest diagnoses or treatments toward full device regulation, and it gives buyers a simple question to ask any vendor: can my clinician see why it said that?
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