COMP Recommends 12 EMA Orphan Drug Designations in July

In July 2026, the number of EMA orphan drug designations recommended by the Committee for Orphan Medicinal Products (COMP) reached twelve, out of twenty-one new applications weighed at its 14-15 July meeting, which was held remotely. Four applications were withdrawn and five were sent a list of issues with an oral explanation set for the next plenary.

On maintenance, COMP recommended that Nezglyal (leriglitazone) stay on the Community Register for adrenoleukodystrophy. Linerixibat in primary biliary cholangitis was sent issues for September, and two other maintenance files were noted only as CHMP status updates.

The policy session drew more interest than usual. COMP was briefed on the use of New Approach Methodologies in 2025 orphan files, on the New Pharma Legislation and the European Health Data Space through the joint PCWP/HCPWP meeting, and on the mid-year 2026 workplan. Those items sit beside a busy rare disease pipeline that spans cell and gene therapy, siRNA, oral somatostatin agonism, and a CAR-T in systemic sclerosis.

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Twelve EMA orphan drug designations recommended

All twelve positive opinions were adopted on the standard Article 3(1)(a)+(b) construction. Where authorised alternatives exist, significant benefit was argued either as a clinically relevant advantage or as a major contribution to patient care, through route of administration, dosing frequency, or inhibitor coverage. Two files needed an oral explanation; for one of them, bimiralisib, the oral was cancelled after the written response.

*Prevalence as estimated by the sponsor and accepted by COMP at the time of the application, persons in the EU. The orphan threshold remains 5 in 10,000.

A few files sat closer to the line. For bimiralisib in thymic epithelial tumours, COMP accepted medical plausibility on in-vitro antiproliferative data plus a single clinical responder, after the sponsor argued that validated in-vivo models of the disease essentially do not exist. The grounds cite no satisfactory treatment in the EU. This is a high-flexibility plausibility decision driven by model scarcity, not by a rich evidence package.

Imsidolimab in generalised pustular psoriasis turned on whether the condition is a distinct medical entity from plaque psoriasis. After the oral explanation, COMP accepted distinctness on IL-36 biology, systemic autoinflammation, and specific criteria, plus rarity at about 3.9 in 10,000, close to the ceiling. Significant benefit was accepted on potentially more sustained flare control, while safety arguments were called premature. The sponsor was advised to take protocol assistance.

Paltusotine framed significant benefit as a major contribution to patient care: oral somatostatin-receptor agonism instead of intramuscular or subcutaneous depot injections, which carry pain, local reactions, and travel burden. The efficacy cited is preliminary reduction of flushing and diarrhoea. Alnylam’s GalNAc-conjugated siRNA in von Willebrand disease rests on quarterly subcutaneous dosing versus IV prophylaxis, plus potential use in patients with inhibitory antibodies to factor replacement.

Zolacabtagene autoleucel, BMS’s CAR-T in systemic sclerosis, drew plausibility from clinical signals in skin and respiratory manifestations. AstraZeneca’s PLN siRNA-bicyclic peptide was renamed by COMP to “treatment of PLN R14del cardiomyopathy”, an ultra-rare file at about 0.14 in 10,000 with no satisfactory method. The anti-activated protein C antibody in haemophilia B lists Parexel Ireland as applicant of record, so the commercial sponsor is not named; its significant benefit sits on comparable annualised bleeding rates with dosing every four weeks rather than daily concizumab, including in patients with inhibitors.

Four withdrawals, one with a recorded debate

The tuberculosis file is the only withdrawal with a reasoned discussion on the record. COMP split the two questions: rarity can still be argued for TB in the EU using current surveillance publications, but significant benefit against a crowded authorised standard of care cannot be carried on early or incomplete comparative data. That is the more transferable lesson.

What this sitting changes

Condition-boundary fights remain live. Generalised pustular psoriasis was accepted as distinct from plaque psoriasis after an oral explanation. Sponsors targeting a severe subset of a common disease still have a path, but they must bring genetics, pathophysiology, diagnostic criteria, and treatment-response differences, rather than severity alone.

Near-threshold prevalence is being used. Generalised pustular psoriasis at 3.9, systemic sclerosis at 3.5, idiopathic pulmonary fibrosis at 3.0, and tuberculosis, accepted below 5 after a methods argument, all sit in the zone where a later maintenance review or an epidemiology update can reopen the file.

Major contribution to patient care is doing real work. Oral paltusotine versus injectable somatostatin analogues, quarterly Alnylam siRNA versus IV factor prophylaxis, and four-weekly anti-APC versus daily concizumab were all accepted on burden-of-administration logic, usually stacked on some efficacy or population-coverage claim.

Significant benefit against a mature standard of care is still the kill point. Tuberculosis had rarity accepted and significant benefit rejected; the sponsor walked rather than take a negative opinion. That pattern will repeat in ALS, haemophilia A, and any infection or oncology file with multiple authorised options.

Model scarcity can substitute for in-vivo packages at designation, but not later. Bimiralisib and the NAM briefing both point COMP toward defined contexts of use for non-animal evidence at the orphan designation gate. Maintenance and marketing authorisation will not be so generous. Gene, RNA, and cell therapy continue to populate the register: AAV6-HCN4 for congenital heart block, the AstraZeneca PLN-targeted siRNA, Alnylam’s GalNAc-siRNA in von Willebrand disease, and the BMS CAR-T in systemic sclerosis. Protocol assistance was explicitly recommended for imsidolimab, and any sponsor whose significant benefit rests on durability, or whose condition definition was contested, should treat that as a signal rather than a courtesy.

Source: Committee for Orphan Medicinal Products, Minutes for the meeting on 14-15 July 2026, EMA/COMP/177879/2026, Human Medicines Division, dated 10 September 2026.