Five years, one rejection, 28 patients: the FDA approves a first drug for TA-TMA

Transplant-associated thrombotic microangiopathy is a complication of stem cell transplantation in which small blood vessels clot, red cells shear apart on the damage, platelets are consumed, and organs — most often the kidneys — fail. It has had no approved treatment.

On 23 December the US Food and Drug Administration approved one. Yartemlea (narsoplimab-wuug), a MASP-2 inhibitor made by Omeros Corporation, is indicated for the treatment of adult and paediatric patients two years of age and older with haematopoietic stem cell transplant-associated thrombotic microangiopathy [s1][s2].

The approval is worth reading closely, because the evidence supporting it is unusually small even by rare disease standards, and the regulatory history behind it is unusually long.

The path

The biologics licence application was received on 17 November 2020 [s1].

The FDA issued an action letter on 15 October 2021 [s1]. Omeros submitted a resubmission dated 26 March 2025 that constituted a complete response to it [s1]. Major amendments dated 20 and 27 May 2025 extended the goal date by three months [s1].

US License No. 2141 was issued to Omeros Corporation of Seattle [s1]. The FDA's application record classifies the original submission as a priority review of a Type 1 new molecular entity, approved 23 December 2025 [s1].

Five years and one rejection between filing and approval, for a condition with nothing else on the label.

The evidence

Efficacy was assessed in two data sources [s2].

The first is a single-arm, open-label study — referred to in the label as the TA-TMA Study — that enrolled 28 adult patients who developed TA-TMA after haematopoietic stem-cell transplantation [s2]. Twenty-four received 4 mg/kg intravenously once weekly and four received 370 mg intravenously once weekly [s2].

The second is a global expanded access programme. That programme treated 221 adult and paediatric patients in total, but patient-level response data were available for only 19 of them — 13 adults and six children [s2].

So the efficacy dataset is 28 plus 19: 47 patients with evaluable response data, from a programme that treated 249 in all [s2].

Across the 28 study patients and 19 EAP patients, the median number of administrations was 8 (range 2–34), and the median duration of therapy was 8 weeks (range 2–16 weeks) [s2].

What "response" meant

The primary efficacy assessment was TMA response, defined as improvement in both of two laboratory markers — lactate dehydrogenase and platelet count — plus either improvement in organ function or independence from transfusions [s2]. LDH improvement required levels below 1.5 times the upper limit of normal [s2]. The same criteria were applied to both datasets [s2].

TA-TMA response was achieved in 17 of 28 patients (61%, 95% CI 40.6–78.5) in the study, and in 13 of 19 (68.4%) in the expanded access programme — 4 of 6 paediatric patients (67%, 95% CI 22.3–95.7) and 9 of 13 adults (69%, 95% CI 38.6–90.9) [s2].

Within the study, improvement in organ function was seen in 20 of 27 patients (74%), and freedom from red blood cell or platelet transfusion in 12 of 25 (48%) [s2].

The confidence intervals are the story. A paediatric response rate of 67% with an interval running from 22.3% to 95.7% [s2] is compatible with almost anything.

The absent comparator

There is no control arm anywhere in this package [s2].

TA-TMA in these patients was severe. In the study cohort, 96% had organ dysfunction, 75% renal dysfunction, 57% neurological dysfunction, 86% had an infection, and 68% had grade II–IV acute graft-versus-host disease [s2]. Median age was 48 years (range 22–68) [s2]. Median time from transplant to TMA diagnosis was 73.5 days (range 21–436) and median time from TMA diagnosis to first dose was 13.5 days (range 4–196) [s2].

Patients in the expanded access programme were treated far sooner after diagnosis — median 3 days (range 0–52) versus 13.5 days in the study [s2] — which is one plausible reason their response rate was higher, and which a single-arm design cannot separate from drug effect.

Laboratory markers can also improve for reasons unrelated to a drug: resolution of the triggering infection, control of graft-versus-host disease, withdrawal of calcineurin inhibitors, or the natural course in patients who were going to recover. A single-arm study measuring biochemical response cannot exclude any of them. Whether it should nonetheless suffice in a disease with no approved therapy is a judgement the agency has made here, not a scientific question the data answer.

The safety profile

The label carries one warning: serious infections [s2].

Serious infections, independent of causality, were reported in 36% of TA-TMA patients receiving the drug in clinical trials — 10 of 28 — including sepsis, viral infections, pneumonia, bacteraemia, fungal infection, gastroenteritis, respiratory tract infection and urosepsis [s2].

Serious adverse reactions of any kind were reported in 61% of patients [s2]. Those occurring in more than 5% were acute kidney injury, confusional state, acute respiratory failure, neutropenic sepsis, septic shock, pulmonary oedema and vomiting [s2]. Fatal adverse reactions occurred in 7% of patients, including neutropenic sepsis and septic shock [s2].

The most common adverse reactions at more than 20% incidence, without regard to causality, were viral infections, sepsis, haemorrhage, diarrhoea, vomiting, nausea, neutropenia, pyrexia, fatigue and hypokalaemia [s2]. Haemorrhage was the most frequent single entry, at 43% [s2].

These are patients in the weeks after a stem cell transplant, so a large share of that would occur without any drug — which is exactly why the numbers are presented in the label independent of causality, and exactly why a 28-patient uncontrolled cohort cannot apportion them. The 7% fatal adverse reaction rate is the figure that most needs a control arm and does not have one [s2].

No new clinically significant safety signals were identified among the 221 expanded access patients, who received a median of 8 doses over a median 5.5 weeks [s2].

There are no contraindications listed [s2].

Dosing

For patients weighing 50 kg or more, 370 mg by intravenous infusion over 30 minutes once weekly, with the frequency increased to twice weekly if TA-TMA signs and symptoms do not improve adequately [s2]. For patients under 50 kg, 4 mg/kg on the same schedule and the same escalation rule [s2]. It is supplied as 370 mg/2 mL (185 mg/mL) in a single-dose vial [s2].

Manufacturing is split across continents: drug substance at Lonza Biologics Tuas Pte. Ltd. in Singapore, final formulated drug product at Vetter Pharma-Fertigung GmbH & Co. KG in Langenargen, Germany [s1].

Why it matters

TA-TMA has been managed off-label, inconsistently, with supportive care and borrowed complement inhibitors. An approved product with a defined dose and a label changes that, and it makes paediatric use — down to age two — explicit [s2].

It also illustrates what regulatory flexibility in rare disease actually looks like in numbers: a 61% response rate on a composite laboratory endpoint in 28 uncontrolled patients, supported by 19 more whose data were retrieved from a compassionate-use programme [s2]. That is a defensible decision and a thin evidence base, and both statements are true at once.

What to watch

Whether any randomised or externally controlled study of narsoplimab in TA-TMA is undertaken, whether post-marketing data separate the drug's infection risk from the transplant's, and how the FDA's review documents — due for posting in 2026 — describe the reasoning behind the 2021 action letter and its reversal.

This article is informational and is not medical advice.

Sources

• [s1] US Food and Drug Administration. "BLA 761152 Approval Letter — YARTEMLEA (narsoplimab-wuug) injection." 23 December 2025; letter posted 29 December 2025. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/761152Orig1s000ltr.pdf
• [s2] US Food and Drug Administration. "YARTEMLEA (narsoplimab-wuug) injection, for intravenous use — Highlights of Prescribing Information." Revised 12/2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761152Orig1s000lbl.pdf