Top 10 PNH stories of 2023

Year's coverage included news that crovalimab is under review by FDA

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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This year, PNH News brought up-to-date coverage of the latest scientific and clinical research developments in paroxysmal nocturnal hemoglobinuria (PNH).

Here are the 10 most-read news stories of 2023, along with a brief description of what made them interesting to our readers. We look forward to continuing to be a resource for the PNH community in the new year.

No. 10 – Add-on danicopan may lead to better anemia control

Taking danicopan, an experimental oral medication, may help keep anemia under control in people with PNH who have residual breakdown of red blood cells outside of blood vessels despite being treated with Soliris (eculizumab) or Ultomiris (ravulizumab).

In a Phase 3 clinical trial called ALPHA (NCT04469465), add-on danicopan raised levels of hemoglobin — the protein that carries oxygen in red blood cells — by more than five times over a placebo. Developed by Alexion, AstraZeneca Rare Disease, danicopan is under regulatory review in the U.S. and Europe.

No. 9 – Crovalimab, a C5 inhibitor, may protect red blood cells

Getting monthly injections under the skin of crovalimab, an experimental C5 inhibitor, may protect red blood cells from breaking down while reducing the need for regular blood transfusions.

The medication was seen to keep disease under control for up to four years in adults with PNH who entered an open-label extension to the Phase 1/2 COMPOSER trial (NCT03157635). Crovalimab is being jointly developed by Genentech and Japan-based Chugai Pharmaceutical.

No. 8 – Symptoms of PNH may persist despite using Soliris

Almost three in four people with PNH who received treatment with Soliris at a hospital in Germany over five years continued to have symptoms of the disease. Up to 16% failed to respond to treatment, suggesting that many people with PNH don’t see clinical benefits from AstraZeneca’s Soliris in real-world practice settings.

No. 7 – Ultomiris appears to be safe and effective in real-world practice

The C5 inhibitor Ultomiris appeared to be as safe and to work as well in real-world clinical practice as in clinical trials with controlled protocols. Post-marketing surveillance data from people with PNH in Japan revealed that almost 9% developed an infection, a known risk of treatment with Ultomiris, but in most cases, it was mild.

Ultomiris also helped to prevent red blood cells from being broken down, leading to stable levels of hemoglobin, and reduced the need for blood transfusions, regardless of whether patients had never been treated with a C5 inhibitor or had switched from Soliris.

No. 6 – Cemdisiran may allow for lower doses of Soliris

While cemdisiran, an experimental RNA-based treatment, failed to fully prevent red blood cells from breaking down in adults with PNH who took part in a small Phase 1/2 clinical trial (NCT02352493), it did help reduce the dose of Soliris needed to keep anemia under control.

Cemdisiran is being developed as an under-the-skin treatment by Alnylam Pharmaceuticals. Its use is also being tested when given with another experimental treatment called pozelimab, which works similarly to Soliris.

No. 5 – Empaveli may work better in newly treated PNH patients

People with PNH who began treatment with under-the-skin Empaveli (pegcetacoplan) were more likely to see their hemoglobin increase to stable levels and less likely to have sudden symptoms of the disease than those started on Soliris or Ultomiris.

Empaveli, a complement inhibitor jointly developed by Apellis Pharmaceuticals and Sobi, also appeared to lead to better quality of life for people with PNH than Soliris or Ultomiris. All three treatments were found to have similar benefits on fatigue and physical function.

No. 4 – Fabhalta becomes first FDA-approved oral treatment for PNH

In December, the U.S. Food and Drug Administration (FDA) approved Novartis’ Fabhalta (iptacopan) for adults with PNH, regardless of whether they have been previously treated or have received no prior treatment for their disease. The decision made Fabhalta the first oral medication approved in the U.S. for PNH.

Fabhalta inhibits factor B, a complement protein. This is expected to prevent the breakdown of red blood cells both inside and outside of blood vessels. Because the medication increases the risk of serious infections caused by encapsulated bacteria, patients must complete or update their vaccinations against these bacteria at least two weeks before starting treatment.

No. 3 – Clinical trial of BCX10013 opens in South Africa

A Phase 1 clinical trial (NCT06100900) that’s evaluating the safety and early effectiveness of BCX10013, an experimental oral treatment, is recruiting up to 15 adults with PNH in Cape Town, South Africa. Its sponsor, BioCryst Pharmaceuticals, plans to expand recruitment to other locations where approved medications aren’t widely available to treat PNH.

Those interested in participating in the trial must have never, or at least not recently, received a complement inhibitor. BCX10013 will be tested at four dose levels. It will be given daily for four weeks before the dose can be increased to the next level.

No. 2 – Chugai asks for approval of crovalimab in Japan

In June, Chugai asked Japan’s regulatory body to approve crovalimab, a C5 inhibitor that can be given as an under-the-skin injection at home, to treat PNH. The application was based in part on data from COMMODORE 2 (NCT04434092), a Phase 3 clinical trial that showed crovalimab may work just as well as Soliris for freeing adults with PNH from regular blood transfusions and easing fatigue.

No. 1 – Crovalimab is under FDA review for approval in PNH

The FDA agreed in September to review a biologics license application that Genentech filed seeking approval of crovalimab to treat PNH in the U.S. It’s not known when a final decision will be made, but the FDA typically takes action within 10 months of receiving an application for review. Crovalimab is also under regulatory review in Japan, China, and Europe.


We look forward to continuing to bring you the latest news about PNH in 2024, and we wish all a happy new year!