Merck's SpringWorks takeover delivers a drug approval

Merck KGaA's acquisition of SpringWorks has only just closed, but has already added a new medicine to its portfolio as it gets an EU approval for rare disease therapy Ezmekly.

The oral MEK inhibitor – already approved in the US as Gomekli (mirdametinib) – has been cleared by the European Commission as a treatment for adults and children aged two and over with neurofibromatosis type 1 who have plexiform neurofibromas (NF1-PN) that cannot be treated with surgery.

NF1 causes tumours to develop on the covering of nerve cells, leading to disfigurement and other debilitating complications like pain, motor dysfunction, and malignant peripheral nerve sheath cancers. There are approximately 135,000 people in the EU living with the condition, according to Merck, and their lifetime risk of developing PN is approximately 30% to 50%. Surgical removal of PN tumours can be challenging due to the tumour growing along nerve fibres.

Ezmekly is the first drug to be approved for children and adults with the genetic disorder in the EU, and the second in the US after AstraZeneca's MEK1/2 inhibitor Koselgo/Koselugo (selumetinib), co-marketed by MSD (known as Merck & Co in the US and Canada).

In Europe, Koselugo – which had global sales of $631 million last year – is cleared for use in children aged three and over only.

The new approval will help Merck make a return on its $3.9 billion investment in acquiring SpringWorks, which has operated as a wholly owned subsidiary since the takeover was completed on 1st July. Some analysts have suggested that peak sales of Gomekli/Ezmekly could top $1 billion.

"Patients with NF1-PN often face physical and mental health challenges and impaired quality of life given the limited treatment options available for this lifelong and debilitating disease," said Ignacio Blanco, chairman of the National Reference Centre for Adult Patients with Neurofibromatosis at Hospital Universitari Germans Trias i Pujol in Spain.

"This approval represents an important advance, especially for adults who previously did not have an approved treatment," he added. "Importantly, [it] is available in a tablet that dissolves easily in water for people who are unable to swallow a pill and could therefore not previously receive therapy." In contrast, Koselugo is formulated as a hard capsule.

In the phase 2b ReNeu trial, mirdametinib showed an overall response rate (ORR) of 41% in adults and 52% in children, with "deep and durable" reduction in the volume of PN lesions, as well as "clinically meaningful" improvements in pain and quality-of-life scores.