Mirdametinib

GSK's bid to bring back multiple myeloma therapy Blenrep (belantamab mafodotin) got a major boost on Friday when the antibody-drug conjugate (ADC) received a positive opinion from the EU's drug advisory panel. Also receiving a positive vote from the European Medicine Agency's Committee for Medicinal Products for Human Use (CHMP) was Roche's breast cancer drug Itovebi (inavolisib). Survival data for the PI3K inhibitor was recently spotlighted in an abstract released ahead of the American Society of Clinical Oncology (ASCO) meeting (see – ASCO25 abstract roundup: Roche's Itovebi cuts risk of death).Autolus' CAR-T cell therapy Aucatzyl (obecabtagene autoleucel) also received a thumbs up from CHMP, as well as mirdametinib, a MEK inhibitor recently acquired by Merck KGaA in its $3.9-billion takeout of SpringWorks Therapeutics. Blenrep is backBlenrep was withdrawn from global markets in 2022 following disappointing results from a confirmatory trial, but after positive readouts from two pivotal Phase III trials  — DREAMM-7 and DREAMM-8 — GSK has been working to bring the BCMA-targeted ADC back. Specifically, CHMP recommended Blenrep to treat relapsed or refractory multiple myeloma in combination with bortezomib and dexamethasone (BVd) for adults who have received at least one prior therapy; and in combination with Bristol Myers Squibb's Pomalyst (pomalidomide) plus dexamethasone for patients who have received at least one prior treatment, including BMS's Revlimid (lenalidomide).   In DREAMM-7, Blenrep plus BVd achieved a progression-free survival (PFS) of 36.6 months, versus 13.4 months for the comparator regimen of Johnson & Johnson's Darzalex (daratumumab) plus BVd.DREAMM-8 compared Blenrep to bortezomib, both in combination with Pomalyst and dexamethasone. At nearly 22 months follow-up, median PFS was not yet reached with Blenrep compared to 12.7 months in the control arm.In April, the UK became the first country to reauthorise Blenrep. Regulatory applications for the ADC are under review in a dozen other countries, including the US, Switzerland, Japan, China and Canada. The FDA is expected to make a decision by July 23, although there is concern that recent mass layoffs at the FDA could slow down the review process (see – Spotlight On: Could key drug approvals be put at risk of delay by FDA layoffs?).GSK is positioning the drug as a key growth driver, projecting peak annual sales exceeding £3 billion (see – Spotlight On: Can GSK deliver much needed pipeline momentum?).Itovebi impressesItovebi scored a positive opinion for its use in combination with palbociclib and fulvestrant to treat PIK3CA‑mutated, ER‑positive/HER2‑negative, locally advanced or metastatic breast cancer, following recurrence on or within 12 months of completing adjuvant endocrine treatment.The PI3K inhibitor won a similar approval in the US last October based on data from the Phase III INAVO120 study showing a 57% benefit for the Itovebi triplet on the primary endpoint of PFS compared to palbociclib and fulvestrant alone. Patients achieved PFS of 15 months in the experimental arm versus 7.3 months for placebo.At ASCO, Roche plans to share updated survival data for Itovebi. The abstract revealed that patients who received the triplet experienced a median overall survival of 34 months compared to 27 months for controls, representing a 33% reduction in the risk of death. Additionally, the combination therapy delayed the time to chemotherapy from 12.6 months in the control arm to 35.6 months with Itovebi.Go-ahead for Aucatzyl, mirdametinibA CHMP recommendation also went to Aucatzyl to treat patients aged 26 and older with relapsed or refractory B cell precursor acute lymphoblastic leukaemia (ALL).Autolus' CD19-directed cell therapy was cleared by the FDA in November for a similar indication, based on data from the Phase Ib/II FELIX trial. Of 65 patients with ALL who received the CAR-T, 27 (42%) achieved a complete response (CR) within three months, with a median CR duration of 14.1 months.Meanwhile, Merck KGaA's newly gained mirdametinib received a positive opinion to treat symptomatic, inoperable plexiform neurofibromas (PN) in paediatric and adult patients with neurofibromatosis type 1 (NF1) aged 2 years and above. If fully approved by the European Commission, it will have the brand name of Ezmekly.In February, the MEK inhibitor was approved in the US for the same patient population, where it's marketed as Gomekli.

Germany's Merck KGaA has bought out rare disease specialist SpringWorks for $3.9 billion. Connecticut-based SpringWorks is a 2017 spin out of Pfizer. Merck KGaA’s long courtship of SpringWorks Therapeutics has come to fruition as the German drugmaker has bought out the Connecticut biopharma for an equity value of $3.9 billion, the companies said on Monday.The deal, which works out to $47 per share, enhances Merck KGaA’s presence in the U.S. and bolsters its oncology portfolio, as SpringWorks brings two approved drugs and a handful of rare disease pipeline candidates.  When word of the potential acquisition first surfaced in early February, SpringWorks’ share price shot up to $60 and its market cap rose from $3 billion to $4 billion. But as the rumors had cooled by early this month, SpringWorks’ value had returned to its previous level.Then last week came reports of renewed interest from the companies in pulling off the transaction.Merck KGaA said that it paid a premium of 26% based on SpringWorks’ volume-weighted price of $37.38 on February 7, which was the day prior to the initial market speculation about a potential deal.Over the last five days, as deal talks ginned back up, Merck KGaA’s share price has increased by 6%, while that of SpringWorks grew by 21%.In a statement, Merck KGaA CEO Belén Garijo called the buyout “a major step in our active portfolio strategy to position our company as a globally diversified, innovation and technology powerhouse.”Outside of Merck KGaA's electronics business, the SpringWorks deal represents the company's largest acquisition since its 2015 buyout of St. Louis manufacturing specialist Sigma-Aldrich for $17 billion. The German company also acquired Massachusetts manufacturer Millipore for $7 billion in 2010 and Swiss biotech Serono for $13.3 billion in 2006.SpringWorks traces its roots to 2017, when it was spun out of Pfizer with two drugs then in phase 3, which have since been approved. “We have successfully launched two best-in-class medicines in the United States, and with the aspiration to deliver our therapies worldwide, our journey is at a pivotal juncture,” Saqib Islam, CEO of SpringWorks, said in a release. In late 2023, SpringWorks earned an FDA nod for Ogsiveo, a treatment for ultra-rare desmoid tumors. The drug is off to a promising launch, achieving sales of $61 million in the fourth quarter and $172 million for 2024.Two months ago, SpringWorks gained FDA approval for MEK inhibitor Gomekli to treat neurofibromatosis type 1 (NF1), a rare genetic disease. It is the first treatment for adults and children with the disorder and is competing with AstraZeneca and Merck's (U.S.) drug Koselugo, which was approved for pediatric patients and rang up sales of $631 million in 2024. Pipeline candidates brought by SpringWorks include cancer drug brimarafenib, an RAF dimer inhibitor which the company is developing along with BeiGene, and SW-682, a TEAD inhibitor which is being investigated for Hippo-mutant solid tumors.Analysts at ODDO BHF gave the acquisition a thumbs up, writing to clients that it “brings to the healthcare business some positive prospects again.”