Abemaciclib

Roche said Tuesday that yet another late-stage study of giredestrant hit its efficacy mark at a pre-planned interim analysis, marking the first time a selective oestrogen receptor degrader (SERD) has demonstrated significant benefit in the adjuvant setting for patients with early-stage, oestrogen receptor (ER)-positive, HER2-negative breast cancer.The Phase III lidERA trial enrolled over 4100 patients with medium- or high-risk stage I-III disease. Participants were randomised to receive adjuvant giredestrant or standard-of-care endocrine therapy, the primary endpoint being invasive disease-free survival (DFS) excluding second primary non-breast cancers.Top-line findings showed the trial’s main goal was met, with giredestrant showing statistically significant, clinically meaningful invasive DFS benefit over endocrine therapy at the interim analysis. Roche noted that while the overall survival data were immature at the time, a clear positive trend was observed.Emphasising the fact that ER-positive patients account for up to 70% of breast cancer cases and a high rate of recurrence on or after adjuvant endocrine therapy, Levi Garraway, Roche's chief medical officer, said the “results underscore the potential of giredestrant as a new endocrine therapy of choice for people with early-stage breast cancer, where there is a chance for cure."Safety-wise, giredestrant was well tolerated, with adverse events consistent with its known profile and no unexpected findings. Detailed data will be presented at an upcoming medical conference and also shared with regulatory agencies.Gaining momentumThis lidERA results represent the second positive Phase III readout for the oral SERD, following the pivotal evERA data in advanced disease unveiled at this year’s European Society for Medical Oncology (ESMO) congress. The latest findings are further bolstered by prior neoadjuvant findings from the mid-stage coopERA trial, which demonstrated giredestrant's superiority over aromatase inhibitors in lowering Ki67 levels.Beyond evERA and lidERA, the Roche drug is in three other late-stage trials: with Pfizer’s Ibrance (palbociclib) in endocrine-sensitive recurrent advanced disease in persevERA, due to read out next year; with a CDK4/6 inhibitor in endocrine-resistant advanced disease; and with Phesgo (pertuzumab/trastuzumab/hyaluronidase) in ER+/HER2+ advanced breast cancer.However, competition for giredestrant is intensifying, with Lilly’s imlunestrant, alone or with Verzenio (abemaciclib) clearing the Phase III EMBER-3 trial, while AstraZeneca’s camizestrant — being explored in SERENA-4 and SERENA-6 studies — is projected to reach $6 billion in peak sales. Meanwhile, Pfizer and Arvinas’ PROTAC SERD vepdegestrant is under FDA review even as the partners seek to out-license it.Despite oncology not being a major long-term growth driver for Roche, it remains committed to key breast and lung cancer assets — including giredestrant, which it expects to be a CHF 3 billion-plus opportunity. (see – Vital Signs: Roche's shift from 'minor' disease settings to the big leagues).

Barely a month after joining Merck & Co. through a $10-billion merger, Verona Pharma has withdrawn its EU marketing application for Ohtuvayre (ensifentrine), the inhaled PDE3/4 inhibitor touted as a key addition to Merck's cardio-pulmonary portfolio. The filing was pulled on Oct. 30 as the European Medicines Agency (EMA) was still evaluating initial information from the company, leaving the review process unfinished and without any recommendations from the regulator. Ohtuvayre was approved in the US last year for maintenance treatment of chronic obstructive pulmonary disease (COPD), supported by two Phase III trials demonstrating significant lung function improvements in patients with moderate-to-severe illness. Review of priorities However, the studies did not enroll COPD patients exacerbating on triple therapy, a group where some pulmonologists think it is likely to be used most often. In a recent FirstWord interview, one key opinion leader (KOL) described Ohtuvayre as effective and meaningfully safer than roflumilast, but suggested that this data gap in triple-therapy patients was likely to impact how often it will be used. For more, see – KOL Views Q&A: Leading expert impressed by Ohtuvayre but sees one feature weighing on use in COPD. According to the EMA, Verona stated that it withdrew the Ohtuvayre application "following a review of its priorities." Positive recommendations While Ohtuvayre's EU prospects appear to be on pause, the EMA's Committee for Medicinal Products for Human Use (CHMP) issued a number of positive opinions for other therapies on Friday. Nearly three months after getting the all-clear in the US, Ionis and Otsuka's Dawnzera (donidalorsen) received a CHMP recommendation for routine prevention of recurrent hereditary angioedema attacks in adults and adolescents aged 12 and older. The RNA-targeting prophylactic, administered subcutaneously once a month, is backed by Phase III data from the OASIS-HAE study showing it led to a mean 81% reduction in HAE attacks versus placebo. Otsuka holds exclusive rights to market Dawnzera across Europe and the Asia-Pacific region. CHMP also issued a positive opinion for Eli Lilly's Inluriyo (imlunestrant), an oral selective oestrogen receptor degrader (SERD) aimed at adult patients with locally advanced or metastatic breast cancer and an activating ESR1-mutation. The drug was approved by US regulators in September based on data from the Phase III EMBER-3 trial showing it lowered the risk of progression or death by 38% over standard endocrine therapy in ESR1-mutant patients. The risk-reduction rate ticked up to 43% when Inluriyo was given alongside Lilly's CDK4/6 inhibitor Verzenio (abemaciclib), compared to SERD alone (see – KOL Views Q&A: Battle for oral SERD supremacy in HR+ breast cancer boils down to efficacy). Sanofi's Teizeild (teplizumab) secured a favourable recommendation as a therapy intended to preserve beta-cell function and delay progression to stage 3 type 1 diabetes (T1D) in adults and children 8 years and older with stage 2 disease. In clinical testing, median time to onset of stage 3 T1D was 49.5 months with Teizeild versus 24.9 months for placebo. Sanofi gained the drug — marketed in the US as Tzield and approved there three years ago — through its nearly $3 billion takeout of Provention Bio in 2023. Meanwhile, Waskyra (etuvetidigene autotemcel) became the first gene therapy to receive a positive CHMP opinion for Wiskott-Aldrich syndrome, a rare immunodeficiency that almost exclusively affects males and can lead to bleeding problems and eczema as well as susceptibility to infections. Data from a clinical development programme involving 27 patients showed that Waskyra reduced both severe infections (from 2.0 to 0.12 annual events by years 2-3) and moderate-to-severe bleeding episodes (from 2.0 to 0.16 annual events by years 2-3) compared to pre-treatment rates. If authorised, Waskyra would offer an alternative for patients who are candidates for stem-cell transplantation, but lack suitable donors. The applicant is Fondazione Telethon ETS, which also submitted a filing to the FDA earlier this year. Anavex craters The news was less upbeat for Anavex Life Sciences, however, after EU regulators delivered a negative trend vote on its marketing application for blarcamesine in early Alzheimer's disease, signaling that the agency is likely to issue an unfavourable opinion when it meets in December. According to Anavex, the orally available drug candidate is designed to restore cellular homeostasis by targeting SIGMAR1 and muscarinic receptors. The regulatory setback triggered a sharp investor reaction, with Anavex shares falling roughly 38% on Friday. The company says it plans to seek a formal re-examination once the opinion is formally adopted, a process that would shift review to a separate CHMP panel and allow Anavex to submit additional biomarker analyses. The EU filing included data from the Phase IIb/III ANAVEX2-73-AD-004 trial showing that once-daily oral blarcamesine slowed clinical progression by 36.3% at 48 weeks — and by nearly 50% in patients with the prespecified SIGMAR1 wild-type genotype — on the primary ADAS-Cog13 cognitive measure. Separately, Anavex said Friday that the FDA has advised the company to schedule a meeting to discuss clinical results from its Alzheimer's trials.