6-7 - News

The long-term data, from the phase 3 KEYNOTE-024 trial, demonstrated that treatment with Keytruda led to a sustained survival benefit and durable responses, when compared to chemotherapy in PD-L1-positive non-small cell lung cancer.

At the five-year time point, the overall survival rate for patients receiving Keytruda was twice as high compared to chemotherapy (31.9% and 16.3% respectively). The checkpoint inhibitor also reduced the risk of death by 38% versus chemotherapy, with a median overall survival rate of 26.3 months for Keytruda compared to 13.4 months for placebo.

Amivantamab is being investigated in combination with lazertinib as a treatment for NSCLC patients with epidermal growth factor receptor (EGFR) exon 19 deletions or L858R mutations.
The CHRYSALIS study investigators assessed the efficacy of the combination treatment using overall response rate (ORR) markers, as well as clinical benefit rate, duration of response and the safety profile of amivantamab plus lazertinib in 91 patients.

The results showed promise in this patient population, with patients in the treatment-naïve group achieving a 100% ORR.

In a group of 45 patients who had relapsed following treatment with AstraZeneca’s Tagrisso (osimertinib), Janssen’s combination treatment produced a 36% ORR, with one complete response and 15 partial response, representing a clinical benefit rate of 60%.

Tagrisso (osimertinib) demonstrated a clinically meaningful improvement in central nervous system disease-free survival in the treatment of early-stage EGFR-positive non-small cell lung cancer.
These detailed results showed that fewer patients treated with Tagrisso in the adjuvant setting had a recurrence event or death compared to placebo – 11% and 46% respectively.

For those patients whose cancer did recur, 38% had a metastatic recurrence, compared to 61% of patients on the placebo arm. Tagrisso treatment also reduced the risk of CNS recurrence or death by 82%.

The results detailed a 40% reduction in the risk of death among previously untreated renal cell carcinoma patients receiving Opdivo (nivolumab) plus tyrosine kinase inhibitor Cabometyx (cabozantinib) compared to Pfizer’s older drug Sutent (sunitinib). According to Bristol Myers Squibb, the benefit applied to all patients regardless of their PD-L1 status.

The combo also met the primary trial endpoint of achieving a statically significant improvement in progression-free survival, with Opdivo plus Cabometyx hitting a median PFS of 16.6 months compared to 8.3 months for Sutent.

The phase 3 PROfound trial studied Lynparza in men with metastatic castration-resistant prostate cancer with BRCA 1/2 or ATM gene mutations versus new hormonal agent treatments enzalutamide or abiraterone.

In the key secondary endpoint of overall survival, Lynparza reduced the risk of death by 31% compared to enzalutamide or abiraterone. Median overall survival was 19.1 months for Lynparza, versus 14.7 months for the new hormonal agent treatments, which is particularly noteworthy given that 66% of men receiving enzalutamide or abiraterone had already begun using Lynparza following progression of their disease.

The transaction will see Gilead purchase Immunomedics for $88 per share, for a total value of $21bn, and is expected to close during the fourth quarter of the year. It will be funded by around $15bn in cash, with the remaining $6bn being offered in newly issued debt.

Following the acquisition, Gilead gains rights to Immunomedics antibody-drug conjugate (ADC) Trodelvy (sacituzumab govitecan-hziy), which was approved by the US Food and Drug Administration (FDA) in April for the treatment of metastatic triple-negative breast cancer (mTNBC). Immunomedics is also seeking approval in the EU for Trodelvy in the first half of 2021.

Trodelvy significantly improved both progression-free survival and overall survival in the phase 3 ASCENT study, which evaluated the drug in previously treated mTNBC patients. The detailed results are expected to be presented at the upcoming European Society for Medical Oncology (ESMO) Virtual Congress 2020.

The ADC is also being studied in an ongoing phase 3 trial in third line HR+/HER2-positive breast cancer, and a registrational phase 2 study in bladder cancer. Immunomedics is also testing Trodelvy’s potential in non-small cell lung cancer as well as other solid tumour types, as both a monotherapy and in combination with checkpoint inhibitors.

Gilead has been bolstering its oncology portfolio over the course of this year, with prior deals including a play for Tizona Therapeutics and its lead antibody candidate, as well as its all-cash deal for Forty Seven.

In its agreement with Vertex, Moderna will receive $75m to collaborate on the research and development into gene therapies for CF. As part of the deal, Moderna will discover and develop lipid nanoparticles (LNPs) and mRNAs for the delivery of gene-editing therapies for the treatment of CF.

Under the terms of the deal, Moderna will receive $75m upfront to conduct research activities to discover and develop LNPs for gene-editing CF therapies. The US-based biotech company will also be eligible to receive up to $380m in further development, regulatory and commercial milestone payments, as well as tiered royalties on any products that come out of the collaboration.
While Moderna will be responsible for the initial discovery and manufacturing of LNPs and mRNA constructs for the gene-editing treatments, Vertex will be responsible for providing other components of the therapies to be formulated into LNPs, as well as the preclinical and clinical development and commercialisation efforts of any potential candidates.

This is the second agreement reached between Moderna and Vertex, with the previous collaboration aimed at the discovery and development of mRNA therapeutics for CF having been recently extended.

Prior to announcing the Vertex deal, Moderna revealed that it had come to a separate agreement with Italian-domiciled pharma company Chiesi, for the development of mRNA treatments for PAH.
As part of that deal, Moderna will receive $25m upfront as well as a potential $400m in milestone payments to conduct research and development activities in this therapy area.

The PRIME designation for LentiGlobin was based on a clinical data package from the completed phase 1/2 HGB-205 study, as well as the ongoing phase 1/2 HGB-206 study and long-term safety and efficacy follow-up LTF-303 study.

LentiGlobin is designed to add functional copies of a modified form of the β-globin gene, which does not work as it should in sickle cell patients, into haematopoietic stem cells.

After patients receive copies of the functional gene, their own red blood cells can produce anti-sickling haemoglobin which decrease the amount of faulty sickled haemoglobin in the blood.

In the HGB-206 study, LentiGlobin achieved a near complete elimination of vaso-occlusive crises (VOCs) and acute chest syndrome (ACS) in adolescents and adults with sickle cell disease, along with a 99.5% reduction on the annualised rate of 14 patients with a documented history of attacks.
Researchers also followed up the patients for up to two years, showcasing the potential durability of LentiGlobin treatment. The therapy also increased the proportion of the anti-sickling form of haemoglobin (HbAT87Q) from 44% of total haemoglobin at six months to more than 50% among patients treated 24 months previously.

The PRIME initiative provides enhanced support partnered with an intent to optimise development plans and accelerate regulatory evaluations for potentially transformative therapies.
LentiGlobin is approved under the brand name Zynteglo in Europe for the treatment of dependent beta thalassaemia (TDT) in patients who do not have a matching donor for a stem cell transplant.

Round-up of news from the 2020 European Society for Medical Oncology (ESMO) virtual congress

Gilead agrees $21bn buyout of Immunomedics

Moderna signs R&D agreements with Vertex and Chiesi

EMA fast-tracks review of bluebird bio’s LentiGlobin for sickle cell disease