Roxadustat secures December PDUFA date
FibroGen announced on Wednesday that the FDA has accepted its regulatory filing seeking approval of roxadustat for the treatment of anaemia of chronic kidney disease (CKD), in both non-dialysis dependent and dialysis-dependent patients. A PDUFA date for potential approval has been set for December 20.
Roxadustat is being co-developed and will be co-marketed in the US by AstraZeneca under an agreement signed with FibroGen in 2013. Approved already in China and Japan, roxadustat is a closely watched asset in AstraZeneca's pipeline and has been described by Wall Street analysts as a potential blockbuster.
Clinical data indicates that roxadustat is at least as effective as epoetin alpha at treating anaemia while requiring patients to take less iron supplementation. Furthermore, it has been shown to be effective in patients with elevated C-reactive protein levels, which is known to lower response to epoetin. Pooled results suggests that cardiovascular safety for roxadustat is comparable to placebo, though a key part of the FDA's review will be its evaluation of what is considered to be a somewhat complex safety dataset.
Keytruda hits the mark in TNBC
Merck & Co. confirmed this week that the combination of its PD-1 inhibitor Keytruda and chemotherapy has met one its two co-primary endpoints in the Phase III Keynote-355 study by significantly prolonging progression-free survival (PFS) versus chemotherapy alone in first-line patients with metastatic triple-negative breast cancer (TNBC), whose tumours have a PD-L1 expression rate of at least 10%.
Keynote-355 will continue, with a second co-primary endpoint exploring the overall survival (OS) benefit of Keytruda plus chemotherapy versus chemotherapy alone.
Roche's PD-L1 inhibitor Tecentriq is approved in combination with the chemotherapy agent Abraxane for the first-line treatment of TNBC patients with PD-L1 expression of at least 1%; supported by data from the Impassion130 study. Keynote-355 is also evaluating the combination of Keytruda plus chemotherapy in all-comer patients (i.e. regardless of PD-L1 status) and patients with PD-L1 expression of at least 1%, though Merck's press release would appear to insinuate the combination did not meaningfully improve PFS versus chemotherapy alone in either of these cohorts.
Keytruda (with chemotherapy) has previously posted positive data in the Phase III Keynote-522 study, evaluating this combination for the neo-adjuvant treatment of TNBC. By comparison, data was presented at the San Antonio Breast Cancer Symposium (SABCS) in December showing that the addition of Tecentriq to neo-adjuvant chemotherapy in TNBC patients did not meaningfully improve response rates.
Sanofi touts MS hopeful, sheds executives
New CEO Paul Hudson is pushing for meaningful change at Sanofi, which extends from the R&D pipeline to the company's executive committee.
Late last week, alongside the presentation of its fourth-quarter 2019 results, Sanofi made some bullish proclamations about an experimental multiple sclerosis treatment – the BTK inhibitor SAR442168 – which has delivered positive Phase II proof-of-concept data and will now head into a comprehensive pivotal-stage study programme.
Elsewhere at Sanofi, the company confirmed this week that four executives will leave, streamlining the committee that reports into Hudson from 14 to 10. The departures are designed to reflect Sanofi's sharper focus on specialty medicines and vaccines.
Another Alzheimer's disease setback as Biogen nears filing for aducanumab
Roche and Eli Lilly announced this week that results from the Phase II/III DIAN-TU-001 study showed that the experimental drugs gantenerumab and solanezumab did not significantly slow the rate of cognitive decline in patients who have an early-onset, inherited form of Alzheimer's disease, compared with placebo.
The study, which is sponsored by the Washington University School of Medicine, has attracted additional attention in light of the pending regulatory application for another beta-amyloid-targeting antibody, aducanumab, which Biogen expects to file with the FDA in the near future.
It has also been closely watched as researchers identified a concentrated population that they hoped would help push and pull these two therapies – both with multiple failed studies already on their resume – over the statistical hurdle. If successful, this would have provided some much-needed support for the controversial amyloid hypothesis.
Nevertheless, multiple caveats were cited by Wall Street analysts as to why this study failed, and rightly or wrongly, why the result should not influence the FDA's assessment of aducanumab. The most obvious issue is the size of the trial, which enrolled less than 200 patients (due to cost considerations) versus the thousands of patients typically enrolled into late-stage AD studies. Furthermore, the dose of both drugs was significantly increased after new evidence suggested this could increase efficacy, but the change was not implemented until midway through the study.
Bristol-Myers Squibb lines up mid-2020 approval for CAR-T
Since acquiring Celgene last year, Bristol-Myers Squibb has touted its inherited CAR-T therapy lisocabtagene maraleucel (liso-cel; known previously as JCAR017) as a potential best-in-class product. As of Thursday, it can also boast priority view for the agent at the hands of the FDA for the potential third-line treatment of relapsed or refractory large B-cell lymphoma, indicating that it should be approved in the US market by mid-August.
This also has important implications for ex-Celgene shareholders who, as part of the Bristol-Myers Squibb acquisition, received a contingent value right (CVR) linked to the achievement of future regulatory milestones. One of these is approval of liso-cel by the end of 2020.
Data presented at ASH in December suggests that liso-cel has a meaningfully superior side-effect profile versus the approved CAR-T agents Kymriah and Yescarta, which are marketed by Novartis and Gilead Sciences, respectively. This could mean that Bristol-Myers Squibb's entry into the CAR-T space may coincide with more eligible patients being treated in an outpatient setting, one expert told FirstWord on the side-lines at ASH.
Liso-cel's efficacy looks on par with Kymriah and Yescarta, and its manufacturing process is more complex and expensive, though this – designed to yield a treatment that comprises equally of CD4+ and CD8+ T cells – is presumably the reason why it is associated with lower rates of severe cytokine release syndrome and neurotoxicity.
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