Pfizer/Biotech's Covid vaccine data looks good enough for FDA, but parents?

 The devil is often in the detail, and no more so when it comes to balancing the risks and rewards of treating children. As such, Pfizer Biontech’s latest phase 2/3 data in 5-11 year old patients, showing that two 10µg doses of the Covid-19 vaccine Comirnaty stimulated similar antibody responses to 16-25-year-olds might not be enough to convince all parents, especially as there were no data on reduction of serious illness. While children are being hospitalised with the Delta variant, the numbers remain very low, and children, particularly younger children, are still at much lower risk than adults of serious illness and complications following Covid-19 infection. Add to this that mRNA vaccines have been linked to myocarditis – albeit in small numbers – this incidence of which in this age group is almost impossible to gauge from a clinical trial setting. If this latest data divides opinion on whether or not to vaccinate young children, trial results in 2-5 year olds and 6-24 month olds, due at the end of the year, could see those divisions widen further. Pfizer, however, is planning a regulatory filing within weeks, for for a vaccine that Evaluate Pharma forecasts will make $31.8bn this year, a consensus figure that looks likely to rise with the prospect of boosters for adults. 

Selected paediatric Covid-19 trials
Project	Company/Sponsor	Trial	Age (years)	Enrolment
Comirnaty (BNT162b2)	Biontech/Pfizer	NCT04368728	12 - adult	43,998
Comirnaty (BNT162b2)	Biontech/Pfizer	NCT04816643	6 months - 11 years	4,500
Ad26.COV2-S	J&J	NCT05007080	12-17	4,350
Spikevax	Moderna/BARDA	NCT04649151	12-17	3,732
Nanocovax	Nanogen	NCT04683484	12 - adult	620
SARS-CoV-2 vaccine	Sinovac	NCT04551547	3-17	552
Covaxin (BBV152)	Bharat Biotech	NCT04471519	12 - adult	755
Vaxzevria (AZD1222)	Astrazeneca/Oxford Uni	COV006	6-17	300
Source: Evaluate Pharma, clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/snippets/pfizerbiotechs-covid-vaccine-data-looks-good-enough-fda-parents

Mirati moves for an independent future

 Stronger than expected response rates with Mirati’s Kras inhibitor adagrasib in colorectal cancer, unveiled at Esmo this weekend, had analysts speculating about accelerated approval. Today executives confirmed this plan, telling investors that FDA talks will be held before year end. Mirati believes that data in around 100 patients, in both combination and monotherapy settings, will be required. Another big unveiling today concerned the first look at phase 2 lung cancer data, and a 43% response rate should please. This puts adagrasib in the same ballpark as Amgen’s Lumakras, which was approved on a 36% ORR; Kras G12C-mutant NSCLC will form Mirati’s other accelerated approval application before year end. Full presentation of this data remains important, however, including a closer look at safety. The company promised this in early 2022. This means a busy period awaits new chief executive David Meek, a surprise appointment that also emerged today. The former Ipsen boss's mixed track record notwithstanding, some could be disappointed that Mirati is “building up” rather than seeking a sale or partnership, the prospect of which remains the bull case for many investors. With the stock opening 9% higher, those considerations are apparently for another time.

Cross-trial comparison of Kras inhibitors in second-line+ KRAS G12C-mutated NSCLC
	Adagrasib: Krystal-1		Lumakras: Codebreak 100
	Ph 2 cohort 600mg BID (n=?) (registrational)	Ph1/1b cohort 600mg BID (n=19)  (not registrational*)	960mg QD (n=124)
ORR	43%	58%	36%
mDoR	?	12.6 months	10 months
mPFS	?	8.3 months	6.8 months
*Investigator assessed. ORR= overall response rate; mDoR= median duration of response; mPFS=median progression free survival. Source: company press releases, drug label.

Building for an independent future? Mirati's near term plans

Source: Mirati investor presentation.

https://www.evaluate.com/vantage/articles/news/snippets/mirati-moves-independent-future

Genentech: Late-stage Trial Data Support Benefit Of Tecentriq In Early-stage Lung Cancer

 Genentech, a member of the Roche Group (RHHBY), said it presented new data from the Phase III IMpower010 study at the European Society for Medical Oncology Congress 2021 Presidential Symposium. The data reinforce the significant disease-free survival or DFS benefit offered by Tecentriq (atezolizumab) for people with Stage II-IIIA non-small cell lung cancer or NSCLC whose tumors express PD-L1=1%.

Data from the IMpower010 trial were published simultaneously in The Lancet.

In the study, treatment with Tecentriq, following surgery and chemotherapy, reduced the risk of disease recurrence or death (DFS) by 34% in people with Stage II-IIIA NSCLC whose tumors express PD-L1=1%, compared with best supportive care (BSC). Safety data for Tecentriq were consistent with its known safety profile and no new safety signals were identified.

The U.S. Food and Drug Administration recently granted Priority Review to Tecentriq as an adjuvant treatment for certain people with early NSCLC and is reviewing the application under the Real-Time Oncology Review pilot program, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. The FDA is expected to make a decision on approval by December 1, 2021.

https://www.nasdaq.com/articles/genentech-%3A-late-stage-trial-data-support-benefit-of-tecentriq-in-early-stage-lung-cancer

Bristol skin cancer combo to get FDA priority review

 Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has accepted for priority review the Biologics License Application (BLA) for the LAG-3-blocking antibody relatlimab and nivolumab fixed-dose combination, administered as a single infusion, for the treatment of adult and pediatric patients (12 years and older and weighing at least 40 kg) with unresectable or metastatic melanoma. The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of March 19, 2022.

https://finance.yahoo.com/news/u-food-drug-administration-accepts-105900488.html

Synlogic: Positive Phase 2 Data in Patients with Phenylketonuria

  SYNB1618 demonstrated proof of concept with meaningful reduction of plasma phenylalanine (Phe) levels in an interim analysis of the Phase 2 SynPheny-1 Study --

-- SYNB1934, an optimized strain of SYNB1618, demonstrated two-fold increase in biomarkers of Phe metabolism compared to SYNB1618 --

-- Phase 2 SynPheny-1 study will incorporate SYNB1934. Company to prepare to start Phase 3 program with the most promising strain in Phenylketonuria (PKU) in 2022 --

-- Conference call and webcast to discuss results at 8:30 AM --

Conference Call & Webcast Information

Synlogic will host a conference call and live webcast at 8:30 a.m. ET today, Monday, September 20, 2021. To access the live webcast, please visit the "Event Calendar" page within the Investors and Media section of the Synlogic website. Investors may listen to the call by dialing +1 (844) 815-2882 from locations in the United States or +1 (213) 660-0926 from outside the United States. The conference ID number is 1154745. A replay will be available for 30 days on the Investors and Media section of the Synlogic website.

https://finance.yahoo.com/news/synlogic-announces-positive-phase-2-103000006.html

Verastem, Amgen partner on lung cancer combo

 Verastem Oncology (Nasdaq:VSTM), a biopharmaceutical company committed to advancing new medicines for patients battling cancer, today announced a clinical collaboration agreement with Amgen to evaluate the combination of VS-6766, Verastem Oncology’s investigational dual RAF/MEK inhibitor, with Amgen’s KRAS G12C inhibitor LUMAKRASTM (sotorasib) in KRAS G12C-mutant non-small cell lung cancer (NSCLC).

The Phase 1/2 trial will evaluate the safety, tolerability and efficacy of VS-6766 in combination with LUMAKRASTM in patients with KRAS G12C-mutant NSCLC who have not been previously treated with a KRAS G12C inhibitor as well as in patients who have progressed on a KRAS G12C inhibitor. The study will therefore investigate the potential benefits of a more complete vertical blockade of the RAS pathway with the combination of VS-6766 (RAF/MEK blockade) with LUMAKRASTM (G12C inhibition) in KRAS G12C-mutant locally advanced or metastatic NSCLC.

"Recent data indicate that acquired resistance to KRAS G12C inhibitors in patients occurs predominantly through additional mutations in the RAS pathway, many of which may be addressed with a downstream inhibitor such as VS-6766,"1 said Ramaswamy Govindan, M.D., Professor, Department of Medicine, Oncology Division at Washington University School of Medicine and lead investigator of the study. "This clinical study of VS-6766 and LUMAKRASTM will build on preclinical data showing synergy between these two agents, including tumor regression through deeper blockade of ERK pathway signaling."

https://finance.yahoo.com/news/verastem-oncology-amgen-partner-evaluate-110000301.html

Edesa: Positive Phase 2 Data on Monoclonal Antibody in Hospitalized COVID-19 Patients

 

• Study unblinded due to strong efficacy signalfor 28-day mortality endpoint

• Critically ill patients demonstrated a 68.5% reduction in the risk of dying when treated with EB05 over Standard of Care

• Data monitoring board recommends continuation to confirmatory Phase 3 study

https://finance.yahoo.com/news/edesa-biotech-announces-positive-phase-120000255.html