Gilead's Kite Applies to FDA for Earlier Use of Yescarta in Large B-cell Lymphoma

 Kite, a Gilead Company (Nasdaq: GILD), today announced that it has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for Yescarta® (axicabtagene ciloleucel) to expand its current indication to include the treatment of adults with relapsed or refractory large B-cell lymphoma (LBCL) in the second-line setting.

The sBLA filing is based on data from the ZUMA-7 study with the longest follow-up – over two years – of any Phase 3 CAR T-cell therapy trial. Top-line results from the primary analysis of ZUMA-7 were recently reported and showed superiority of Yescarta compared to standard of care (SOC) in second-line relapsed or refractory LBCL. With a median follow-up of two years, the study met the primary endpoint of event-free survival (EFS; hazard ratio 0.398, p <0.0001). This represents a clinically meaningful 60% reduction in risk of EFS events versus standard of care. The study also met the key secondary endpoint of objective response rate (ORR). The interim analysis of overall survival (OS) showed a trend favoring Yescarta; however, the data are immature at this time, and further analyses are planned for the future.

https://www.streetinsider.com/Corporate+News/Gileads+%28GILD%29+Kite+Submits+sBLA+to+FDA+for+Earlier+Use+of+Yescarta+in+Large+B-cell+Lymphoma/19007979.html

FDA posts guidance on mining real-world data from health records

 There is a lot of discussion about the power of drawing out insights from information hidden within electronic health records and insurance claims, but little regulatory guidance on how that should be undertaken.

Now, the FDA has published its first take on sourcing real-world data (RWD) from EHRs and medical claims, setting out its thinking on the approach that should be used to support regulatory filings for medicines.

The new guidance is the first of a series that have been promised by the US regulator to develop a framework for regulating RWD, which is increasingly being used by pharma companies to investigate how their medicines perform beyond the controlled environment of clinical trials.

The plan is in response to new legislation requiring the FDA to create a framework for evaluating real-world evidence (RWE) to support the approval of a new indication for an already-approved drug, or other post-approval study requirements, for example to provide confirmatory data after an accelerated approval.

In some respects the agency is playing catch-up in this area, as it has already approved the first new indication for a drug based on real-world evidence (RWE) alone – a filing to expand the breast cancer indication for Pfizer’s Ibrance (palbociclib) to include men in 2019.

It is becoming increasingly common for pharma companies to include some element of RWE in their marketing applications to back up clinical trial results.

The new guidance – entitled Real-World Data: Assessing Electronic Health Records and Medical Claims Data to Support Regulatory Decision-Making for Drug and Biological Products – covers three key issues related to the use of RWD from EHRs and medical claims data.

First up is advice on how to select and validate data sources that appropriately address the study question in terms of study populations, exposure, outcomes of interest, and other factors.

It also focuses on the development and validation of definitions for study design elements, and maintaining the provenance and quality of data during  “accrual, curation, and transformation into the final study-specific dataset. ”

The guidance does not provide recommendations on study designs or statistical analyses, or any particular type of data source or study methodology, but instead seeks to set out general principles on RWD use.

“For all study designs, it is important to ensure the reliability and relevance of the data used to help support a regulatory decision, ” says the regulator.

The FDA stresses it is a preliminary document and is encouraging comments, which can be filed up to 60 days after publication.

https://pharmaphorum.com/news/fda-posts-guidance-on-mining-real-world-data-from-health-records/

Glaxo $4.2B bet on Merck KGaA cancer drug goes up in smoke after series of flops

 Merck KGaA and GlaxoSmithKline are ending a partnership for the oncology asset bintrafusp alfa which could have netted billions for the German pharma if successful.

But the data just didn’t pan out that way in multiple tests, most recently a phase 2 clinical trial in locally advanced or metastatic biliary tract cancer that was discontinued due to futility.

The companies announced their mutual parting effective today, September 30. Merck said the decision was “based on the clinical trial data generated to date,” specifically results from the INTR@PID Lung 037 study that failed to show the effect seen in earlier tests.

GSK did not pay out any milestone payments through the deal and will not do so in the future, either. Merck collected €300 million upfront in 2019 through the pact, with an additional €500 million in milestones and €2.9 billion in sales possible down the line.

So what does Merck do with bintrafusp alfa now? The therapy was once heralded as a future competitor to the mega-blockbuster Keytruda sold by U.S. competitor Merck & Co.

Merck KGaA said the company will use “advanced analytics” to comb through the vast data collected through the INTR@PID clinical program and better understand what happened—and how learnings can be applied to the field of immunotherapy.

The drug is a bifunctional immunotherapy designed to combine a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein. In plain English, bintrafusp alfa was supposed to control tumor growth by enhancing or restoring anti-tumor responses in the immune system. Merck and GSK hoped it could become a targeted treatment for difficult-to-treat cancers.

Merck and GSK had an expansive clinical program for bintrafusp alfa, including indications in non-small cell lung cancer, biliary tract cancer, cervical cancer, breast cancer and urothelial cancer.

https://www.fiercebiotech.com/biotech/merck-kgaa-gsk-cut-ties-bintrafusp-alfa-deal-had-4-2b-biobucks-line

Regeneron's Covid-19 antibody gets an in-patient boost

 Regeneron’s latest trial of its antibody cocktail Regen-Cov was intended to broaden the use of the treatment to patients hospitalised with Covid-19. And it looks to have succeeded, at least in some patients. In a phase 2/3 trial the combination of casirivimab and imdevimab met the primary endpoint of significantly reducing viral load within seven days of treatment. More importantly, it reduced the risk of death by 36% compared with placebo at day 29 for hospitalised Covid-19 patients not requiring high-flow oxygen or mechanical ventilation. However, this was not significant, as the trial was stopped early because of slow enrolment. And in an echo of the much larger Recovery trial, the greatest benefit was in seronegative patients – those who fail to mount an adequate response to infection – with the risk reduction here rising to 56%. Regen-Cov is not yet authorised for hospitalised patients, but the latest data could help support a nod here, at least in a seronegative population. This should give a much-needed option for in patients, but serostatus testing will have to become routine. 

https://www.evaluate.com/vantage/articles/news/snippets/regenerons-covid-19-antibody-gets-patient-boost

Editas falls well short of Brilliance

 Editas kept investors waiting for years for the first data from one of its Crispr-based gene editing projects. Yesterday, its big reveal disappointed.

The group claimed hints of efficacy with EDIT-101, which is being developed for the rare inherited eye disorder Leber congenital amaurosis, but these are hard to see. More troubling are reports of retinal tears and haemorrhage. Editas plans to push the dose of EDIT-101 higher, but the latest data suggest that finding a therapeutic window might be difficult.

Despite its positive spin on the results, which came from the phase 1/2 Brilliance trial, Editas’s stock sank 19% yesterday. But the company is still worth nearly $3bn, which seems hard to credit given its very early-stage pipeline.

Unmet need

True, there is an unmet need in Leber congenital amaurosis type 10 (LCA10), the disease subtype Editas is targeting, caused by mutations in the CEP290 gene. EDIT-101, which is injected subretinally, is designed to delete the mutation in question, c.2991+1655A>G, using Crispr-Cas9 in vivo gene editing.

The jury is still out on the effectiveness of this strategy. The results released yesterday came from two patients in the low-dose and three in the mid-dose cohort of Brilliance, testing 6x1011vg/ml and 1.1x1012vg/ml respectively.

According to Editas, two subjects in the mid-dose group showed signs of efficacy after three to six months of follow-up. For one of these patients that interpretation is debatable, given no improvement in best-corrected visual acuity with the EDIT-101-treated eye versus the patient’s untreated eye, which acted as a control.

For the best-performing patient, a 0.7logMAR improvement in BCVA versus control eye looks more clear-cut. The lead investigator of Brilliance, Dr Eric Pierce of the Massachusetts Eye and Ear hospital, noted during an Editas conference call yesterday that a 0.3logMAR improvement here was considered clinically meaningful.

However, this improvement was seen in only one patient out of five. Furthermore, Evercore ISI’s Liisa Bayko noted that in this subject BCVA had been measured using the Berkeley rudimentary visual test, which is not as well validated and reproducible as the more standard letter chart known as the early treatment diabetic retinopathy study.

Source: Compant presentation

It is difficult to conclude much about the efficacy of EDIT-101 on the available evidence. Perhaps things will become clearer next spring with longer-term results from the low and mid-dose cohorts, as well as data from the high-dose arm, testing 3x1012vg/ml. Editas is also starting a mid-dose paediatric cohort.

Toxicity might prove a stumbling block at a higher dose, though. Editas said in its press release and slides that no serious adverse events had been seen in Brilliance, highlighting a lack of treatment-related cataracts, oedema or retinal thinning.

However, a presentation yesterday at the International Symposium on Retinal Degeneration detailed one case of hypotony among two low-dose patients, and two retinal tears and one retinal haemorrhage among four mid-dose subjects.

Neutralising antibodies to AAV5, the viral vector used to deliver EDIT-101, were also seen in three patients, a fact omitted from Editas’s slide deck. When questioned about this on the conference call, company execs said that in patients who did have neutralising antibodies the levels were low.

Antisense contender

Perhaps patients would be willing to risk these adverse events with no other options available. But another LCA10 therapy is on the horizon: Proqr’s sepofarsen, an antisense project that binds to CEP290 RNA to enable correct splicing and production of the CEP290 protein. 

EDIT-101 might hold the promise of a once-and-done therapy, but sepofarsen is given every six months, still a relatively convenient schedule compared with some eye drugs.

And so far sepofarsen looks like a better bet, although patient numbers are admittedly small. In a phase 1/2 trial 11 sepofarsen-treated patients showed a 0.5.5logMAR improvement in BCVA.

Proqr is set to report data from the pivotal sham-controlled Illuminate trial next year, and all eyes will now be on this update.

https://www.evaluate.com/vantage/articles/news/trial-results/editas-falls-well-short-brilliance

AngioDynamics Reports Fiscal 2022 Q1 Results; Updates Guidance

 Fiscal 2022 First Quarter Highlights

• Net sales of $77.0 million increased 9.6% compared to the prior-year quarter

• Gross margin of 52.1% increased 120 basis points year over year

• GAAP loss per share of $0.18, and adjusted loss per share of $0.02

• The Company commenced a Limited Market Release of its AlphaVac Mechanical Thrombectomy device in September

Updating Fiscal Year 2022 Financial Guidance

The Company now expects its fiscal year 2022 net sales to be in the range of $310 to $315 million, an increase from its prior guidance of $305 to $310 million. The Company expects gross margin to be approximately 55.0% and adjusted earnings per share in the range of $0.00 to $0.05 as it continues to invest in new product launches to drive future growth.

Conference Call

The Company's management will host a conference call today at 8:00 a.m. ET to discuss its first quarter results.

To participate in the conference call, dial 1-877-407-0784 (domestic) or +1-201-689-8560 (international) and refer to the passcode 13723182.

This conference call will also be webcast and can be accessed from the "Investors" section of the AngioDynamics website at www.angiodynamics.com. The webcast replay of the call will be available at the same site approximately one hour after the end of the call.

A recording of the call will also be available from 11:00 a.m. ET on Thursday, September 30, 2021, until 11:59 p.m. ET on Thursday, October 7, 2021. To hear this recording, dial 1-844-512-2921 (domestic) or +1-412-317-6671 (international) and enter the passcode 13723182.

https://finance.yahoo.com/news/angiodynamics-reports-fiscal-2022-first-110000246.html

Alzamend Neuro: Positive Pre-IND FDA Response for Alzheimer's Candidate

 FDA Agrees to Alzamend’s Plan to Conduct a Combined Phase 1 and 2 Clinical Trial for AL002

Alzamend Neuro, Inc. (Nasdaq: ALZN) ("Alzamend"), an early clinical-stage biopharmaceutical company focused on developing novel products for the treatment of neurodegenerative diseases and psychiatric disorders, today announced that it has received a written response to its meeting request relating to its Type B Pre‑Investigational New Drug ("IND") application from the U.S. Food and Drug Administration (the "FDA") providing a path for Alzamend’s planned clinical development of AL002. AL002 is a patented method using a mutant-peptide sensitized cell as a cell-based therapeutic vaccine that seeks to restore the ability of a patient’s immunological system to combat Alzheimer’s.

Based on the FDA’s written feedback, Alzamend anticipates filing the IND by the end of November 2021 and initiating the clinical trial of AL002 in the first quarter of 2022.

https://finance.yahoo.com/news/alzamend-neuro-receives-positive-pre-141100659.html