New COVID-19 mutations putting a strain on trial resumptions

 The new strains of COVID-19 that are more transmissible and potentially able to dampen vaccine efforts are causing clinical trial resumptions to slow.

This is according to life science analytics firm GlobalData, which found that while many studies were on their way to restarting as the global peak started to decline last year, the recent surge in cases in the West—predominately due to new, more transmissible strains first seen in the U.K., Brazil and South Africa—has “led to increased restrictive measures and has slowed down the resumption of disrupted clinical trials."

As of Jan. 25, GlobalData found that 929 disrupted trials have resumed and, out of these, 71.9% are currently recruiting participants, 12.8% have completed recruitment but are still ongoing and 0.5% of trials have yet to start recruiting subjects.

“There is a slight, steady increase of trials resuming activity, with the initial general trend showing a gradual increase in the overall percentage of trials for each trial status,” said Priya Nair, a trials intelligence analyst at GlobalData.

“However, between December 23 and January 25, ongoing recruiting trials decreased from 74.6% to 71.9%, and completed trials increased from 10.6% to 12.8%. The majority of trial disruptions can be attributed to patient safety measures, strict lockdown requirements, social distancing procedures and the high demand on medical professionals to treat COVID-19 patients.”

Geographically, the U.S. has the highest number of resumed trials at 87.5%, followed by the U.K. at 10.8% (which has issued national lockdowns since December amid its new strain), Spain at 9%, France at 8.8% and Germany at 8.1%.

Nair said here was hope on the horizon in the form of  Pfizer-BioNTech, University of Oxford-AstraZeneca and Moderna’s vaccines, which could help decrease cases, hospitalizations and deaths in the coming months. “If this occurs, then the potential of disrupted trials resuming could be likely.”

Nair added, though, this will also depend on how well the shots work against the new variants, some of which may be partially resistant to the effects of the current crop of vaccines. 

https://www.fiercebiotech.com/cro/new-covid-mutations-putting-a-strain-trial-resumptions-report

Covid-19 could scupper Glaxo’s next vaccine push

 Developing vaccines for respiratory syncytial virus has been tough at the best of times. But now is an expecially poor moment to be testing vaccines – aside from those for Covid-19 – given that social-distancing measures are impeding the spread of other infections. These worries have not stopped Glaxosmithkline, which today said it was pushing its second RSV vaccine candidate, GSK3844766A, into phase III. The project is being tested in old adults who, along with infants, are at the biggest risk from RSV. During a fourth-quarter earnings call Glaxo execs brushed off concerns that Covid-19 lockdowns might hurt the trial’s chances, noting that by the first six to nine months of this year most old adults should have received a Covid-19 vaccine. Whether this will lead to more social mixing – and, crucially for Glaxo, more RSV transmission – is the big unknown. Glaxo needs to succeed here: it counts its adult and maternal RSV projects among 10 potential blockbusters slated for launch by 2026. And the net present value of Glaxo’s RSV projects, according to Evaluate Omnium, is $1.7bn. Given what is at stake, perhaps the group might have been better off waiting for social-distancing measures to ease before pressing on.

GSK's respiratory syncytial virus vaccine push
Project	Setting	Vaccine type	Status	Trial details
GSK3888550A	Maternal	Recombinant protein	Ph3	Grace (NCT04605159), interim data H2 2022
GSK3844766A	Adults >60 years old	Recombinant protein, adjuvanted	Ph3	Aresvi 004 (NCT04732871), interim data H2 2022; Aresvi 006 to start in coming months
GSK3389245A	Paediatric	Recombinant chimpanzee adenoviral vector	Ph2	Ph1/2 in sero-naive infants (NCT03636906); ph2 in sero-positive infants (NCT02927873)
Source: EvaluatePharma, clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/snippets/covid-19-could-scupper-glaxos-next-vaccine-push

Bluebird split looks premature

 Bluebird's self-styled “chief bluebird”, Nick Leschly, insisted today that his company’s split into separate gene therapy and oncology businesses was still on track, but a safety scare with the lead asset, Lentiglobin, suggests that a rethink might be needed.

Assuming a worst-case scenario, without Lentiglobin the remaining gene therapy entity is left with little to attract investors' attention. The question has to be asked whether it is a wise move to press ahead now with the oncology spin-out, however attractive that tax-free plan might seem to those hoping for an acquisition.

Of course, Bluebird might still be able to avoid that worst-case scenario. A causal link has not yet been proven between Lentiglobin and the two cases of cancer – acute myeloid leukaemia and myelodysplastic syndrome – that were revealed today. Both occurred in the HGB-206 phase I/II trial in sickle cell disease, and Bluebird has now halted this trial, as well as its phase III sickle cell study, HGB-210.

The group has also suspended sales of Lentiglobin for beta-thalassaemia in Europe, where the therapy is branded Zynteglo, although Mr Leschly stressed that no cases of AML or MDS had been reported in this population.

Bluebird lost about $1bn in market cap this morning.

It probably does not help that the company has been here before. In December 2018 a separate case of MDS was reported in the HGB-206 trial; at the time Bluebird blamed the busulfan preconditioning regimen used before therapy to damp down patients’ immune systems.  

Insertional mutagenesis?

The big worry with the new cases is that Lentiglobin, an ex vivo gene therapy that employs a lentiviral vector, has led to insertional mutagenesis, namely that the vector-delivered gene has tampered with a target cell's chromosomal arrangement and in effect triggered a cancerous phenotype.

Regarding the case of AML, which occurred more than five years after dosing with Lentiglobin, there is a worrying sign: during a conference call today Mr Leschly said vector had been detected in the patient’s tumour cells. However, it is still unclear whether the vector is merely a “passenger” here or if it helped drive the oncogenic mutations.

To figure this out Bluebird will now investigate whether the vector was inserted near to genes involved in oncogenesis or genome stability and, if so, whether there was any upregulation of those genes.

For the case of MDS, the company has not yet ascertained whether the tumour cells are carrying the vector. However, the signs here are more promising from Bluebird’s perspective: this patient had a genetic abnormality, trisomy 8, seen in 10-15% of MDS cases, suggesting that underlying risk factors might have contributed. And the timeframe looks better for the company, with the diagnosis being made around six months after Lentiglobin dosing.

Mr Leschly stressed that sickle cell disease itself could cause blood cancers, given the stress that it puts on patients’ bone marrow.

Bluebird also said busulfan could be to blame for the latest cancer cases. But the group’s chief scientific officer, Philip Gregory, conceded that it would be hard to unpick whether preconditioning was the cause versus an underlying mutation.

The company’s investigation should take weeks, rather than months, Mr Leschly said. If the vector is indeed at fault this would be bad news for the bulk of Bluebird’s genetic disease pipeline, including Lenti-D, as well as for other gene therapy players evaluating lentivirus-based approaches.

For now Bluebird has its oncology pipeline to fall back on. Unless the worst case for Lentiglobin can be ruled out conclusively Bluebird needs to hold on to this business.

Splitting the difference: Bluebird's planned separation
Project	Description	Status
Oncology newco…
Ide-cel (bb2121)	Anti-BCMA Car-T therapy for multiple myeloma	Filed (delayed Mar 27, 2021 Pdufa date)
bb21217	Anti-BCMA Car-T therapy for multiple myeloma	Ph1/2
MCC1 TCR	Anti-MCC1 engineered TCR for Merkel cell carcinoma	Ph1/2
bbT369	Anti-CD79a & CD20 dual Car-T therapy for NHL	Preclinical
DARIC33	Rapamycin-regulated anti-CD33 Car-T therapy for AML	Preclinical
Mage-A4 TCR	Anti-Mage A4 engineered TCR for solid tumours	Preclinical
…and what Bluebird is left with
Beti-cel (Lentiglobin)	Lentiviral β-globin gene therapy for beta-thalassaemia & sickle cell disease	Approved in EU for beta-thal as Zynteglo; ph3 for SCD
Eli-cel (Lenti-D)	Lentiviral ABCD1 gene therapy for cerebral adrenoleukodystrophy	Ph3
BCL11A shRNA	Short-hairpin microRNA for sickle cell disease	Ph1
Source: company filings. https://www.evaluate.com/vantage/articles/news/trial-results/bluebird-split-looks-premature

FDA accepts Sesen Bio filing for approval of Vicineum in treating bladder cancer

 Shares of Sesen Bio (NASDAQ:SESN) were 10.2% higher as of 11:48 a.m. EST on Tuesday. The big jump came after the company announced that the Food and Drug Administration accepted its Biologics License Application (BLA) filing for Vicineum in treating bladder cancer. The FDA also granted Priority Review status for the application.

Acceptance of the BLA for Vicineum clears one more hurdle toward Sesen's lead candidate winning FDA approval. The agency also said that it doesn't plan to convene an advisory committee to review the BLA for Vicineum. That removes yet another potential hurdle.

The biggest news for the biotech, though, was the FDA's decision to grant it Priority Review status. Normally, it takes 10 months from acceptance of a regulatory filing for the FDA to make an approval decision for a new drug. But Priority Review shortens the period to six months. Sesen expects the FDA will announce its approval decision for Vicineum by Aug. 18.

CEO Thomas Cannell said that the company has "reached an inflection point" with the FDA decisions announced today. The BLA acceptance, the decision to not require an advisory committee meeting, and the granting of Priority Review status appear to put Sesen on track to shift from being a clinical-stage biotech to a commercial-stage biotech.

FDA approval of Vicineum this summer could be a huge catalyst for the biotech stock. But it's also possible that Sesen's shares could receive a bump sooner than that. The company anticipates submission of its European regulatory filing for Vicineum within the next one to two months. 

https://www.fool.com/investing/2021/02/16/why-sesen-bio-stock-is-soaring-today/

Exact Sciences (EXAS) to Acquire Ashion

 Exact Sciences Corp. (Nasdaq: EXAS) today announced that it has entered into an agreement to acquire Ashion Analytics, LLC (Ashion) from The Translational Genomics Research Institute (TGen), an affiliate of City of Hope. Ashion is a CLIA-certified and CAP-accredited sequencing lab based in Phoenix, Arizona with the genomics testing capabilities necessary to address the increasingly complex needs of clinical, academic, and biopharma customers focused on precision cancer treatments. The team at Ashion will help accelerate the development of Exact Sciences' precision oncology portfolio, including minimal residual disease (MRD) and other sequencing-based tests.

This acquisition will build upon the recent license of the TARDIS technology from TGen and strengthen the relationship between the institutions through a planned 10-year research collaboration. TARDIS is a highly sensitive, patient-specific liquid biopsy-based test that can detect small amounts of tumor DNA in blood for use in MRD testing.

Exact Sciences continues to strengthen the robust foundation established for Oncotype to lead precision oncology," said Kevin Conroy, chairman and CEO of Exact Sciences. "We're excited to work with Ashion to bring the TARDIS technology to patients faster and continue to develop advancements in MRD testing. We're thrilled to collaborate with TGen and City of Hope, complementing our relationships with other world-renowned cancer research leaders including Mayo Clinic and Johns Hopkins University."

Ashion leverages the genetic information from a patient's tumor and normal genomes to provide industry-leading oncology solutions. Ashion developed GEM ExTra®, one of the most comprehensive genomic cancer tests available, and provides access to whole exome, matched germline, and transcriptome sequencing capabilities. The team at Ashion will be instrumental in incorporating the TARDIS technology into Exact Sciences' MRD test development.

Under the agreement, Exact Sciences would also enter a 10-year collaboration, bringing in the expertise of TGen and City of Hope, to develop differentiated MRD testing capabilities for patients and establish the clinical evidence necessary to drive adoption.

https://www.streetinsider.com/Corporate+News/Exact+Sciences+%28EXAS%29+to+Acquire+Ashion/17981504.html

Tenet, Providence, other health giants band together to form new health data startup

 Some of the biggest names in healthcare including Tenet Health, Providence and CommonSpirit Health have launched a new startup to pool and analyze patient data for research and drug development.

Capitalizing on health systems' troves of patient data, 14 health systems are backing the new company, called Truveta. Among the backers are AdventHealth, Advocate Aurora Health, Baptist Health of Northeast Florida, Bon Secours Mercy Health, Hawaii Pacific Health, Henry Ford Health System, Memorial Hermann Health System, Northwell Health, Novant Health, Sentara Healthcare and Trinity Health.

The Seattle-based startup will pull together and sell normalized and de-identified data from the group of providers with a keen eye on protecting patient privacy and security, the companies said in a press release.

The new data platform, using the power of artificial intelligence and machine learning, will help deliver "personalized medicine, advance health equity, and empower the health community with insights on how to best treat patients," the press release said.

The 14 health systems represent tens of millions of patients and operate thousands of care facilities across 40 states. 

Truveta will be jointly owned by the hospital operators and will be board-advised with a strong focus on ethics and health equity, data integrity and clinical outcomes.

Former Microsoft executive Terry Myerson will lead the new startup.

Myerson told The Wall Street Journal that the company is still developing its pricing plans. Potentially, fees will vary depending on the type of entity seeking access, the WSJ reported.

“The COVID-19 pandemic has shown us how much the world needs to learn faster, so we can better serve our communities,” Myerson said in a statement. “Our vision is to save lives with data. We want to help researchers find cures faster, empower every clinician to be an expert, and help families make the most informed decisions on their care. We believe the Truveta platform can help improve health equity and advance personalized medicine. We are honored to be partnering with innovative and world-class health providers in this pursuit.”

“For years we have seen the opportunity for diverse health providers to come together with a shared sense of purpose and use our collective data for the common good of humanity. With Truveta, we created a unique model that is led by the health providers yet supported by one of the most talented technical teams to focus on health,” said Rod Hochman, M.D, president and CEO of Providence, in a statement.

Hochman said the hospital systems will focus on research questions around health equity as well as improving medical treatment, the WSJ reported.

The COVID-19 pandemic illustrates how quickly healthcare must move to effectively serve patients, according to the companies. The healthcare community has made remarkable progress, from diagnosis to vaccine distribution in less than a year.

Truveta’s innovative health provider partners agree COVID-19 must be a catalyst for even more rapid progress, the companies said in the press release.

Truveta aims to drive innovation in patient care and the development of new therapies through the creation of a data platform researchers can use to analyze billions of clinical data points with a single search.

The Truveta platform will structure and normalize a wide range of data across structured and unstructured data types to unlock the power of de-identified data across all diagnoses, geographies and demographics. Using advanced AI and machine learning, Truveta will deliver continuous learning to physicians, researchers, biopharma and more with aggregate analysis of conditions, therapies and prognoses, according to the press release.

Health system leaders involved in the effort said protecting patient data privacy would be a key priority for Truveta.

“We know health data is unlike other data. It is the very definition of personal,” Myerson said. “While we embark on our pursuit to generate knowledge and insights to improve patientcare around the world, we must do so with the utmost caution to protect the privacy of patients.”

The initiative is an important step in unlocking the hidden insights from data sitting in silos in large health systems, said Paddy Padmanabhan, founder and CEO of Damo Consulting, a growth strategy and digital transformation advisory firm.
 
“Healthcare has been hobbled by the inability to harness available data to improve healthcare outcomes, enhance patient experiences and reduce health inequities," he said.
 
Truveta's success will depend on execution, he added.

“Where will the data be hosted? How will Truveta build the advanced analytics and AI capabilities required to turn the vision to reality?" he said. “Truveta is a welcome new approach to industry-level collaboration for turning data into insights. However, the fact is that it is a collaborative effort among health systems and the data sets therefore provide only a partial view of patient histories for driving innovations in care management and developing new therapies."

Over the longer term, the industry will need to achieve active collaboration across health plans and life sciences companies as well to unleash innovation in new therapies, drive research and improve healthcare outcomes, Padmanabhan said.

https://www.fiercehealthcare.com/tech/tenet-providence-other-health-giants-band-together-to-form-new-health-data-startup

Citi Downgrades Unity Biotechnology

 To Sell

https://www.streetinsider.com/Analyst+PT+Change/Citi+Downgrades+Unity+Biotechnology+Inc+%28UBX%29+to+Sell/17971693.html