Novavax Inc said on Friday its COVID-19 vaccine candidate showed immune response and protection against the SARS-CoV-2 Beta variant, which was originally identified in South Africa, in three animal and human studies.
Friday, June 11, 2021
Ocugen gets a black eye as FDA denies emergency OK for COVID jab
Ocugen is the first company to be affected by the FDA’s recent decision to raise the bar on emergency use authorisations for COVID-19 medicines, and will have to file for full approval of its vaccine candidate.
That will hold back the biotech’s Covaxin shot by several months, and the delay put pressure on Ocugen’s share price, which fell more than 25% after the announcement.
The Philadelphia-based company said it had taken the decision to go down the biologics license application (BLA) route for Covaxin based on FDA feedback to the EUA data package it had submitted to the agency.
Ocugen added that it is now “in discussions with the FDA to understand the additional information required to support a BLA submission,” but will likely have to carry out an additional clinical trial.
The FDA’s Centre for Biologics Evaluation and Research (CBER) updated its guidance on EUAs for COVID-19 vaccines last month, which indicated it may decline future requests.
It’s a big disappointment for the specialist in drugs and gene therapies for ocular diseases, although the decision to embark on a COVID-19 programme has been viewed as a somewhat maverick move for the biotech.
Ocugen acquired US co-development rights to Covaxin in February from Indian pharma company Bharat Biotech, which already has emergency approval in India for the vaccine, which is based on inactivated SARS-CoV-2 virus.
Under the terms of that deal, Bharat is responsible for initial supplies of the shot, while Ocugen ramped up its own manufacturing capacity.
“While this will extend our timelines, we are committed to bringing Covaxin to the US,” insisted Ocugen chief executive Shankar Musunuri.
“This differentiated vaccine is a critical tool to include in our national arsenal given its potential to address the SARS-CoV-2 variants,” he added.
That includes the more transmissible B.1.617.2 or delta variant of SARS-CoV-2 – to use the World Health Organisation’s new naming system, according to Musunuri. Bharat has also reported data suggesting the shot is effective against the beta (B.1.351) variant.
Covaxin and AstraZeneca’s vaccine – sold as Covishield in India and produced there by the Serum Institute of India under license – have formed the backbone of India’s COVID-19 vaccination drive. The Russian Sputnik V vaccine was approved for use in India in April.
Covaxin has come under scrutiny in India for its relatively high price compared to the other available vaccines, as well as questions about the speed of its approval in India. It was given the go-ahead in January, well before Bharat reported phase 3 data suggesting a protective efficacy of 78%.
Ocugen’s acting chief medical officer Bruce Forrest said that clinical trials of Covaxin are “supportive of it being generally well tolerated with a good safety profile, with…India reporting no potential thromboembolic events following the administration of over 6.7 million doses.”
Covaxin is already approved or emergency use in 13 countries, with applications in pending in 60 more, including in Canada.
https://pharmaphorum.com/news/ocugen-gets-a-black-eye-as-fda-denies-emergency-ok-for-covid-jab/
Vertex clears the way for Arrowhead
Vertex’s admission that its second try in the rare respiratory disease alpha-1 antitrypsin deficiency has failed will embolden Arrowhead, whose RNAi therapeutic will now have a clear shot at becoming the first therapy to treat the underlying cause of this condition.
It will come as cold comfort that the phase 2 study of the Vertex project, VX-864, toplined yesterday, actually hit its primary endpoint, showing a statistically significant increase in functional alpha-1 antitrypsin (AAT) levels versus placebo. But, to Vertex’s credit, the group admitted that the result fell short of clinical relevance, and VX-864 will now be shelved.
Investors' eyes now turn to Arrowhead’s Takeda-partnered ARO-AAT, a project using RNAi to knock down the liver’s production of mutant AAT and prevent build-up of this protein in the liver, the cause of liver and lung disease.
Arrowhead reported positive 24-week liver biopsy results last September, and now a key catalyst awaits: the full dataset of 12-month biopsies is due to be unveiled at a late-breaking presentation at Easl on June 26.
Dud
One thing seems certain, however, and this is that Vertex’s latest approach using small-molecule correctors to fix the misfolding of AAT is a dud. VX-864 is now headed for the scrapheap, where it will join VX-814, a structurally distinct project that failed last year. Though, after VX-814, few had expected VX-864 to work, Vertex still opened down 9% this morning.
Vertex said in its phase 2 study VX-864 yielded mean plasma levels of functional AAT of 6.2μM at 28 days. This amounted to a roughly 2.2μM increase from baseline, which compared against the 0.1μM decline seen in placebo recipients was statistically significant for each of three 100-500mg doses (p<0.0001).
However, the absolute 6.2μM number fell well short of the threshold for clinical relevance, which Vertex had set at 11.0μM. Moreover, there was no dose response, with all three doses yielding roughly the same pattern of functional AAT production across the 28 days.
Source: company presentation.
The study had recruited patients with the PiZZ genotype, meaning that they were genetically homozygous and thus had severe disease, being unable to transport AAT from the liver to the lungs.
While the VX-864 data are overall negative, they are by no means a disaster for Vertex’s plan to become an AAT deficiency player; the company is showing that its small-molecule correctors are mechanistically doing what they are supposed to, albeit not strongly enough.
An important point is that VX-864 yielded no discontinuations due to side effects, and no serious toxicities. With VX-814 the company could not even find a therapeutic window, and the project was brought down partly by liver toxicity; yesterday Vertex stressed that liver function tests were similar between placebo and VX-864 cohorts.
And the company is not giving up. Its next iteration of AAT correctors is set to enter clinical testing next year.
https://www.evaluate.com/vantage/articles/news/trial-results/vertex-clears-way-arrowhead
Health tech Spac deals on pause
The number of health technology groups listing by merging with special purpose acquisition companies has slowed dramatically from the start of the year. But the closing of two such deals this week shows that there is still some action to be found.
The companies involved are active in sectors that have seen a lot of attention from Spacs: telemedicine and proteomic analysis. But the slowdown in deal making, which appears to be partly a result of a possible move by the SEC to change the way it classifies Spac warrants, is clear.
In the first quarter of 2021 nine Spac acquisitions of health tech companies were announced; in the second quarter there were just five, and three of these came in the first half of April. There has also been a sharp drop in the number of healthcare-focused Spacs floating.
An Evaluate Vantage analysis of data provided by the website SpacInsider shows that this figure has shrunk from a peak of 15 in January to just one last month. The amount of money they have drummed up has also declined sharply. The analysis below covers biopharma companies as well as health technology groups.
Count: 11
One likely reason for the diminished activity – and the dates certainly line up – is a statement made by the SEC on April 12. The regulator said it was concerned about the accounting of Spac warrants, and suggested that it might start to classify these as a liability on the balance sheet rather than as equity. Since then many Spacs appear to have focused on getting their filings in order rather than progressing deals.
Quantum leap
Still, there are exceptions. Yesterday’s finalising of the deal between the proteomics specialist Quantum-Si and Highcape Capital Acquisition Corp creates a sizeable new player in the nascent field of proteomics. The deal confers on Quantum-Si a pro forma equity value of $1.5bn, a chunky amount for a group whose technology will not reach market until next year – and even then, only for research use.
The valuation includes the $109m of cash held in Highcape’s trust account that will be transferred to Quantum-Si, as well as a $425m Pipe round, in which Foresite Capital Management, Eldridge, accounts advised by ARK Invest and Glenview Capital Management participated.
Part of the reason for Quantum-Si’s success is its founder. Dr Jonathan Rothberg has founded and either floated or sold several medtech and diagnostics groups, notably Curagen, Raindance and Ion Torrent. More recently he established the handheld ultrasound device developer Butterfly Network, which went public via a Spac deal in February.
Quantum-Si’s tech is designed for the digital analysis of proteins and is initially aimed at academic research and drug discovery, markets it claims are worth a collective $21bn. Following that it has ambitions to develop diagnostic applications in healthcare.
Speaking the right language
This week’s other Spac deal was perhaps slightly more unusual in that the acquirer bought two medtechs simultaneously. Gigcapital2 closed its acquisitions of the telemedicine groups Uphealth and Cloudbreak Health, with Uphealth giving its name to the new entity.
Uphealth offers telemedicine services such as video appointments with doctors, as well as a digital pharmacy including a compounding laboratory, enabling patients to order their prescriptions online. Cloudbreak’s speciality is incorporating medical interpreters into video calls, with the company claiming that this allows healthcare professionals to provide care in over 250 languages.
Of these two groups, Quantum-Si is the winner in terms of shareholder enthusiasm, though neither has exactly set the markets alight. Quantum’s stock is up 2% since its Spac merger was announced, whereas Uphealth’s is 3% down.
https://www.evaluate.com/vantage/articles/news/deals/health-tech-spac-deals-pause
Adamis updates on trial startup for Tempol for Covid-19
Adamis Pharmaceuticals Corporation (NASDAQ: ADMP) today announced that clinical trial start-up activities are underway for examining the effects of Tempol, which is the Company’s experimental drug, in the treatment of COVID-19. Adamis is carrying out these activities with a large clinical research organization (CRO).
Commenced activities include site identification and initiation, data base production, vendor management, and the establishment of an independent data safety monitoring board of infectious disease experts, who will review the safety and efficacy of the trial. Clinical trial drug product and placebo have also been obtained.
The goal of the trial — entitled “A Phase 2/3, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study to Examine the Effects of Tempol (MBM-02) on Preventing COVID-19 Related Hospitalization in Subjects with COVID-19 Infection” – is to examine the safety and activity of Tempol in COVID-19 patients early in the infection. In addition to safety, the study will examine markers of inflammation, symptoms, and the rate of hospitalization for patients taking Tempol versus placebo. Additional information about the trial can be found on www.clinicaltrials.gov using the identifier NCT04729595.
The clinical trial start-up activities follow recently published work by the National Institutes of Health (NIH), which has identified Tempol as a potentially potent antiviral for COVID-19. As previously reported, in a study of cell cultures conducted by NIH researchers, Tempol demonstrated an ability to limit SARS-CoV-2 infection by impairing the activity of a viral enzyme known as RNA replicase. Tempol produced a 5 log decrease in virus levels in cells infected with SARS-CoV-2. Notably, as a single agent, Tempol performed better in inhibiting RNA replicase than Remdesivir®, which has been approved on an emergency use basis for the treatment of COVID-19. Tempol also synergized with Remdesivir®.
Moderna, Tabuk Partner to Commercialize Moderna’s COVID-19 Vaccine in Saudi Arabia
-Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, and Tabuk Pharmaceutical Manufacturing Company (a fully owned subsidiary of Astra Industrial Group), a leading Saudi pharmaceuticals company, today announced an agreement to commercialize the Moderna COVID-19 Vaccine and future variant-specific booster candidates in Saudi Arabia.
Under the terms of this agreement, Tabuk Pharmaceuticals will hold the marketing authorization for the Moderna COVID-19 vaccine in Saudi Arabia. Beyond the Moderna COVID-19 Vaccine and Moderna’s updated variant booster candidates, the agreement also gives Tabuk the possibility to discuss opportunities to distribute other Moderna mRNA products if authorized in the future.
Aptose sinks after corporate update event
Aptose Biosciences Inc. (“Aptose” or the “Company”) (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated therapeutics that target the underlying mechanisms of cancer, is releasing highlights from a corporate update event being held today, Friday, June 11, 2021, at 8:00 a.m. ET, in concurrence with participation at the EHA2021 Virtual Congress (EHA). The event is focused on the current clinical status of luxeptinib, Aptose’s oral, first-in-class FLT3 and BTK kinase inhibitor currently in two Phase 1 a/b trials, one trial in patients with relapsed or refractory acute myeloid leukemia (AML), and the other trial in patients with relapsed or refractory B cell malignancies. The live and archived webcast of the presentation is available on Aptose’s website here.
“Our recent clinical experience has confirmed that luxeptinib is an active drug in several indications across both myeloid and lymphoid malignancies, which is consistent with our hypotheses from our broad portfolio of preclinical work,” said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. “We are especially encouraged to see this anti-tumor activity -- including meaningful blast reductions -- emerging even in heavily pretreated and clinically challenging patients, and we now look forward to continuing dosing at higher exposures for longer periods in order to explore fully the potential of this singular drug.”
Aptose’s presentation provides a recap on luxeptinib, including the following key highlights:
Luxeptinib clinical program in AML
In the ongoing Phase 1a/b study in patients with relapsed or refractory AML, we completed the first two dose cohorts (450mg and 600mg) and have escalated to the third cohort (750mg). We plan to dose escalate further and have observed no safety trends likely to prevent continued escalation.
We achieved anticipated steady state PK levels and PD inhibition of target kinases, in line with our parallel study in different patient populations.
The first two dose cohorts delivered encouraging anti-leukemic activity in multiple patients, including a durable MRD-negative complete response in a FLT3-ITD AML patient who had relapsed after two allogeneic stem cell transplants, multiple lines of chemotherapy, and prior FLT3 inhibitor therapy.
Based on the totality of our preclinical and clinical observations to date, we expect to select an expansion dose and expansion cohort strategy for AML during 2H21 and aim to explore select disease genotypes under monotherapy and combination therapy programs.
Luxeptinib clinical program in B-cell malignancies
In the ongoing Phase 1a/b study in B-cell malignancies, intermediate dose levels to date have delivered all leading indicators of clinical activity, including target engagement with dose-dependent inhibition of phospho-BTK, treatment-related lymphocytosis in patients presenting with classic CLL, and tumor reductions across different B-cell malignancies (FL, CLL, SLL, WM).
We continue to observe cases of clear reversal of aggressively growing disease upon intra-patient dose-escalation and longer times on drug, suggesting that even aggressive disease may be successfully challenged with higher exposure levels and extended dosing duration of luxeptinib.
We currently are treating patients at 750mg BID, and we plan to continue further escalation to higher dose levels and for extended duration to tackle an increasingly treatment refractory presenting population.
We plan to continue exploring the spectrum of B-cell malignancies in line with the preliminary anti-tumor activity observed in the study to date.
In addition, clinical data for luxeptinib and APTO-253 were presented at EHA this morning. The APTO-253 poster presentation contained a full update of the clinical status of APTO-253, a first-in-class small molecule MYC inhibitor in a Phase 1a/b trial in patients with relapsed or refractory AML or high-risk myelodysplastic syndrome (MDS). The posters are now available on the presentations page of Aptose’s website here.
Key highlights from the APTO-253 poster:
In the ongoing Phase 1a/b study in patients with relapsed or refractory AML and high-risk MDS, APTO-253 has been well-tolerated in the patients treated at 20, 40, 66, 100 and 150 mg/m2 over multiple cycles.
In the peripheral blood of patients, APTO-253 monomer rapidly transforms to and co-exists with the mechanistically active Fe(253)3 conjugate, and the serum levels of APTO-253 and the Fe(253)3 conjugate are dose proportional with significantly higher concentrations of Fe(253)3 conjugate that are sustained for longer periods of time compared to monomer, suggesting that further dose escalations may provide more sustained pressure on the MYC target gene and alter the biology of the tumor cells.
Collectively, the findings from the ongoing Phase 1a/b study support continued dose escalation of APTO-253. The study is current enrolling patients with AML and MDS at the sixth dose level of 210 mg/m2, and subsequent dose escalations are anticipated.
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