Biocryst joins the push against Soliris

 Full data on Biocryst’s oral factor D inhibitor BCX9930 are good enough to warrant a push into phase III. The longer-term question here is how the company will compete in a crowded space against much larger rivals. Mid-stage data in the rare severe anaemia paroxysmal nocturnal haemoglobinuria are encouraging, showing BCX9930 to improve patients’ blood biomarkers and prevent the transfusions on which many sufferers rely. The small study recruited treatment-naive subjects and those non-responsive to Alexion’s Soliris. In the former group haemoglobin levels were returned to close to normal and transfusions reduced to zero once patients were on higher doses of ‘9930. Haemoglobin also reached almost normal levels in the latter, harder-to-treat group, and although one patient required a transfusion the results are not hugely different from phase II data generated with experimental projects from Novartis and Alexion/Astrazeneca. Roche and Apellis are also taking aim at PNH, and pivotal data from all of these projects are needed to make more rigorous comparisons. All are trying to improve on the hugely successful Soliris with more convenient agents, but it is worth remembering that Alexion managed to build a blockbuster franchise by being the only option available.

Cross trial comparison of mid-stage trials in PNH patients inadequately controlled on Soliris or Ultomiris
	Iptacopan	Danicopan	BCX9930
Company	Novartis	Alexion/Astrazeneca	Biocryst
Mechanism	factor B inhibitor	factor D inhibitor	factor D inhibitor
Study*	NCT03439839	NCT03472885	NCT04330534
Number of patients	10	11	6
Baseline haemoglobin	not given	mean 7.9g/dl	mean 8.9g/dl
Increase from baseline	mean 2.9g/dl	mean 2.4g/dl	mean 3.2g/dl
End of study haemoglobin	>12g/dl in 8 of 10**	mean 10.3g/dl***	mean 12.2g/dl****
Transfusion avoidance?	At mean 241 days on treatment, no transfusions	95.8% reduction (one transfusion during 24 week trial)	5/6 remained transfusion free (83%)
Note: *all given in combination with Soliris; **at week 13; ***at week 24, ****median 13 weeks on therapeutic dose. Source: company presentations.

 

Chasing Soliris: the crowded late-stage PNH pipeline
Project	Description	Company	Note
APL-2 (pegcetacoplan)	Subcutaneous C3 inhibitor	Apellis	Pegasus trial in treatment-experienced patients succeeded, Pdufa May 14; Prince trial in naïve due to read out H1 2021
Iptacopan	Oral factor B inhibitor	Novartis	Two pivotal trials under way in treatment-experienced and naive; results due from 2022
Danicopan (ALXN2040)	Oral factor D inhibitor	Alexion/Astrazeneca	Phase III under way as add-on to Soliris; results due late 2022
Crovalimab	Subcutaneous C5 inhibitor	Roche	Three pivotal trials listed in treatment-experienced, naïve and H2H vs Soliris; results due late 2022/23
BCX9930	Oral factor D inhibitor	Biocryst	Phase III trial due to start H2 2021
And don't forget the Soliris biosimilars…
ABP 959	Intravenous C5 inhibitor	Amgen	Phase III under way
BCD-148	Intravenous C5 inhibitor	Biocad	Phase III under way
SB12	Intravenous C5 inhibitor	Samsung Bioepis	Phase III under way
Source: EvaluatePharma & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/snippets/biocryst-joins-push-against-soliris

AstraZeneca to publish full trial data after U.S. rebuke

 

AstraZeneca will publish up-to-date results from its latest COVID-19 vaccine trial within 48 hours after U.S. health officials said the drugmaker's analysis of the shot's efficacy may not have been based on all the available data.

The rare public rebuke marks the latest setback for the vaccine which was hailed as a milestone in the fight against the COVID-19 pandemic but has since been dogged by questions over its effectiveness and possible side effects.

AstraZeneca said results it published on Monday giving the shot an efficacy rate of 79% were based on an interim analysis of data through Feb. 17 and it would now "immediately engage" with the panel monitoring the trial to share its full analysis.

The Anglo-Swedish drugmaker said on Tuesday it had reviewed the preliminary assessment of its full, or primary, analysis and found it to be consistent with the interim report.

Its shares were down 2.5% in London trading.

The U.S. National Institute for Allergy and Infectious Diseases (NIAID) said on Monday that the board charged with ensuring the trial's accuracy had expressed concern the company may have given an incomplete view of the shot's effectiveness.

Anthony Fauci, director of the NIAID, said the whole issue was a really unfortunate unforced error.

"This is very likely a very good vaccine and this kind of thing does ... nothing but really cast some doubt about the vaccines and may contribute to the hesitancy," he told "Good Morning America" on ABC News.

"The data really are quite good but when they put it into the press release it wasn't completely accurate," he said. "We have to keep essentially trying as hard as we can to get people to understand that there are safeguards in place."

'NEGATIVE REPORTS'

Besides being 79% effective in stopping symptomatic illness in the trial in the United States, Chile and Peru, the data also showed the shot was 100% effective against severe or critical forms of the disease and posed no increased risk of blood clots.

The new doubts about the shot's efficacy, however, coincide with its rollout in dozens of countries and clouds the timeline for its emergency use authorization in the United States.

"This is indeed an extraordinary act. The negative reports about this vaccine do not stop, although my assessment is that it is well tolerated and safe, but clearly less effective than the two mRNA vaccines," Peter Kremsner, from the University Hospital in Tuebingen, Germany.

Rival vaccines from Pfizer/BioNTech and Moderna that use so-called mRNA technology produced efficacy rates of about 95% each, far above the 50% benchmark set by global regulators.

The panel monitoring the AstraZeneca trial, the Data and Safety Monitoring Board, is organized by NIAID and its role is to provide study oversight and evaluate clinical data to ensure safe and ethical conduct of the study.

AstraZeneca's COVID-19 shot has faced questions since late last year when the drugmaker and Oxford University published data from an earlier trial with two different efficacy readings as a result of a dosing mistake.

Later analysis suggested the dosing interval rather than the amount of dose administered was responsible for the difference.

CONFIDENCE HIT

Confidence in the vaccine took a further hit this month when more than a dozen countries, mostly in Europe, temporarily suspended the shot after reports linked it to a rare blood clotting disorder in a very small number of people.

The European Union's drug regulator said last week it was safe but an opinion poll on Monday showed Europeans remained skeptical about its safety.

The latest trial data, which has yet to be reviewed by independent researchers, was based on 141 infections among 32,449 participants.

Analysts had noted AstraZeneca's achievement of producing strong trial data against a backdrop of more infectious variants spreading in the United States and other countries.

Stephen Evans, a pharmacoepidemiology professor at London School of Hygiene & Tropical Medicine, said the up-to-date data request may have to do with efficacy readings from recent cases, which may include new variants and thus lower protection rates.

"The other vaccines may also show such reduced efficacy and we don't know by how much. It does not leave me concerned particularly unless they had found a safety issue that was being hidden, which does not appear to be the case."

The AstraZeneca vaccine is seen as crucial in tackling the spread of COVID-19 across the globe because it is easier and cheaper to transport than rival shots.

It has been granted conditional marketing or emergency use authorization in more than 70 countries.

Many countries are relying heavily on it to end the pandemic, and several state leaders have taken the shot to boost confidence in the vaccine including South Korea's President Moon Jae-in who received it on Tuesday.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-nbsp-to-publish-full-trial-data-after-U-S-rebuke-32764171/

Freeline Therapeutics started at Buy by Mizuho

 Target $27

https://finviz.com/quote.ashx?t=FRLN&ty=c&ta=1&p=d

BioLife upped to Buy from Hold by Benchmark

 Target $54

https://finviz.com/quote.ashx

Why Benitec Biopharma (BNTC) Stock Is Skyrocketing Today

 The shares of Benitec Biopharma Inc 

BNTC 82.76% are trading 92.5% higher at $6.14 in the early pre-market session on Tuesday. 

What Happened: Benitec shares had closed at $3.19 on Monday.

The surge follows Morgan Stanley MS 1.43% disclosing in a filing with the U.S. Securities and Exchange Commission after the markets closed on Monday that it had increased its stake by about 5.2% in the Australian biotechnology company.

Morgan Stanley disclosed in the 13G filing it now owned 249,174 shares in Benitec, compared to about 13,100 earlier.

Benitec is engaged in providing gene silencing therapies, combining RNA interference with gene therapy.

The company’s stock has a 52-week high of $17.39 and a 52-week low of $2.3. Benitec remained flat year-to-date as of Monday’s close, having ended 2020 at $3 per share.

https://www.benzinga.com/general/biotech/21/03/20292558/why-benitec-biopharma-bntc-stock-is-skyrocketing-today

Hoth: Positive Preclinical Results for Novel COVID-19 Therapeutic

  Hoth Therapeutics, Inc. (NASDAQ: HOTH), a biopharmaceutical company, today announced new in vitro data demonstrating SARS-CoV-2 antiviral activity for its lead peptide candidate for HT-002, a novel therapeutic targeted for the treatment of COVID-19. The data was generated in collaboration with Dr. Michael Peters, Hoth Scientific Advisory Board Member and Professor of Chemical and Life Science Engineering at Virginia Commonwealth University.

The in vitro study was conducted using a standard cytoprotection assay with live SARS-CoV-2 virus (strain USA-WA1/2020 World Reference Center for Emerging Viruses and Arboviruses, WRCEVA) and tested in Vero E6 cells using serial dilutions of the novel peptide. The lead HT-002 peptide candidate was shown to inhibit 50% of the cytopathic effect (CPE) of the SARS-CoV-2 virus at 61.7 µM (the EC50). Further, no cytotoxicity was demonstrated at concentrations of up to 200 µM of the peptide, supporting that this lead peptide has the potential to be a promising novel therapeutic for the treatment of COVID-19.

"We are encouraged by these extremely positive in vitro results supporting that HT-002's novel peptide could provide substantial antiviral activity against SARS-CoV-2," stated Dr. Stefanie Johns, Chief Scientific Officer of Hoth Therapeutics. "This data supports that HT-002 has the potential to be developed as a novel therapeutic to both prevent and treat COVID-19."

Hoth plans to pursue further preclinical animal studies to support the therapeutic potential of the lead peptide and investigate route of administration.

https://finance.yahoo.com/news/hoth-therapeutics-announces-positive-preclinical-120100913.html

Oramed Initiates Second Phase 3 Oral Insulin Study

 Oramed Pharmaceuticals Inc. (Nasdaq: ORMP) (TASE: ORMP) (www.oramed.com), a clinical-stage pharmaceutical company focused on the development of oral drug delivery systems, announced today it has screened the first patients in its ORA-D-013-2 study, the second of two concurrent Phase 3 studies of its oral insulin capsule, ORMD-0801, for the treatment of type 2 diabetes (T2D).

The studies are taking place under U.S. Food and Drug Administration (FDA) approved protocols to treat T2D patients who have inadequate glycemic control over a period of 6 to 12 months. [Enrollment for the other Phase 3 study, ORA-D-013-1, is ongoing and has surpassed 25%]. The double-blinded, placebo-controlled, multi-center randomized studies will recruit a total of 1,125 patients to evaluate the efficacy and safety of ORMD-0801. Efficacy data for the studies will become available after all patients have completed the first 6-month treatment period.

"With both concurrent Phase 3 studies now enrolling, we have achieved another world-first milestone, as the only company to conduct two Phase 3 oral insulin studies under an FDA protocol. While ORA-D-013-1 will help us evaluate our oral insulin capsule in patients who are already on two or three glucose-lowering medications, ORA-D-013-2 will help us assess our oral insulin capsule in patients who are on diet control alone or on diet and metformin monotherapy. Evaluating ORMD-0801 in these diverse population groups is expected to yield compelling results for use cases upon potential approval," stated Oramed CEO Nadav Kidron.

The ORA-D-013-2 study is recruiting 450 T2D patients with inadequate glycemic control who are managing their condition with either diet alone or with diet and metformin monotherapy. Patients will be recruited through 28 sites in the U.S. and 25 sites in Western Europe and Israel. The double-blind study will randomize patients 1:1 into two cohorts dosed with 8 mg of ORMD-0801 at night and placebo at night. The primary endpoint of the study is to compare the efficacy of ORMD-0801 to placebo in improving glycemic control as assessed by A1c over a 26-week treatment period, with a secondary endpoint of comparing ORMD-0801 to placebo in maintaining glycemic control over a 52-week treatment period.

https://finance.yahoo.com/news/oramed-initiates-second-phase-3-125100657.html