Travere lines up another shot at speedy sparsentan approval

 In May the FDA knocked back Travere’s attempt to win accelerated approval for sparsentan in focal segmental glomerulosclerosis, demanding more data. Encouraging early results in another rare kidney disease, IgA nephropathy, have persuaded the company to try again. A first-half 2022 filing is planned, backed by interim data from the Protect trial, which found a statistically significantly greater reduction in proteinuria, a biomarker used to track the disease, in patients treated with sparsentan versus irbesartan, a long generic hypertension medication. Sparsentan also reduces blood pressure but is mechanistically different from irbesartan and other anti-hypertensives used off-label for IgAN. No data were disclosed on estimated glomerular filtration rate (eGFR), a kidney function endpoint that must be hit for full approval; on a call executives said preliminary eGFR details were “consistent with our powering and indicative of a clinically meaningful result”. Is this is enough for the FDA? The project looks competitive with Calliditas’s steroid-based Nefecon, due an accelerated approval decision in IgAN in September; that filing did include eGFR data. Cross-trial comparisons are always imperfect, but with nothing approved for IgAN perhaps the most important point here is that both look effective.

IgAN rivals? Cross-trial comparison of Nefecon and sparsentan
	Calliditas, Nefigard part A: Nefecon vs placebo		Travere, interim readout from Protect: sparsentan vs irbesartan
Endpoint	Nefecon 16mg	Placebo	Sparsentan 400mg	Irbesartan 300mg
Mean reduction in proteinuria vs baseline*	31%	5%	49%	15%
Change in eGFR**	0.17ml/min/1.73m2 decline	4.04ml/min/1.73m2 decline	?	?
Note: Nefigard patients remained on existing hypertensive medication; Protect patients were switched to sparsentan or irbesartan, and steroid use excluded.  *Measured at 9 mths in Nefigard and 36 wks in Protect; **Measured at 9 mths in Nefigard, to be measured at 1 yr+ in Protect. Part B of Nefigard will provide long term data for full approval. Source: company releases & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/snippets/travere-lines-another-shot-speedy-sparsentan-approval

Lilly leaves investors itching for more details

 Lilly and Almirall’s atopic dermatitis contender lebrikizumab has prevailed in its pivotal trials, Advocate 1 and 2. But, other than the groups saying “more than half” of patients achieved 75% skin clearance, or Easi-75, details were thin on the ground. Investors will have to wait for an undisclosed 2022 medical meeting to see whether lebri has held its own in a cross-trial comparison against Sanofi and Regeneron’s Dupixent. The signs are good: in Dupixent’s pivotal trials, 51 and 44% of patients receiving the drug every other week met Easi-75 on a non-placebo-adjusted basis. It will also be important to see how lebri performed on its second co-primary endpoint, the proportion of patients with an IGA score of 0 or 1. Another factor is how different dosing regimens of lebri fared: patients received the drug every two or four weeks, potentially giving lebri a convenience advantage over Dupixent. Finally, safety will be on the agenda as it is hoped that lebri could sidestep the issue of conjunctivitis, which occurred in 10% of patients in Dupixent’s monotherapy trials. Lilly said today that conjunctivitis was one of the most common adverse events seen with lebri, so actual numbers will be keenly awaited.  

Awaiting detailed data: what lebri needs to do in phase 3
Endpoint	Dupixent ph3*	Lebri ph2**
IGA 0 or 1	27-28 points	19-30 points
EASI-75	32-36 points	32-37 points
EASI-90	23-28 points	25-33 points
Note: all values placebo-adjusted; *monotherapy ph3 trials (Solo-1 & Solo-2); **250mg every 4wks & 250mg every 2wks, all secondary endpoints. Source: Dupixent label & JAMA Dermatology.

 

Lebri's phase 3 trials
Study name/ID	Details	Data
Advocate 1, NCT04146363	Placebo-controlled, lebri monotherapy every 2/4 wks	Topline data released; positive
Advocate 2, NCT04178967	Placebo-controlled, lebri monotherapy every 2/4 wks	Topline data released; positive
Adhere, NCT04250337	Placebo-controlled, lebri + topical corticosteroids every 2 wks	Completes Aug 2021
Adore, NCT04250350	Adolescents, single-arm, lebri every 2 wks	Completes Apr 2022
Adjoin, NCT04392154	Long-term extension, lebri every 2/4 wks	Completes May 2024
Source: Evaluate Pharma & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/snippets/lilly-leaves-investors-itching-more-details

Pfizer, BioNTech File Initial Data to FDA to Support Covid Booster

 Pfizer Inc. and BioNTech SE on Monday said they have submitted Phase 1 data to the U.S. Food and Drug Administration to support the evaluation of a booster dose of their Covid-19 vaccine.

The partners said individuals in the study who received a third dose showed a favorable safety profile and robust immune responses, with the booster dose eliciting significantly higher neutralizing antibody titers against the initial SARS-CoV-2 virus, as well as the Beta and Delta variants, compared to levels seen after the two-dose primary series.

Pfizer and BioNTech said a booster dose given within six to 12 months after the primary vaccination schedule may help maintain a high level of protection against Covid-19, and that they plan to seek FDA approval of a third dose in individuals ages 16 and older.

Amid a surge in Covid-19 cases tied to the Delta variant, the FDA last week authorized booster shots for certain people with weakened immune systems, and the agency said it was reviewing whether an additional dose may be needed in other people who are fully vaccinated.

Pfizer and BioNTech said they plan to file the Phase 1 study data to the European Medicines Agency and other regulatory authorities in the coming weeks, adding that they shortly expect Phase 3 results evaluating the third dose, which they will also submit to regulators around the world.

https://www.marketwatch.com/story/pfizer-biontech-file-initial-data-to-fda-to-support-covid-19-vaccine-booster-dose-271629129246

Taiwan Rejects COVID Vaccine Candidate, President to Get Domestic Shot

 Taiwan has rejected an application for the emergency use of UBI Pharma's COVID-19 vaccine candidate, the government said on Monday, though the president said she would get a separate domestic shot in a show of support for the scheme.

Although Taiwan has ordered millions of Moderna and AstraZeneca shots, developing a local vaccine has been a major goal and it is due next week to start administering its first domestic vaccine, made by Medigen Vaccine Biologics.

The health ministry, explaining the rejection of the request for emergency use authorisation (EUA), said the antibodies triggered by UBI's candidate did not match up with those of the AstraZeneca vaccine.

However, the ministry said, UBI planned Phase III trials in India.

Health Minister Chen Shih-chung expressed regret that the EUA had not been granted. "We still have to follow certain standards," he told reporters.

UBI, whose share price closed 30% down on Monday following the rejection, said in a statement to the stock market it saw a limited financial hit from the decision and that it would re-evaluate the "benefit assessment" of the phase three clinical trial. It did not elaborate.

In June, the company had said it would seek an EUA in Taiwan and that Phase II tests showed no major adverse effects for its candidate, which, it said, generated a good immune response.

The government has drawn criticism from opposition parties after President Tsai Ing-wen initially pledged to start administering domestically developed vaccines in July, before results of second clinical trials were released.

Later, Tsai said Taiwan would strictly scrutinise the process according to global scientific norms and put safety first.

https://www.usnews.com/news/world/articles/2021-08-16/taiwan-rejects-covid-vaccine-candidate-president-to-get-domestic-shot

Bayer takes legal battle over Roundup cancer claims to U.S. Supreme Court

 Bayer, trying to contain billions of dollars in legal costs, filed a petition with the U.S. Supreme Court to reverse an appeals court verdict that upheld damages to a customer blaming his cancer on the German group's glyphosate-based weedkillers.

Bayer last week lost a third appeal against verdicts that sided with users of glyphosate-based Roundup, awarding them tens of millions of dollars each, leaving the drugs and pesticides group to pin hopes for relief on the United States' top court.

Bayer on Monday asked the Supreme Court to review one such verdict by the federal 9th U.S. Circuit Court of Appeals that found in favour of California resident and Roundup user Edwin Hardeman, it said in a statement.

The maker of aspirin, Yasmin birth-control pills and stroke prevention drug Xarelto has repeatedly argued that the cancer claims over Roundup go against sound science and product clearance from the federal environmental regulator.

“The Ninth Circuit’s errors mean that a company can be severely punished for marketing a product without a cancer warning when the near-universal scientific and regulatory consensus is that the product does not cause cancer, and the responsible federal agency has forbidden such a warning," the company said.

Roundup-related lawsuits have dogged the company since it acquired the brand as part of its $63 billion purchase of agricultural seeds and pesticides maker Monsanto in 2018.

Bayer struck a settlement deal in principle with plaintiffs last year but failed to win court approval for a separate agreement on how to handle future cases, as it intended to keep the product on the market.

Last month, it took an additional litigation provision of $4.5 billion to cover any unfavourable ruling by the Supreme Court. That came on top of $11.6 billion it previously set aside for settlements and litigation over the matter.

Among other measures to contain the legal onslaught, Bayer plans to replace glyphosate in weedkillers for the U.S. residential market with other active ingredients.

It will, however, continue to sell the herbicide to farmers, who rely on it heavily, and whose role in the litigation has been described as negligible by Bayer.

https://news.yahoo.com/bayer-takes-legal-battle-over-144416209.html

EU evaluates Roche arthritis drug as COVID-19 treatment

 Europe's drugs regulator said on Monday it was evaluating the use of Roche's arthritis drug, Actemra, in hospitalised adults with severe COVID-19, its latest review of a potential coronavirus treatment.

Tocilizumab, sold by Roche as Actemra and RoActemra, has shown promise in clinical trials in treating COVID-19, and was approved by U.S. health regulators in June for emergency use in hospitalized COVID-19 patients who needed oxygen.

A large trial in February showed that tocilizumab cut the risk of death among patients hospitalised with severe COVID-19, shortened the time to recovery and reduced the need for mechanical ventilation.

The European Medicines Agency (EMA) will carry out an accelerated assessment of the drug, including results from four large studies, it said in a statement. The outcome is expected in mid-October.

The EMA is also evaluating an application for an arthritis drug developed by Sweden's Sobi to treat COVID-19 in adults with pneumonia, and Eli Lilly's rheumatoid arthritis drug Olumiant to treat hospitalised COVID-19 patients receiving oxygen.

Other treatments under a rolling review in the European Union include antibodies or antibody cocktails developed by Eli Lilly, Celltrion and Regeneron, and one jointly developed by GlaxoSmithKline and Vir Biotechnology.

Gilead's remdesivir is the only drug currently authorised to treat COVID-19 in the European Union.

https://finance.yahoo.com/news/1-eu-evaluates-roche-arthritis-124044812.html

Glaxo/CureVac Gen-2 mRNA COVID-19 Vaccine Preclinical Candidate Improves Immune Response, Protection

 

• Preclinical study provides evidence for strongly improved immune responses with second-generation mRNA backbone jointly developed by CureVac and GSK compared to CureVac's first-generation mRNA backbone

• Data demonstrate high protective efficacy of second-generation lead candidate, CV2CoV, in animal model during SARS-CoV-2 challenge study

• Neutralizing capacity of induced antibodies tested against a range of variants, including the Beta, Delta and Lambda variant

CureVac N.V. (Nasdaq:CVAC), a global biopharmaceutical company developing a new class of transformative medicines based on messenger ribonucleic acid ("mRNA"), and GSK today announced the publication of preclinical data investigating immune responses as well as the protective efficacy of CureVac's first-generation vaccine candidate, CVnCoV, and second-generation vaccine candidate, CV2CoV, against SARS-CoV-2 challenge in non-human primates. The study assessed cynomolgus macaques vaccinated with 12µg of either the first or second-generation vaccine candidate. Better activation of innate and adaptive immune responses was achieved with CV2CoV, resulting in faster response onset, higher titers of antibodies and stronger memory B and T cell activation as compared to the first-generation candidate, CVnCoV. Higher antibody neutralizing capacity was observed with CV2CoV across all selected variants, including the Beta, Delta and Lambda variants. During challenge with the original SARS-CoV-2 virus, animals vaccinated with CV2CoV were found to be better protected based on highly effective clearance of the virus in the lungs and nasal passages. The full manuscript of the preclinical data is available on the preprint server bioRxiv.

"In this animal model, CV2CoV is shown to induce broad antibody and cellular immune responses very similar to the breadth of the immune responses observed after infection with SARS-CoV-2," said Dr. Igor Splawski, Chief Scientific Officer of CureVac. "The current study shows that the immune responses and resulting protection produced by our second-generation candidate, based on our mRNA technology featuring targeted optimizations, are substantially improved in non-human primates against both the original SARS-CoV-2 virus as well as the Beta and Delta Variants of Concern and the Lambda Variant of Interest."

Within the study, CVnCoV and CV2CoV were tested in cynomolgus macaques immunized with a 12µg dose of the respective candidate on day 0 and day 28. Induction of innate immunity was investigated via specific cytokine markers. Adaptive immune responses were assessed based on receptor binding domain specific antibodies and neutralizing antibodies as well as memory B and T cells. Impact of Variants of Concern and Variants of Interest on neutralizing antibody titers was tested against the Alpha, Beta, Delta, Kappa and the Lambda variant. Clearance of the virus in the lungs and nasal passages of the animals was tested following challenge infection with the original virus.

The CureVac-GSK COVID-19 collaboration announced in February 2021 extends the existing strategic mRNA technology partnership both companies started in July 2020, which focuses on the development of new products based on CureVac's second-generation mRNA technology for different targets in the field of infectious diseases. The optimized mRNA backbone that is being used in this collaboration also has the potential for a multivalent or combination approach to address multiple emerging variants in one vaccine. Following the current preclinical development of CV2CoV, a Phase 1 clinical trial is expected to start in Q4 2021.

https://finance.yahoo.com/news/second-generation-mrna-covid-19-111500747.html