AstraZeneca says Pfizer results encouraging for vaccine developers

An AstraZeneca executive said he felt encouraged by “incredibly promising” large-scale COVID-19 vaccine trial results unveiled by Pfizer and its German partner BioNTech on Monday.

Speaking at a Financial Times online conference on healthcare, Astra senior executive team member Ruud Dobber said the first efficacy data release made him optimistic that Astra too would be able to follow up on positive results from early-stage trials.

Pfizer and BioNTech’s experimental vaccine was shown to be more than 90% effective based on initial late-stage trial results, the companies said on Monday.

AstraZeneca, working with the University of Oxford, expects to report late-stage trial data on its COVID-19 immunisation before year-end.

“What we have seen in Phase I and Phase II - whether it is Pfizer or AstraZeneca with our Oxford vaccine - is that if you are able to generate neutralising antibodies and a good T-cell response that you can make the virus less hostile,” Dobber said.

“The efficacy shown earlier today is incredibly promising and I really hope that more vaccine producers will showcase more or less the same results sooner rather than later,” he added.

https://www.reuters.com/article/us-health-coronavirus-astrazeneca/astrazeneca-says-pfizer-results-encouraging-for-vaccine-developers-idUSKBN27P2JL

FDA Action Alert: Supernus, Adamis, Alkermes, Amgen, BMS and Eiger

November is promising to be a busy month for the U.S. Food and Drug Administration (FDA) in terms of PDUFA dates. Here’s a look at some of the upcoming target action dates on the FDA’s calendar. 

Supernus Pharmaceuticals’ SPN-812 for ADHD

Supernus Pharmaceuticals has a target action date of November 8, 2020 for SPN-812 for the treatment of attention deficit hyperactivity disorder (ADHD). SPN-812 is a serotonin norepinephrine modulating agent (SNMA). The active ingredient is violaxazine hydrochloride, which has an extensive safety record in Europe, where it was previously marketed as an antidepressant.

The New Drug Application (NDA) for the drug is based on data from four Phase III trials in pediatric patient populations from the age of 6 to 17 years, two Phase II trials, several Phase I trials, a long-term open label extension study, preclinical testing, and drug manufacturing data. The company is also still conducting a Phase III trial in the adult ADHD patient population.

Adamis Pharmaceuticals’ Zimhi for Opioid Overdose

Adamis Pharmaceuticals has a target action date of November 15 for its Zimhi (naloxone) for opioid overdose. The NDA was resubmitted on May 2020. The resubmission came after a meeting with the FDA in February 2020 and addresses issues raised by the agency’s Complete Response Letter (CRL) in November 2019.

“We have been encouraged by our interactions with the FDA following our CRL and are pleased to resubmit our Zimhi NDA,” said Dennis J. Carlo, president and chief executive officer of Adamis, in May 2020. “Based on the feedback from our Type A meeting in February, we conducted additional product testing with the goal of addressing the Chemistry, Manufacturing and Controls deficiencies discussed in the CRL.”

Alkermes’ ALKS 3831 for Schizophrenia and Bipolar I Disorder

Alkermes has a target action date of November 15 for ALKS 3831 (olanzapine/samidorphan) for the treatment of schizophrenia and for the treatment of bipolar I disorder. The drug is an investigational, novel, once-daily, oral atypical antipsychotic drug candidate designed to improve the efficacy of olanzapine while decreasing olanzapine-associated weight gain.

The submission includes data from the ENLIGHTEN clinical development program in schizophrenia, and pharmacokinetic (PK) bridging data comparing ALKS 3831 and Zyprexa (olanzapine), to support an indication for schizophrenia. There is also data supporting treatment of manic or mixed episodes linked with bipolar I disorder as a monotherapy or adjunct to lithium or valproate for maintenance of bipolar I disorder.

Amgen’s Kyprolis in R/R Multiple Myeloma

Amgen has a target action date of November 15 for the supplemental NDA (sNDA) for Kyprolis in combination with dexamethasone and Darzalex (daratumumab) for relapsed or refractory (R/R) multiple myeloma. The sNDA was built on data from the Phase III CANDOR trial.

In September 2019, the company announced the CANDOR trial met its primary endpoint of progression-free survival (PFS), showing a 37% decrease in the risk of progression or death in patients with r/r multiple myeloma treated with dexamethasone and Darzalex.

“The potential to combine Kyprolis and Darzalex, two powerful targeted agents, represents an additional therapeutic approach for patients with relapsed or refractory multiple myeloma,” said David M. Reese, executive vice president of Research and Development at Amgen. “The results from the CANDOR study confirm the potential for Kyprolis to be used in combination with an anti-CD38 monoclonal antibody.”

Bristol Myers Squibb’s Lisocabtagene Maraleucel (CAR-T) for R/R Large B-Cell Lymphoma

Bristol Myers Squibb has a target action date of November 16 for the biologics license application (BLA) for lisocabtagene maraleucel (liso-cel), a CD19-directed CAR T cell therapy for adults with r/r large B-cell lymphoma after at least two previous therapies. Prior to the submission and acceptance of the SBA, ZBMS had submitted additional data, which the agency defined as a major amendment to the application and would require additional time for review.

Bristol Myers Squibb picked up liso-cel when it acquired Celgene. Celgene acquired it in 2018 from bluebird bio, who originally developed the therapy. When BMS was putting in its bid for Celgene, the two companies could not agree on the long-term value of Zeposia (ide-cel), which is approved for multiple sclerosis, and liso-cel. To close the deal, they agreed that if Zeposia and liso-cel were approved by December 31, 2020, and ide-cel by March 31, 2021, Bristol Myers Squibb would pay another $9 per share via a Contingent Value Right (CVR). This seemed likely until the FDA pushed back the ide-cel review.

Eiger BioPharmaceuticals’ Zokinvy for Progeria and Progeroid Laminopathies

Eiger BioPharmaceuticals has a target action date of November 20 for Zokinvy (lonafarnib) for Progeria and Progeroid Laminopathies. This is under Priority Review. The NDA included data from Phase III trial demonstrating a survival benefit with an 88% decrease in the risk of mortality in patients with Progeria treated with Ionafarnib monotherapy. Progeria, also called Hutchinson-Gilford Progeria Syndrome (HGPS), is an ultra-rare and fatal genetic disease of accelerated aging in children. It is caused by a point mutation in the LMNA gene, which codes for the lamin A protein, resulting in the farnesylated aberrant protein, progerin. Without Ionafarnib therapy, children with Progeria die of artheroschlerosis, but at an average age of 14.5 years. Progeroid Laminopathies are similar, caused by a number of mutations in the lamin A and/or Zmpste24 genes.

“The acceptance of our first NDA is a significant milestone for Eiger, and an important step toward bringing a treatment to children and young adults with Progeria and Progeroid Laminopathies,” said David Cory, president and chief executive officer of Eiger.

https://www.biospace.com/article/fda-action-alert-supernus-adamis-alkermes-amgen-bms-and-eiger/

Could SARS-CoV-2 evolve resistance to COVID-19 vaccines?

Similar to bacteria evolving resistance to antibiotics, viruses can evolve resistance to vaccines, and the evolution of SARS-CoV-2 could undermine the effectiveness of vaccines that are currently under development, according to a paper published November 9 in the open-access journal PLOS Biology by David Kennedy and Andrew Read from Pennsylvania State University, U.S. The authors also offer recommendations to vaccine developers for minimizing the likelihood of this outcome. 

"A COVID-19 vaccine is urgently needed to save lives and help society return to its pre-pandemic normal," said David Kennedy, assistant professor of biology. "As we have seen with other diseases, such as pneumonia, the evolution of resistance can quickly render vaccines ineffective. By learning from these previous challenges and by implementing this knowledge during vaccine design, we may be able to maximize the long-term impact of COVID-19 vaccines."

The researchers specifically suggest that the standard blood and nasal-swab samples taken during clinical trials to quantify individuals' responses to vaccination may also be used to assess the likelihood that the vaccines being tested will drive resistance evolution. For example, the team proposes that blood samples can be used to assess the redundancy of immune protection generated by candidate vaccines by measuring the types and amounts of antibodies and T-cells that are present.

"Much like how combination antibiotic therapy delays the evolution of antibiotic resistance, vaccines that are designed to induce a redundant immune response—or one in which the immune system is encouraged to target multiple sites, called epitopes—on the virus's surface, can delay the evolution of vaccine resistance," said Andrew Read, Evan Pugh Professor of Biology and Entomology and director of the Huck Institutes of the Life Sciences. "That's because the virus would have to acquire several mutations, as opposed to just one, in order to survive the host immune system's attack."

The researchers also recommend that nasal swabs typically collected during clinical trials may be used to determine the viral titer, or amount of virus present, which can be considered a proxy for transmission potential. They noted that strongly suppressing virus transmission through vaccinated hosts is key to slowing the evolution of resistance, since it minimizes opportunities for mutations to arise and reduces opportunities for natural selection to act on those mutations that do arise.

In addition, the team suggests that the genetic data acquired through nasal swabs can be used to examine whether vaccine-driven selection has occurred. For example, differences in alleles, or forms of genes that arise from mutations, between the viral genomes collected from vaccinated versus unvaccinated individuals would indicate that selection has taken place.

"According to the World Health Organization, at least 198 COVID-19 vaccines are in the development pipeline, with 44 currently undergoing clinical evaluation," said Kennedy. "We suggest that the risk of resistance be used to prioritize investment among otherwise similarly promising vaccine candidates." 

More information: PLOS Biology (2020). DOI: 10.1371/journal.pbio.3001000

https://medicalxpress.com/news/2020-11-sars-cov-evolve-resistance-covid-vaccines.html

Russia's Sputnik V vaccine also over 90% effective: health ministry

Russia’s Sputnik V vaccine against COVID-19 is more than 90% effective, a representative of the health ministry said on Monday, citing data collated from vaccinations of the public rather than from an ongoing trial.

The comments followed a statement earlier on Monday by vaccine developers Pfizer Inc and BioNTech BNTX.O, who said their experimental COVID-19 vaccine was more than 90% effective.

“We are responsible for monitoring the effectiveness of the Sputnik V vaccine among citizens who have received it as part of the mass vaccination programme,” Oksana Drapkina, director of a research institute under the health ministry, said in a statement.

“Based on our observations, its effectiveness is also more than 90%. The appearance of another effective vaccine - this is good news for everyone,” Drapkina said.

Russia is rolling out the vaccine for domestic use despite the fact that late-stage trials have not yet finished.

Earlier on Monday, Alexander Gintsburg, director of Moscow’s Gamaleya Institute which developed the Russian vaccine candidate, said he welcomed the Pfizer news.

“In the near future we expect to publish interim results of the post-registration trial of the vaccine Sputnik V, the so-called Phase III trials. I am sure that its effectiveness level will also be high,” he said.

Russia is gearing up to publish preliminary results of an ongoing large-scale human trial, known as Phase III, this month. It is testing the vaccine on 40,000 people in Moscow.

https://www.reuters.com/article/health-coronavirus-russia-vaccine-int-idUSKBN27P212