U.S. drug distributors urge govt to boost COVID-19 vaccine supply network

 Three major U.S. drug distributors have requested the government to expand the COVID-19 vaccine supply chain network as the country strives to immunize its population against the novel coronavirus as quickly as possible. AmerisourceBergen Corp, Cardinal Health Inc and Henry Schein Inc in a letter urged officials to develop a plan of action aimed at identifying ways to move the vaccines safely and quickly to administrators and vaccination sites.

The Federal Emergency Management Agency, to whom the letter was addressed, did not immediately respond to a Reuters request for comment.

The companies said on Monday the existing healthcare network, including pharmacies, doctors' offices, hospitals and other healthcare providers, will need to be activated to achieve herd immunity against the virus.

Reuters first reported in January that Cardinal Health and AmerisourceBergen Corp were in talks with federal officials about increasing the number of companies shipping coronavirus vaccines as part of the Biden administration's push to speed up inoculations.

The U.S government in February authorized Johnson & Johnson's single-dose COVID-19 vaccine for emergency use, making it the third vaccine to become available in the country, after those developed by Pfizer Inc and Moderna Inc received authorization late last year. 

https://www.marketscreener.com/quote/stock/MODERNA-INC-47437573/news/Moderna-nbsp-U-S-drug-distributors-urge-govt-to-boost-COVID-19-vaccine-supply-network-32690866/

ABBVIE IN TALKS TO SELL $5B WOMEN'S DRUGS PORTFOLIO IN MORGAN STANLEY-LED AUCTION

 https://www.marketscreener.com/news/latest/ABBVIE-INC-IN-TALKS-TO-SELL-5-BILLION-WOMEN-S-DRUGS-PORTFOLIO-IN-MORGAN-STANLEY-LED-AUCTION-SOURCE--32690966/

Fulgent Wins CDC Contract to Study Covid Variants

 Fulgent Genetics, Inc. (NASDAQ: FLGT) (“Fulgent Genetics” or the “Company”), a technology company providing comprehensive testing solutions through its scalable platform, today announced that the U.S. Centers for Disease Control and Prevention (“CDC”) has awarded the Company a contract to provide genomic sequencing of samples of SARS-CoV-2 on an ongoing basis, leveraging the Company’s Next Generation Sequencing (“NGS”) capabilities.

Under the agreement, Fulgent Genetics will sequence the genomes of random samples that have tested positive for SARS-CoV-2, the virus that causes COVID-19. Fulgent will leverage its NGS platform and provide sequencing data to the CDC as part of their initiative to conduct a large-scale genomic survey of the virus using random samples from across the United States. Ultimately, the CDC believes this large-scale genomic survey of the virus can provide important baseline information for national and state-level virus surveillance, help define important changes in transmission, help to identify unusual or emerging variants, and ultimately improve the public health response to the virus.

Fulgent believes its position as a leading provider of COVID-19 testing solutions, combined with the Company’s ability to handle large volumes of samples on its NGS platform, make the Company uniquely suited to aid the CDC in this initiative. Fulgent was selected as a partner due to its access to samples, laboratory capabilities for processing and sequencing of these samples, ability to manage the significant amount of data collected, and ability to deliver data to the CDC under the strict specifications they require.

https://www.globenewswire.com/news-release/2021/03/15/2193157/0/en/Fulgent-Genetics-Awarded-Contract-from-CDC-to-Study-Variants-of-COVID-19-Virus.html

COVID Vax in the Immunosuppressed: Reason for Concern

 Taking care of a lot of immunosuppressed patients, one big question my Johns Hopkins colleagues and I have had throughout the pandemic has been: Will vaccines rescue them from the COVID-19 threat? Based on a new study we published today in JAMA, the answer appears to be: only for some.

The day that the FDA granted the Pfizer COVID-19 vaccine an emergency use authorization, we launched a national study of vaccine immune responses in immunosuppressed solid organ transplant recipients. Among 436 COVID-naïve participants who received a first dose of mRNA vaccine, only 17% mounted detectable antibodies to SARS-CoV-2. This is in stark contrast to immunocompetent people who were vaccinated, of whom 100% mounted detectable antibody; that was true for people who had received either the Pfizer-BioNTech or Moderna vaccine. We also found that those taking anti-metabolites, such as mycophenolate or azathioprine, were about five times less likely to develop antibody responses (8.75% detectable antibody in those taking anti-metabolites versus 41.4% in those not taking them).

Naturally, we were disappointed to see these findings, as we were hoping to be able to tell our immunosuppressed patients that the vaccines seemed to work well for them. Given this observation, the CDC should update their new guidelines for vaccinated individuals to warn immunosuppressed people that they still may be susceptible to COVID-19 after vaccination. As the CDC guidelines are currently written, they assume that vaccination means immunity. Our study shows that this is unlikely for most transplant recipients, and one could guess that our findings (especially those concerning anti-metabolites) could also apply to other immunosuppressed patients, such as those with autoimmune conditions.

Of note, our previous research has not found that immunosuppressed transplant patients are at increased risk of COVID-19 mortality as we thought might be the case. But regardless, the vaccine does not seem to work as well in this same population.

As a transplant surgeon, there are a few implications for my patients. First, it seems pretty clear that immunosuppressed individuals need (at least) their second vaccine dose; proposals to stop at one dose until the rest of the population is vaccinated apply to immunocompetent people, but not to my patients. Second, it is critically important for immunosuppressed individuals to realize that they are not necessarily immune after receiving the vaccine, and to talk to their providers about antibody testing before relaxing protective behaviors. Fortunately, semiquantitative antibody tests like the ones used in our study are widely available, and correlate well with neutralizing immunity.

Our study is ongoing, and soon we will have data from the second dose, as well as deeper studies of T-cell and B-cell responses, which can confer immunity even when antibodies are not present. We are also studying other vulnerable populations. Enrollment is open, we welcome new participants, and we hope to share more information soon.

Dorry Segev, MD, PhD, is a professor of surgery and epidemiology and associate vice chair of surgery at Johns Hopkins University School of Medicine and Bloomberg School of Public Health.

https://www.medpagetoday.com/infectiousdisease/vaccines/91631

Cancer biotech Instil Bio sets terms for $250 million IPO

 Instil Bio, an early stage biotech developing cell therapies for cancer, announced terms for its IPO on Monday.

The Dallas, TX-based company plans to raise $250 million by offering 13.9 million shares at a price range of $17 to $19. At the midpoint of the proposed range, Instil Bio would command a fully diluted market value of $2.5 billion.

Instil Bio is developing a cell therapy pipeline of autologous tumor infiltrating lymphocyte (TIL) therapies for the treatment of cancer. Its lead TIL candidate, ITIL-168, is being developed for the treatment of advanced melanoma. The company plans to submit an IND and initiate a Phase 2 trial in the 2H21, which the company believes could support a BLA submission in 2023. Instil plans to initiate Phase 1 trials of ITIL-168 in additional indications with unmet medical need in the 1H22.

Instil Bio was founded in 2018 and plans to list on the Nasdaq under the symbol TIL. Morgan Stanley, Jefferies and Cowen are the joint bookrunners on the deal. It is expected to price during the week of March 15, 2021.

Relevant Profile: TIL

https://www.renaissancecapital.com/IPO-Center/News/79354/Cancer-biotech-Instil-Bio-sets-terms-for-$250-million-IPO

Jefferies spins positive on Lilly phase 2 Alzheimer's win, with questionable secondaries, significance

 Eli Lilly has shared full data from a phase 2 clinical trial it hailed as showing a “significant slowing of decline” in Alzheimer’s disease patients. The donanemab data are a mixed bag, with a slight win on one disease scale undermined by a failure on a more widely used measure of Alzheimer’s.

In January, Lilly revealed donanemab, formerly known as LY3002813, improved a composite measure of cognition and daily function in patients with early symptomatic Alzheimer’s. The finding, in a field defined by repeated failures, was a rare glimmer of hope and offered encouragement for people who take a positive view of Biogen’s similar drug candidate aducanumab.

Full data from the 257-subject clinical trial, published in The New England Journal of Medicine, show patients on donanemab experienced a 6.86 decline in scores on the Integrated Alzheimer’s Disease Rating Scale (iADRS). Scores in the placebo group fell 10.06. Lower iADRS scores indicate greater cognitive and functional impairment.

The difference between the iADRS scores was enough for the trial to hit its primary endpoint with a p-value of 0.04. Analysts at Jefferies hailed the result as a positive for Lilly and the broader effort to treat Alzheimer’s by targeting amyloid. 

“LLY's positive Phase II donanemab study adds another (+) datapoint for Abeta antibodies (and BIIB) that directly target and remove plaque and wisely enrich for milder pts,” the analysts wrote in a note to investors. 

However, more skeptical readings of the data are possible, in part because it is unclear exactly what the narrow statistical improvement in iADRS scores means in terms of clinical outcomes.

Lilly has used iADRS, which combines scores from the better established ADAS-Cog and ADCS-iADL, across multiple trials. In the solanezumab phase 3 clinical trials, iADRS was the only measure that consistently found the drug performed better than placebo. Two of those trials failed the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB) endpoint but hit on iADRS.

The donanemab data reveal a similar divergence between iADRS and CDR-SB results. In the phase 2, Lilly found donanemab had no statistically significant effect on CDR-SB over placebo. The success on iADRS, which is little used outside of Lilly, and failure on the well-understood CDR-SB complicates efforts to understand what the apparent effects of donanemab mean in practical terms for patients. Lilly achieved the results in a carefully selected population, with 257 of the 1,955 patients assessed meeting the eligibility criteria and joining the study.

Lilly is running a second, 500-subject phase 2 clinical trial that uses change in CDR-SB as the primary goal, with iADRS serving as a secondary endpoint. The Jefferies analysts see potential for Lilly to frame the phase 2 program as a success on the strength of two hits against the iADRS endpoints.

“While FDA considers CDR-sb a regulatory endpoint, we don't get any sense investors would see a major issue if LLY had two positive studies on iADRS and presumably LLY remains in close dialog with FDA,” the analysts wrote. 

Lilly's shares opened down 7% in early trading Monday morning.

Missing the CDR-SB endpoint prevented Lilly from forming definite conclusions about its other secondary objectives. Patients on donanemab performed better numerically on multiple measures, but it is unclear whether the results reflect benefits delivered by the drug. 

Lilly more conclusively showed that donanemab, which zeroes in on amyloid plaques, reduces levels of the aggregates of misfolded proteins in the brain. On the safety and tolerability front, incidence of ARIA-E—amyloid-related imaging abnormalities—affected 26.7% of patients on donanemab and caused symptoms in 6.1% of people on the drug. The rate of ARIA-E in the placebo arm was 0.8%.

Patients on aducanumab have also developed ARIA-E. That was one of many data points analysts compared between the aducanumab and donanemab trials. The Jefferies analysts, who think aducanumab has a good shot at winning approval, presented a positive take on the Lilly data for Biogen.

“We could argue the data was promising and adds to the hypothesis for approving - but not too good such that it would obviously be better than Adu on efficacy and/or for potential competitor market share in the future,” the analysts wrote.

https://www.fiercebiotech.com/biotech/lilly-s-phase-2-alzheimer-s-win-marred-by-missed-secondaries-questions-about-clinical

Ocugen plans to sell 100M Indian vaccine doses in U.S. in 2021

 Ocugen Inc plans to sell 100 million doses of India's state-backed COVID-19 vaccine in the United States this year, the U.S. firm's chief executive Shankar Musunuri told Reuters on Monday.

Musunuri said Ocugen, a Pennsylvania-based biopharmaceutical firm, was aiming to launch the Indian-developed vaccine in the United States in the second quarter of 2021, initially with imported shots before beginning production there.

The United States has already authorised COVID-19 vaccines developed by Pfizer/BioNTech, Moderna and Johnson & Johnson for emergency use.

India's two-dose COVAXIN has been found to be 81% effective in an interim analysis of late-stage trial data on some 26,000 people in India, its developers Bharat Biotech and the state-run Indian Council of Medical Research said this month.

Bharat Biotech says as many as 40 countries are interested in COVAXIN and it has already sought emergency approvals in Brazil and the Philippines. Cracking the U.S. market would be a significant milestone for the company and India's vaccine industry, which is the world's largest.

Musunuri said Ocugen had held initial talks with the U.S. Food and Drug Administration and planned to seek emergency use authorisation in April.

"They're fine with the way the interim analysis is being done," Musunuri said, adding that Ocugen had "a regulatory path" to take the process forward.

Musunuri said COVAXIN had the potential to work against COVID-19 variants and Ocugen could initially focus on children as it was likely to be safe for those over the age of 12, while shots produced by other drugmakers targeted adults.

Pfizer's vaccine has been authorised for emergency use in the United States for individuals 16 years and older, with the other two given authorisation for emergency use in people 18 years and above.

"Like a polio virus given to babies, this could be safe for all children, high-risk groups, pregnant women and people with comorbidities," Musunuri said of COVAXIN.

BOOSTER SHOT

He said Ocugen was expecting more data from Bharat Biotech on COVAXIN, following up on a study by the Indian company in January which showed the shot was likely to be effective against the British strain of the coronavirus.

India's drug regulator approved COVAXIN for emergency use in January for people above 12, saying it could act against the whole body of a virus instead of just its "spike-protein" tip, potentially making it more effective in case of mutations.

Musunuri said this could mean it could be used as a booster for people already vaccinated with a first dose of other shots.

He said Bharat Biotech would export "tens of millions of doses" to Ocugen, which is also finalising U.S. contract- manufacturers for the product.

Ocugen will have the U.S. rights to the vaccine and will be responsible for its clinical development, regulatory approval and commercialisation there. Bharat Biotech will also transfer its technology, and keep 55% of the profit.

Shares in Ocugen have nearly tripled this year, taking it close to a $2 billion market capitalisation, helped by a spike when Bharat Biotech announced its late-stage trial results.

COVAXIN has been given to more than 2 million prioritised adults in India since the country's vaccination drive began in mid-January. Bharat Biotech says it wants to produce about 700 million doses a year domestically.

https://www.marketscreener.com/quote/stock/OCUGEN-INC-19157135/news/Ocugen-plans-to-sell-100-mln-Indian-vaccine-doses-in-U-S-in-2021-32690073/