Theravance COVID-19 therapy shows potential in mid-stage study

 

• TD-0903, an inhaled pan-JAK inhibitor being developed by Theravance Biopharma (TBPH -3.4%) has demonstrated a favorable impact in hospitalized patients with severe COVID-19, according to data from a Phase 2 trial.
• The findings published in a pre-print pending a peer-review indicate that in the trial where 25 patients were randomized to receive TD 0903 or placebo, TD-0903 was generally well tolerated with no treatment-related serious adverse events.
• The clinically favorable numerical trends included lower mortality, shorter hospitalization, better oxygenation as well as what researchers identified as improved 8-point clinical status.
• Based on Part 1 of this phase 2 trial, the paper concluded the potential of TD-0903 in the treatment of patients with severe COVID-19.
• Theravance Biopharma initiated the dosing of Part 1 of Phase 2 study of TD-0903 in June and the second part of the trial, a larger multi-center study is currently in progress involving 198 hospitalized patients with COVID-19.

https://newsfilter.io/a/97e880efac3fd062cb6434198202bce8

Biden, ‘Quad’ alliance plan to boost COVID-19 vaccine in Asia

 President Biden and leaders in India, Japan and Australia on Friday are banding together to boost COVID-19 vaccine supply in Asian countries, according to multiple reports.

The joint effort between the US and the so-called “Quad” alliance — short for Quadrilateral Security Dialogue — will be announced during a virtual meeting, a senior administration official told Fox News.

The deal seeks to address vaccine shortages in Southeast Asia and develop 1 billion vaccines by 2022. It will also establish a senior-level group of vaccination experts.

The 90-minute meeting will be moderated by Secretary of State Tony Blinken and attended by Biden, Australian Prime Minister Scott Morrison, Indian Prime Minister Narendra Modi and Japanese Prime Minister Yoshihide Suga.

Other topics of discussion will include the Paris Climate Accord, which Biden re-entered on his first day in office, trade and economic cooperation, climate change and technology development.

Suga will be the first world leader to visit Biden at the White House, according to administration officials. Details of that meeting have not been determined.

Meanwhile, Blinken and Defense Secretary Lloyd Austin will travel to meet with their Japan and South Korea counterparts in the coming days, Fox News said.

https://nypost.com/2021/03/12/biden-asia-alliance-announcing-plans-to-boost-covid-vaccine/

Aelix posts HIV vaccine data ahead of Gilead combo readout

 Aelix Therapeutics has presented phase 1/2a data on its therapeutic HIV vaccine candidate. Buoyed by the results, Gilead-partnered Aelix is preparing to raise cash and push into larger trials in pursuit of a functional cure for the disease.

Spain-based Aelix initiated the clinical trial in 2017 to evaluate a prime-boost vaccination regimen. Participants were randomized to receive placebo or a vaccine regimen that combined a mix of DNA, modified vaccinia ankara virus and adenovirus vectors with a sequence chosen to direct the immune system to the most vulnerable parts of the HIV virus.

To evaluate whether the HTI vaccine could keep the HIV virus suppressed in the absence of antiretroviral treatment (ART), the trial enrolled 45 patients, 41 of whom received the full mix of viral vectors or placebo doses and entered the 24-week analytical treatment interruption stage of the study. 

In presenting the data at the Conference on Retroviruses and Opportunistic Infections, Aelix focused on a subset of patients. In the 32 patients who lacked specific HLA class I alleles, giving them favorable genetics, 40% of the participants who took the vaccine remained off ART for 22 weeks. Only 8% of patients on placebo stayed off ART for that long.

The abstract shared at the conference lacks data points relevant to the prospects of the vaccine, but Aelix and its associates are upbeat about the results, which the University of Melbourne’s Sharon Lewin, Ph.D., said have “convincingly shown that the HTI vaccines can generate immune control.” Immunizations were well tolerated and triggered at least a twofold jump in HTI-specific T-cell responses in 97% of people. 

Aelix CEO José Luis Cabero said the biotech is now “looking forward to moving ahead with the next financing round and working on larger combination trials.” Gilead partnered with Aelix in 2018 to assess the effect of giving its TLR7 agonist in combination with the T-cell vaccine, leading to the initiation of a clinical trial that year. Data from the phase 2a are due late in 2022. 

https://www.fiercebiotech.com/biotech/aelix-posts-hiv-vaccine-data-ahead-gilead-combo-readout

Abbott launches pandemic defense coalition to detect future variants, outbreaks

 A year into this global pandemic, Abbott is preparing for the next one: the medtech giant has launched a network of centers with expertise in lab testing, genetic sequencing and public health to help catch and track emerging viruses and potentially dangerous mutations.

The goal of the company’s Pandemic Defense Coalition is to help develop diagnostic tests quickly as new threats are discovered and to publish their sequencing findings publicly so others can help determine if the disease is a novel strain.

"We cannot fight what we cannot see coming,” said Abbott’s head of infectious disease research, Gavin Cloherty, describing the program as “eyes on the ground” for the global public health community.

"The COVID-19 pandemic has demonstrated a clear need for advanced surveillance and viral sequencing—and the critically important role of testing,” Cloherty added. "Our goal is to help prevent history from repeating itself."

The coalition currently includes academic centers and nonprofit organizations in Chicago, Jamaica, Colombia, Brazil, South Africa, Senegal, India and Thailand. The company said it is in talks to sign on additional public and private organizations.

Surveillance will start with local physicians identifying patients with unknown conditions, and having their samples sequenced and shared throughout the network. If a threat is discovered, Abbott will use the data to help develop diagnostics to aid in containing the outbreak, while also working on tests for COVID-19, HIV, malaria and hepatitis.

Abbott previously launched its Global Viral Surveillance Program over 25 years ago to monitor HIV and hepatitis; that program will be folded into the new pandemic coalition.

"In a sophisticated network like the Abbott Pandemic Defense Coalition, we have access to best-in-class science and technology that makes data collection, analysis and sharing efficient and effective," said Souleymane Mboup, president of Institut de Recherche en Santé, de Surveillance Epidemiologique et de Formations in Dakar, Senegal. 

"The key here is collaboration; no single lab or organization in any one country would be able to conduct testing and analysis of this breadth and scale but connecting global centers of excellence makes it possible for us all to assist in identifying the next potential threats to public health," Mboup said.

https://www.fiercebiotech.com/medtech/abbott-launches-pandemic-defense-coalition-to-detect-future-variants-outbreaks

Novavax links vaccine to full protection against severe COVID-19 caused by emerging variants

 Novavax has linked its COVID-19 vaccine to 100% efficacy against severe disease in countries where variants of concern are prevalent. The final phase 3 data suggest NVX-CoV2373 may protect against the worst outcomes caused by the coronavirus variants, even though the mutations limit its efficacy.

In January, Novavax shared initial results from a phase 2b clinical trial in South Africa and a phase 3 study in the U.K. The readout suggested NVX-CoV2373 is highly effective against the original coronavirus and the B.1.1.7 variant predominant in the U.K., but offers far less protection against the B.1.351 lineage that accounts for many cases in South Africa.

Final data from the two studies confirm the initial findings. In the U.K., overall vaccine efficacy came in at 89.7%. The figure breaks down into 96.4% efficacy versus the original coronavirus and 86.3% protection against B.1.1.7.

The fall-off in efficacy against B.1.351, which has the E484K escape mutation, was far steeper. With B.1.351 accounting for most cases, the vaccine achieved an overall efficacy of 48.6%. Efficacy came in at 55.4% in the cohort of HIV-negative participants. Novavax is yet to share safety data beyond a brief statement that its “vaccine is well-tolerated, with low levels of severe, serious and medically attended adverse events at day 35, balanced between vaccine and placebo groups.”

Those results hew closely to the interim findings Novavax released in January. Novavax now has more data on protection against severe disease, though, which may allay some concerns about the variants and help the biotech as it seeks authorization to sell the vaccine in the U.S.

As of the January data drop, Novavax had seen two severe cases in the placebo cohorts, one in each trial, and none in the vaccine arms. The dataset was too small to say anything about the ability of the vaccine to protect against severe disease.

Now, Novavax has 10 cases of severe COVID-19, again split evenly between the two trials. All of the cases happened in subjects who received placebo, suggesting the vaccine protects against the worst COVID-19 outcomes even when the individual is infected with B.1.1.7 or B.1.351.   

The numbers involved are still small but may be sufficient to persuade regulators that the vaccine is effective at preventing severe disease. FDA guidance states “5 or more severe COVID-19 cases in the placebo group would generally be sufficient to assess whether the severe COVID-19 case split between vaccine vs. placebo groups supports a favorable benefit-risk profile.”

Novavax has enough severe cases to fulfill that requirement but, unlike the developers of vaccines that have already received emergency use authorization, its current pivotal data come from outside of the U.S. Final data from a U.S.-Mexico phase 3 clinical trial of NVX-CoV2373 are still some way off, meaning Novavax will need to persuade the FDA to accept ex-U.S. data if it is to bring its vaccine to market in the first half of the year.

Even if Novavax secures its targeted May approval, it is plausible that most U.S. adults will have had a chance to receive a vaccine from Johnson & Johnson, Moderna or Pfizer-BioNTech by the time it gets to market. Yet, analysts at Jefferies still see a commercial opportunity for Novavax.

“There remains a debate as to whether there will be enough "high efficacy" vaccines for the rest of the world and whether NVAX can make inroads there. Moreover, the issue of a third booster dose to handle waning immunity or emerging variants still remains an outstanding question,” the analysts wrote in a note to investors. Novavax is working on new constructs against emerging variants and has a platform that may be well suited to repeat doses and multivalent vaccines. 

https://www.fiercebiotech.com/biotech/novavax-links-vaccine-to-full-protection-against-severe-covid-19-caused-by-emerging

Novartis' Sandoz, with Aubagio generic in its sights, sues FDA to launch copycat first

 Here's a hypothetical: What happens when the FDA grants exclusivity to a new drug ingredient that isn't exactly new?

Novartis' generics unit claims the agency did just that with Sanofi's multiple sclerosis med Aubagio—but the dispute isn't necessarily just about the New Chemical Entity (NCE) exclusivity itself. That's no longer in force according to the FDA Orange Book. It's also about the 180-day exclusivity drugmakers win when they're first to file for copycat approval—and right now, 20 generics are poised to hit the scene simultaneously in 2023.

Sandoz has already petitioned the agency two times, arguing that Sanofi didn't deserve NCE status for Aubagio. Now, it's suing the FDA for the "unlawful award" and for the agency's refusal to accept Sandoz's first application for a copycat version.

If the court doesn't force the FDA to accept that early app, it could cost Sandoz the coveted 180-day exclusivity, when one generic rules the market, prices are higher and competition from other copycats nil, the lawsuit claims.

The lawsuit itself says that a six-month lock on the market is worth $100 million to Sandoz. And the NCE argument is key to whether the generics unit deserves it because a generics maker can file for approval a week ahead of the typical date—if they believe an NCE wasn't properly granted, that is.

To win NCE status—essentially, to be called a brand new, innovative drug—the med's active ingredient must be new. Aubagio's active ingredient is teriflunomide—a new substance—but the molecule was known to be effective against autoimmune diseases such as MS "long before" Sanofi filed Aubagio for approval, the lawsuit claims.

The FDA itself knew this, the lawsuit states. Since 1998, Sanofi has sold a rheumatoid arthritis drug, Arava, whose active ingredient is leflunomide. That ingredient is metabolized in the body to become teriflunomide, "which is responsible for essentially all of leflunomide’s in vivo activity,” Arava's FDA label states, as cited by the lawsuit. 

FDA itself has said that teriflunomide "was well understood" by the agency ahead of Aubagio's approval and that, for all intents and purposes, the drug is "equivalent" to Arava, the lawsuit claims.

In August 2016, the company formally challenged the FDA's NCE award to Aubagio. It followed up with two Abbreviated New Drug Applications (ANDAs) for its generic version on September 7 and September 12, 2016—the date when companies were allowed to file copycats under the period of NCE exclusivity.

A slate of other generics makers did just that on September 12, 2016. And now, unless the court tells the FDA to accept Sandoz's September 7 application, it will be vying for market space alongside 20 other generic applicants when Aubagio generics launch.

Sandoz lost its first petition to the FDA. It appealed and lost again. Hence the lawsuit, which argues that the FDA's stance undermines the purpose of NCE exclusivity, which is to promote development of previously unapproved therapeutic molecules. "[T]hat, after all, is what makes them new," the lawsuit states. Instead, the FDA gave Sanofi a "windfall renewal of NCE exclusivity" for an ingredient approved years back in Arava, Sandoz claims. 

"NCE exclusivity is an important incentive for the discovery and development of new therapeutically beneficial molecules," Leslie Pott, communications VP at Sandoz, said via email. "However, where it is awarded improperly to a molecule that is not new, challenging such an award is a critical part of ensuring that affordable generic alternatives can be brought to the market in a timely manner," she continued. 

Meanwhile, Novartis' branded multiple sclerosis blockbuster, Gilenya, is set to face generic competition of its own later this decade. In December 2019, the FDA tentatively approved the first three generic versions of the drug, made by HEC Pharm, Biocon and Sun Pharmaceutical, though they won't be hitting the market immediately. In June of that same year, the U.S. Patent Office issued a ruling that protected the branded version of Gilenya until 2027.

https://www.fiercepharma.com/pharma/generic-catch-22-novartis-sandoz-sues-fda-over-sanofi-blockbuster-s-unlawful-exclusivity

FDA calls meeting to weigh quick cancer approvals, threatening Merck, Bristol, Roche

 As part of an industry-wide review, the FDA persuaded PD-1/L1 players Merck & Co., Bristol Myers Squibb, Roche and AstraZeneca to remove four indications on the labels of cancer drugs, after the failure of post-marketing studies. But the agency wasn’t so sure about six others, so it’s calling for some external input.

In what promises to be a heated deliberation, the FDA will convene experts on its oncologic drugs advisory committee to a three-day meeting in late April to discuss six indications that had been added to drug labels on an accelerated basis but that ultimately failed confirmatory trials, it said in a public notice (PDF) filed Thursday.

The expert panel will discuss data on three indications for Merck’s Keytruda, two for Roche’s Tecentriq and one for Bristol Myers’ Opdivo. The FDA doesn’t have to follow an advisory committee’s recommendation, but it typically does.

The first item on the agenda will be Tecentriq’s conditional nod in combination with Bristol Myers’ chemotherapy Abraxane in PD-L1-positive triple-negative breast cancer.

The drug earned that go-ahead based on data showing that the regimen could stave off cancer progression. But a confirmatory trial dubbed IMpassion131 found the pairing of Tecentriq with the original paclitaxel drug couldn’t extend the lives of newly diagnosed TNBC patients over solo chemo.

On the second day, the panel will discuss two front-line bladder cancer uses of Keytruda and Tecentriq in patients who are not eligible for cisplatin-based chemo. Those concerns were triggered by lackluster overall survival findings from the Keynote-361 trial for Keytruda and the IMvigor211 study in the second-line setting and IMvigor130 study in the front-line for Tecentriq.

The FDA had previously limited the use of the two drugs in front-line, cisplatin-ineligible bladder cancer to patients who met certain PD-L1 expression standards, after noticing reduced survival rates in patients with low PD-L1 levels.

The third day will focus on conditional second-line liver cancer nods for Keytruda and Opdivo, after their confirmatory trials failed. The use of Keytruda in third-line PD-L1-positive gastric or gastroesophageal junction adenocarcinoma will also be discussed, given that it flunked the Keynote-061 and Keynote-062 trials in previously treated and newly diagnosed patients.

The FDA has persuaded some drugmakers to remove indications after misses in confirmatory trials. These include Keytruda and Opdivo in previously treated small-cell lung cancer, and Tecentriq and AstraZeneca’s Imfinzi in previously treated bladder cancer.

The fact that drugmakers did not voluntarily remove the additional six indications, prompting the advisory committee meeting, indicates some amount of disagreement between the companies and the FDA. There is some precedent here: The FDA removed its approval of Roche’s Avastin in breast cancer after the drug failed to improve patients’ life span in a confirmatory trial. That landmark decision came after a heated public debate among physicians, patients, the drugmaker and the FDA, which culminated in a two-day hearing.

The FDA has long been criticized for inadequate supervision of post-marketing commitments made by drugmakers that have received accelerated conditional approvals. For example, Keytruda has remained on the market in stomach cancer for over three years, despite its first Keynote-061 flop.

The FDA’s internal review document, as well as the agency’s final ruling on the six indications the agency is about to reconsider, may offer a benchmark for drugmakers considering what to do after confirmatory trials fail.

https://www.fiercepharma.com/marketing/fda-convenes-adcom-to-review-accelerated-approvals-failed-trials-threatening-merck