Announces Phase 3 AVAIL Trial Missed Primary Endpoint,
Appoints
Reduces Operating Expenses to Align with Streamlined Development Programs
Revises Study-Start Guidance for IMPALA 2 Clinical Trial to Q2 2021
https://savarapharma.com/investors/press-releases/release/?id=13001
Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced that the first participants have been dosed with the Company’s modified COVID-19 vaccines, designed to address the potential need for booster vaccine candidates, in an amendment to the ongoing Phase 2 clinical study.
mRNA-1273.351 encodes for the prefusion stabilized Spike protein of the SARS-CoV-2 variant B.1.351, first identified in the Republic of South Africa, and is being assessed as a booster vaccine to increase the breadth of response to emerging variants with key-receptor-binding domains (RBD) mutations. mRNA-1273.211 is a multivalent candidate which combines mRNA-1273, Moderna’s authorized vaccine against ancestral strains, and mRNA-1273.351 in a single vaccine, designed to elicit a broad immune response as both a primary series and when administered as a boost to those who have previously received mRNA-1273.
Previously published data has shown that vaccination with the Moderna COVID-19 Vaccine produced neutralizing titers against all key variants tested, including B.1.1.7, first identified in the UK, and B.1.351, with a 6-fold reduction in neutralizing titers against B.1.351. Out of an abundance of caution, Moderna is pursuing a clinical development strategy against these emerging variants. An amendment to the Phase 2 study will enroll 60 participants previously vaccinated with mRNA-1273 to receive a single booster dose of either:
In a previous protocol amendment, Phase 2 study participants vaccinated with mRNA-1273 have been offered a single 50 µg booster dose of mRNA-1273. Dosing in this protocol extension is ongoing.
Lannett, a Philadelphia-based pharmaceutical company, said it was on track to conduct a pivotal trial—meaning critical to FDA approval—of its biosimilar insulin glargine candidate, which it hopes to launch in 2023. The company said it intends to file an investigational new drug application to the FDA later this year, which would allow it to initiate the trial early in 2022.
Glargine is a long-acting insulin. The biosimilar candidate would reference Lantus, produced by Sanofi. There are no FDA-approved insulin biosimilars on the market. Lannett is primarily a generics producer and distributor. The insulin glargine project is being handled in partnership with the HEC Group of Companies.
Lannett said it recently had a Biosimilar Biological Product Development Type 2 meeting with the FDA and followed up by submitting a protocol for the trial along with a statistical analysis plan for product development. Lannett said it has received feedback on that submission and incorporated the guidance into the pivotal trial design.
Modifications made to the trial design to comply with FDA requirements included type and size of the trial and primary and secondary end points. “The proposed pivotal trial, albeit with a larger number of proposed participants, is similar to the previously completed first human volunteer pilot study, which indicated that the Lannett/HEC insulin glargine product was biosimilar to US-approved Lantus in terms of meeting all pharmacokinetics and pharmacodynamics safety end points in the study,” Lannett said.
Short-Acting Insulin Biosimilar
In February 2021, Lannett stated that it was also working with HEC to bring a short-acting insulin aspart biosimilar to market. Insulin aspart is usually taken just before meals to control blood sugar levels in adults with type 1 and type 2 diabetes. The company said that in partnering for development of this agent, it was taking aim at a $6 billion market that includes NovoLog, a Novo Nordisk product. The long-acting market is somewhat larger: $10 billion, according to IQVIA.
“We believe the clinical program for biosimilar insulin aspart will be quite similar to the clinical program for our biosimilar insulin glargine product, which is around 1 year further along in development," Tim Crew, CEO of Lannett, said in a statement.
Three coronavirus vaccines are available for use in the U.S. Each were endorsed with little drama by the Food and Drug Administration after clearly positive results in clinical trials.
But the outlook is less clear for what could soon be the fourth vaccine up for review in the U.S., a shot developed by AstraZeneca and the University of Oxford.
AstraZeneca’s vaccine is already available in more than 50 countries after preventing COVID-19 in clinical trials. But the study data are confusing, scrambled by differences in the time between shots and a manufacturing mix-up that resulted in some participants receiving half-strength doses. As a result, it’s uncertain how to most effectively use the vaccine. More recent data also raised questions about the shot’s protection against new and emerging strains of the coronavirus.
While the vaccine appears to meet the FDA’s standards for authorization, its future in the U.S. hinges on forthcoming results from a large Phase 3 study run in the country and in South America. At one point, the U.S. had bet more on AstraZeneca’s vaccine than any other and, even with three alternatives available, could still benefit from its availability.
Data are expected soon — in an early February interview, AstraZeneca research chief Mene Pangalos had predicted results were four to six weeks away — and could provide crucial answers to the remaining questions. Here’s what to watch:
Elderly people are a particularly important group to protect from COVID-19, given they are among the most likely to suffer the worst health outcomes. Yet it’s still unclear how effectively AstraZeneca’s shot prevents disease in the elderly, despite having been first cleared for use in the U.K. in December. Just under 4% of volunteers in the three trials supporting its use were over 70 years of age, and no one over 55 received what the drugmaker once believed to be the most effective regimen, a mix of lower and higher doses.
AstraZeneca has pointed to early-stage results showing immune responses in older and younger volunteers are comparable, with fewer side effects in the elderly. Just last week, British scientists published a paper showing a single dose lowered the rate of symptomatic illness in the elderly in the U.K.
Both data points suggest the shot might protect older adults from COVID-19 equally well, but the lack of clarity has led to confusion amid the vaccine’s rollout. Though the World Health Organization and European drug regulators recommended the vaccine for adults 65 and older, health authorities in France, Germany and other countries initially refused, citing the lack of data.
The U.S. study, AstraZeneca’s largest, should provide more definitive answers. Nearly one quarter of the roughly 32,000 participants were over 65. The trial could also provide a better sense of efficacy across racial and ethnic groups, as the pharma’s U.K. results were predominantly in white males. Some 21% of the U.S. study volunteers identify as either Black or Hispanic, groups which have been more severely affected by COVID-19.
Even though AstraZeneca’s vaccine is now widely authorized, researchers still don’t know the best way to use it. And that’s because of the muddled results from the U.K. trial.
When AstraZeneca first reported data in November, it said a two-shot regimen was, on average, 70% effective at preventing COVID-19. But the company noted results were much better — 90% — for participants who had mistakenly received a half, then full dose of vaccine rather than two full doses (62%). The explanation then changed in the following months, with the drugmaker contending the shot is actually most effective when two doses are given three months apart. U.K. health authorities backed that hypothesis, advising providers to administer the second shot anywhere from four to 12 weeks after the first.
Unfortunately, the U.S. trial, which began in August, isn’t testing what AstraZeneca now believes is its best regimen. Instead, it will provide answers on the performance of two full doses given four weeks apart.
Results will likely have major implications. The emergence of virus variants that diminish vaccine potency, for example, increases the risk that a suboptimal regimen might fall short of previous results.
Yet if the four-week regimen proves very effective it could lead to FDA authorization and changes to dosing elsewhere, potentially adding to the already considerable confusion.
This question may not be cleared up, but it’s an important one given the emergence of coronavirus variants and AstraZeneca’s vaccine’s weak performance against a strain that first appeared in South Africa and has since spread elsewhere, including the U.S.
Last month, South Africa stopped the rollout of AstraZeneca’s vaccine after the shot provided “minimal protection” against mild or moderate COVID-19 caused by infection with the variant, known as B.1.351, in a clinical trial.
The small size of the study and other limitations made the findings difficult to interpret. But they nonetheless fueled doubts the shot may not be as potent as others against B.1.351. While AstraZeneca’s vaccine targets the same coronavirus spike protein as other shots do, it’s aimed at a different form of that protein.
The timing of AstraZeneca’s trial makes it more likely the results will be impacted by variants. But it's unclear if the number of COVID-19 cases from variants will be significant enough to draw any conclusions. When J&J reported its results in February, for instance, nearly all the coronavirus infections sequenced in the U.S. were by the virus’ original strain. (J&J also had trial sites in South Africa, where there were enough B.1.351 cases to conclude the shot was 64% efficacy against the variant.)
As of late February, The Centers for Disease Control and Prevention had only confirmed 22 cases of B.1.351 in the U.S., where the majority of AstraZeneca's study locations are. That means the best hope for an answer about variants may come from trial sites in South America, where a variant similar to B.1.351 has spread widely.
Days after the U.S. study began in late August, testing was halted worldwide when a vaccine recipient in AstraZeneca’s U.K. trial developed a neurological illness later confirmed to be a type of spinal inflammation called transverse myelitis.
The pause was a typical safety measure in clinical testing, a way for investigators to check whether a vaccine is doing harm before giving it to more volunteers. Drug regulators in the U.K., South Africa and elsewhere quickly cleared studies to restart in early September.
In the U.S., however, the clinical hold dragged on for almost two months, an unusually long period of time. The delay caused AstraZeneca’s vaccine to fall well behind other programs and suggested the FDA had deeper concerns during its investigation.
Testing finally resumed in late October after the FDA didn’t find a link between the vaccine and that case, or an earlier, unexplained illness to a different volunteer.
AstraZeneca hasn’t had to stop its trials again since; side effects to date in clinical studies and real-world use have been mostly mild to moderate in nature. But the details surrounding the investigation should emerge in briefing documents if and when AstraZeneca seeks emergency clearance of the vaccine in the U.S.
https://www.biopharmadive.com/news/astrazeneca-oxford-coronavirus-vaccine-preview-us-results/596285/
Investors have long been concerned about the future of Bayer’s pharma franchise, given the upcoming patent cliff facing its bread and butter—heart drug Xarelto and eye med Eylea.
Now the German conglomerate is providing a first look at life after those patent expirations, which are expected around 2023. And it looks better than analysts expected it would.
Bayer expects a low- to mid-single-digit percentage sales decline for its pharma division in 2024, followed by an immediate return to growth in 2025, the company said at an investor event Wednesday. Before that, it expects annual sales growth of 3% to 5% through 2023, after adjusting for portfolio and currency changes.
As Bayer’s pharma chief Stefan Oelrich noted during his presentation, those numbers were sunnier than Wall Street’s projections. The consensus was that Bayer’s pharma sales would grow 2% through 2023, and fall 5% in 2024, according to Bernstein.
So what accounts Bayer’s optimism?
Between 2020 and 2027 period, Bayer projected a €3 billion sales decline driven mostly by Xarelto. Eylea’s sales decline should be modest by comparison and compensated by growth from Bayer’s line of contraceptive devices, as well as its cancer drugs Stivarga and Xofigo, Oelrich said.
In the meantime, Bayer hopes new launches could add €4 billion to the mix. These include prostate cancer drug Nubeqa, tumor-agnostic therapy Vitrakvi, the Merck-partnered heart failure med Verquvo and investigational heart therapy finerenone. The company also included in its calculation a risk-adjusted contribution from newly acquired menopause remedy elinzanetant and BAY1817080, a P2X3 receptor antagonist for chronic cough.
Oelrich added that additional sales could come from gene therapy licensing income generated by AskBio, which Bayer acquired last year. AskBio’s CDMO business will also help, he said.
Bayer has invested heavily in cell and gene therapy with its acquisitions of AskBio and BlueRock Therapeutics. “We expect the full value of the cell and gene therapy platform to crystalize” beyond 2027, just as the sales decline from Xarelto bottoms out, Oelrich said.
Managing the Xarelto and Eylea declines will be a challenging task for Bayer, Oelrich acknowledged. The company markets the meds outside the U.S., and it also recognizes licensing revenue on Xarelto from Johnson & Johnson in the U.S. In 2020, the drugs brought in combined sales of €6.98 billion, accounting for 40% of the pharma unit’s total haul.
For Eylea, Bayer expects “more moderate genericization dynamics given that it’s a biological product,” especially for its ex-U.S. markets, Oelrich said. The drug lost patent protection in China in 2020, and it’s set for a loss-of-exclusivity in major EU markets and Japan between now and 2025.
Bayer is still counting on Eylea to show some growth and maintain a “leading market position” for a while, driven by continued generation of real-world evidence and its extended dosing schedule, Oelrich said. Roche and Novartis’ rival drug Lucentis has long lagged Eylea in sales, and Novartis’ newly launched follow-on therapy Beovu doesn’t look like much of a threat after a safety scare that the Swiss pharma is still trying to fully understand.
Xarelto, an oral blood thinner, is facing a generic threat in China, and the product will lose its patent protection over the next several years across other major markets, Oelrich noted.
Only 11% of Xarelto revenue comes from U.S. license payments, while European sales contribute more than half of the total haul. Oelrich stressed that sales distribution is an important factor when assessing the impact of the loss of exclusivity for Xalreto.
“Historic genericization pattern of other small molecules revealed that post-patent expiry sales are decreasing [moderately] over time in many parts of Europe and in many emerging markets as well, while in the U.S. the sales decline can be very pronounced,” Oelrich said. Therefore, Bayer expects a “staggered impact” from Xalreto with a top-line “trough” in 2024, he added.
Reality star Khloe Kardashian’s appearance on "The View" talk show earned Biohaven Pharmaceuticals loads of media impressions and mentions last summer—but now it's earned the pharma company an FDA slapdown.
Kardashian appeared on the morning talk show last July just after she signed on as a Nurtec spokescelebrity. During the seven-minute segment, she talked about her daughter, her family’s reality series and her migraine headaches.
All fine so far. But she also called Nurtec ODT a “game changer,” claimed it works in 15-20 minutes and said it doesn’t give her rebound headaches like the other migraine meds she’s used. All while being recognized as a paid spokesperson for Biohaven and Nurtec.
Kardashian’s claims are false or misleading on efficacy and on risks, the FDA's Office of Prescription Drug Promotion (OPDP) wrote in the untitled letter issued Tuesday.
Biohaven acknowledged the FDA letter in a statement and added it is "working closely with the FDA to evaluate and respond.”
Along with Kardashian’s casual superlatives overstating efficacy, the OPDP pointed out that risk information is mostly missing from the segment. While the audio and video highlight Kardashian’s benefit claims, the risks are reduced to text only and in a small font size.
Instead of the typical laundry list of potential risks in TV ads, "The View" interview ends simply with host Whoopi Goldberg thanking Kardashian for being on the show to talk about migraine, asks her to repeat the drug name once more and then ends the segment saying, “We’ll be right back.” The segment is still available on the show's YouTube channel.
The untitled letter maintains that “the overall effect of disclosing risk information in this manner undermines the communication of risk information and thereby misleadingly minimizes the risks associated with the use of Nurtec ODT."
The watchdog further dinged Nurtec for failing to file the required Form FDA-2253 before the segment aired. The form and promotion submission is a required FDA filing for any drug advertising or promotion before its use. The OPDP said it reviewed the video interview on its own but also received one complaint through the FDA’s Bad Ad snitch program.
Khloe Kardashian joins sister Kim Kardashian in the bad ad doghouse in what's likely a first for family members receiving FDA promo reprimands. Kim was warned back in 2015 when she served as a spokesperson for Duchesnay morning sickness drug Diclegis. She posted an Instagram rave without an #ad label and with few risk details, but included a link to the drug’s website. Her post was captioned “OMG. Have you heard about this?” The FDA forced Duchesnay and Kim Kardashian to run another post listing all the risks.
The FDA did not delineate what if any action it may require Biohaven to take, only warning the pharma that it has 15 days to detail its response and explain its plans to discontinue the video’s use.
Khloe Kardashian, a social media star with more than 133 million followers on Instagram, signed on as a Biohaven Nurtec ambassador in July—and "The View" was one stop on her media day introductory tour. Khloe is currently featured in Nurtec branded TV ads running nationally and on the Nurtec website as part of Biohaven’s “Take Back Today” campaign.
AVEO Oncology (Nasdaq: AVEO) today announced that the U.S. Food and Drug Administration (FDA) has approved FOTIVDA® (tivozanib) for the treatment of adults with relapsed or refractory advanced renal cell carcinoma (RCC) who have received two or more prior systemic therapies. FOTIVDA is an oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI).
