JP Morgan 2023 – Novartis and Gilead's interim halt hopes wane

 As 2023 got under way investors in Novartis and Gilead might have been looking for pleasant surprises from interim analyses of two key studies. Such hopes have been dashed, according to updates slipped out at the JP Morgan healthcare conference this week. Novartis’s Kisqali is trying to break into adjuvant breast cancer, where Lilly’s rival Verzenio is approved but where Pfizer’s Ibrance failed in the Pallas trial. But Kisqali’s Natalee study is now continuing to final readout in the second half of the year, having not been halted for efficacy at its two interim analyses, which came and went at 70% and 85% of disease progressions respectively. Meanwhile, the Enhance trial of Gilead’s anti-CD47 MAb magrolimab in first-line high-risk myelodysplastic syndromes had an expected first interim analysis in the current quarter, but this too has passed without triggering a halt for efficacy. The CD47 mechanism has disappointed, and Enhance's focus now turns to a second interim analysis in the second half of the year.

Project	Kisqali	Magrolimab
Company	Novartis	Gilead (ex Forty Seven)
Trial	Natalee	Enhance
Setting	Adjuvant pre & postmenopausal HR+/Her2- breast cancer; (approved for 1st-line metastatic HR+/Her2- breast cancer)	1st-line, high-risk MDS; (also in pivotal trials for 1st-line TP53m AML (Enhance-2) & 1st-line unfit AML (Enhance-3), as well as other haem & solid cancers)
Interim analyses	1st at 70% of iDFS events (YE 2022, not halted) 2nd at 85% of iDFS events (H1 2023, not halted)	1st at unspecified threshold (H1 2023, not halted)
Status	Continues to final analysis (H2 2023), with iDFS as primary endpoint	Continues to 2nd interim analysis (H2 2023), with focus on OS (currently a co-primary endpoint along with CR rate); (NB had been on clinical hold in 2022)
Source: clinicaltrials.gov & JP Morgan presentations. https://www.evaluate.com/vantage/articles/events/conferences-snippets/jp-morgan-2023-novartis-and-gileads-interim-halt-hopes

Panbela Starts Phase II Trial of CPP-1X-T for Recent Onset Type I Diabetes

 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, today announced that it has commenced a Phase II double-blind, randomized study to evaluate CPP-1X-T (Eflornithine tablets) for recent onset type 1 diabetes, in collaboration with Indiana University School of Medicine and funded by JDRF, the leading global type 1 diabetes research and advocacy organization.

Indiana University expects to enroll 70 patients in the Phase II clinical trial at approximately 6 centers in the United States. Study eligibility will be for patients with recent onset type 1 diabetes. Participants will be randomized 2:1 to CPP-1X-T, administered orally with food, twice daily, at a 1000 mg/m2 dose, or placebo over 6 months followed by a 6 month wash out period to assess durability of response. The primary objective will be to determine the difference between the treated and placebo 2-hour Area Under the Curve (AUC)-mean using the log (mean C-peptide+1) at the 6-month end of treatment period. Secondary objectives will include C-peptide AUC, fasting and stimulated proinsulin/c-peptide ratios a biomarker of β cell stress, and the urine polyamine content at 3, 9, and 12 months timepoints.

https://finance.yahoo.com/news/panbela-starts-phase-ii-trial-140000779.html

AstraZeneca AIRSUPRA™ (PT027) approved in the US for asthma

 First and only rescue medication approved in the US for as-needed use to reduce risk of asthma exacerbations

AIRSUPRA™ (albuterol/budesonide), formerly known as PT027, has been approved in the US for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in people with asthma aged 18 years and older.

The approval by the Food and Drug Administration (FDA) was based on results from the MANDALA and DENALI Phase III trials.1,2 In MANDALA, AIRSUPRA significantly reduced the risk of severe exacerbations compared to albuterol in patients with moderate to severe asthma when used as an as-needed rescue medication in response to symptoms.1 Importantly, in the secondary endpoint of mean annualized total systemic corticosteroid exposure, AIRSUPRA demonstrated a significant reduction compared to albuterol at the approved dose of 180mcg albuterol/160mcg budesonide.1 In DENALI, AIRSUPRA significantly improved lung function compared to the individual components albuterol and budesonide in patients with mild to moderate asthma.

https://finance.yahoo.com/news/airsupra-pt027-approved-us-asthma-140000229.html

Flights 'resuming gradually' across the country following FAA system outage

 The FAA said air traffic operations are gradually resuming after flights were grounded this morning due to an outage with an important Federal Aviation Administration (FAA) system for pilots.

Earlier this morning the FAA said it was grounding all flights until 9 a.m. ET this morning in order to “validate the integrity of flight and safety information,” stemming from an outage with its Notice to Air Missions (NOTAM) system.

Per an update from the FAA, the ground stop has been lifted and "air traffic operations are resuming gradually across the United States." The FAA continues to look into the cause of the problem, the agency said.

The NOTAM system sends out flight hazards and restrictions to pilots prior to takeoff. A NOTAM bulletin can sometimes be as long as a couple hundred pages detailing issues like possible bird activity or closed runways.

Flights currently in the air are allowed to travel to their destinations, however all flights scheduled to take off were grounded.

Per the Air Traffic Control System Command Center, the NOTAM system went down around 3:28 am ET.

ABC News reported that a senior official briefed on the matter said the software issue led to a “cascading” series of IT failures, leading to this morning’s flight groundings.

As of 7:15 a.m., more than 1,200 flights had been delayed into or out of the U.S., which was shortly before the FAA announced the pause.

Airline stocks are all trading lower in the pre-market before the opening bell on Wall Street.

https://finance.yahoo.com/news/flights-resuming-gradually-across-the-country-following-faa-system-outage-134128446.html

Inotiv upped to Buy from Hold by Lake Street

 Target to $10 from $4

https://finviz.com/quote.ashx?t=NOTV&p=d

Lipelia Achieves Phase 2A Topline for Hemorrhagic Cystitis Candidate

 Lipella Pharmaceuticals Inc. (Nasdaq: "LIPO") ("Lipella," "our, "us" or the "Company"), a clinical-stage biotechnology company focused on developing new drugs by reformulating the active agents in existing generic drugs and optimizing these reformulations for new applications, today announced top line results of the Company's recently completed Phase 2a clinical trial evaluating the safety and efficacy of its drug candidate LP-10 for Hemorrhagic Cystitis, a rare but highly morbid disease for which there are currently no FDA approved treatments.

Jonathan Kaufman, Chief Executive Officer, will present a corporate overview including the top-line results, at Biotech Showcase 2023™ on Wednesday, January 11th at 2:00pm PST at the Hilton San Francisco - Union Square, 333 O'Farrell Street, San Francisco, CA.

https://finance.yahoo.com/news/lipella-pharmaceuticals-announces-successful-top-123000290.html

Lilly Gears Up for ‘Unprecedented Year,’ Touts Promising Pipeline

 Following a banner year marked by the approval and launch of its diabetes drug Mounjaro (tirzepatide), Eli Lilly revealed at the 41st J.P. Morgan Healthcare Conference that it was preparing for another big year.

In a fireside chat led by Anat Ashkenazi, Lilly’s executive vice president and chief financial officer, and Daniel M. Skovronsky, M.D., Ph.D., Lilly’s chief scientific and medical officer, the company detailed its busy year ahead, business forecasts and a robust pipeline that will support its long-term growth.

Product Launches and Pipeline Prospects

• Eli Lilly is preparing to launch four new molecules: donanemab for early Alzheimer’s disease, lebrikizumab for atopic dermatitis, mirikizumab for ulcerative colitis and pirtobrutinib for relapsed/refractory mantle cell lymphoma. All four drugs are currently under regulatory review.
• The donanemab program, in particular, is in a good position, said Skovronsky, after the success of Biogen/Eisai’s lecanemab. Lilly is eyeing accelerated approval for donanemab.
• Mounjaro (tirzepatide), approved in May 2022 for type 2 diabetes, could launch a second indication in obesity as early as the end of 2023.
  • Five more molecules are in Lilly’s development horizon: once-weekly insulin, an oral SERD molecule in phase III assessments for breast cancer, the next-generation Alzheimer’s drug remternetug, the obesity-hopeful retatrutide and the oral GLP1 receptor agonist, orforglipron.
• R&D in the early and middle stages of drug development will continue to ensure longevity for Lilly’s portfolio.
• In immunology, Lilly is flipping the checkpoint agonist technology, a common approach in cancer, to dampen the activation of the immune system. The company had recently released proof-of-concept data showing the potential of PD-1 agonists in rheumatoid arthritis.
• In cancer, several investigational molecules are being studied, including a PI3K kinase in Phase I and KRAS inhibitors.
• The company is also consistently looking for therapeutic areas that are “out of favor, largely, from the pharmaceutical industry” where Lilly can innovate, Skovronsky said.

Business Updates and Forecasts

• For 2023, the company is projecting that the core business’ top-line growth “should be in the mid-teens,” Ashkenazi said. Strong and sustained growth is expected throughout the end of the decade.
• The company is expanding its manufacturing footprint with two upcoming sites in North Carolina, one of which is expected to be operational this year. Lilly also has two new facilities in Indiana and another in Ireland.
• The company expects increased competition in the obesity market and is ready to cope through innovation. Skovronsky said Lilly is looking to bring multiple incretins to the market in the coming years to target different patient subpopulations.
• In business development, Ashkenazi said that Lilly is “not looking for a huge merger or acquisition to replace revenue.” Instead, the company will continue to improve its pipeline and bring first-in-class or best-in-class drugs into its core therapeutic areas.

https://www.biospace.com/article/lilly-gears-up-for-unprecedented-year-touts-promising-pipeline/