Novo still cannot meet Wegovy demand

 How hard is it to make semaglutide? Pretty hard, apparently. On its fourth quarter earnings calls today Novo Nordisk admitted that supply constraints are still limiting the amount of the molecule, sold as both Ozempic for diabetes and Wegovy for obesity, that it can manufacture. “We are scaling really, really rapidly,” chief executive Lars Fruergaard Jørgensen said. “Unfortunately, the demand is getting even faster.” The fact that it achieved its goal of fully relaunching Wegovy in the US at the end of last year is, therefore, something of a Pyrrhic victory. The group has shortages elsewhere too. Mr Fruergaard Jørgensen said that Novo’s rare disease sales would be down by mid single digits in 2023 as it is “running short on supplies of human growth hormone”. A new manufacturing line has not scaled up as fast as the company had hoped, meaning that “Norditropin will be out of stock in a number of markets” in the coming months; scarcity of this product was already a problem. The company denied that HGH production was a casualty of the semaglutide manufacturing push, saying that the two products are made at different facilities.

Source: company presentation.

https://www.evaluate.com/vantage/articles/news/corporate-strategy-snippets/novo-still-cannot-meet-wegovy-demand

Kras flatlines

 With another quarter of sales comes another warning that the market for Kras-mutant lung cancer might be much smaller than previously thought. Amgen last night reported fourth-quarter Lumakras sales of $71m, missing sellside consensus of $90m-plus, and showing a 5% decline versus the third quarter and 8% versus the second. US revenue has stalled, while that in the rest of the world appears to be evaporating. The group says Lumakras volume rose 12%, but the hit came from lower pricing. Investors in Mirati, whose rival Kras drug Krazati was approved in December, will be watching closely. That Lumakras, expected to sell $1.6bn in 2028 according to Evaluate Pharma sellside consensus, should have plateaued within a year of launch is concerning for Amgen, which is eager to fend off criticism over its lacklustre R&D pipeline. Fears will be amplified by disappointing 2023 guidance and the revelation that Amgen’s $28bn takeover of Horizon, which is designed to fill a revenue hole but has sparked criticism from the Democrat senator Elizabeth Warren, has now been delayed by an FTC request for more information. One pipeline hope is obesity with AMG-133, and yesterday Amgen revealed a new project, AMG-786, in phase 1.

https://www.evaluate.com/vantage/articles/news/snippets/kras-flatlines

US approval tracker: January 2023

 Last month was a tale of two Alzheimer's MAbs, with celebrations for Eisai and commiserations for Lilly. Eisai’s lecanemab, now branded Leqembi, gained an accelerated approval in Alzheimer’s patients with mild cognitive impairment or mild dementia. A day after the greenlight Eisai filed for full approval. Lilly’s donanemab, on the other hand, was knocked back, as the filing did not include enough patients with at least 12 months' exposure to the MAb. Donanemab’s confirmatory phase 3 data are due mid-year. In oncology there were a couple of approval firsts in Menarini’s oral Serd Orserdu and Lilly’s non-covalent BTK inhibitor Jaypirca. Also in oncology, Beigene’s covalent BTK inhibitor Brukinsa added chronic lymphocytic leukaemia to its label. The label includes a superiority claim over Johnson & Johnson/Abbvie’s Imbruvica on overall response rate, and Beigene is planning to submit a post-approval labelling supplement to get PFS superiority added. The latter could help take market share from Astrazeneca’s Calquence, which has only demonstrated non-inferiority to Imbruvica.

Notable first-time US approval decisions in January
Project	Company	Indication(s)	2028e SBI ($m)	Outcome
Donanemab	Lilly	Early symptomatic Alzheimer's disease	1,872*	CRL
Leqembi (lecanemab)	Eisai/Biogen	Alzheimer's disease	1,854	Approved (accelerated)
Orserdu (elacestrant)	Menarini (private)/ Radius	2L and 3L ER+/Her2- advanced/metastatic breast cancer	-	Approved (~2 weeks early)
Jaypirca (pirtobrutinib)	Eli Lilly/Loxo	Mantle cell lymphoma for patients previously treated with a BTK inhibitor	-**	Approved
Airsupra (PT027)	Astrazeneca/ Avillion	As-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in asthma pts aged 18 years and older	-	Approved in adults; CRL in children aged 4-17 (negative adcom in November)
Brenzavvy (bexagliflozin)	TheracosBio	Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes	-	Approved
*Forecast prior to CRL, **sales assigned to CLL. SBI: sales by indication. Source: Evaluate Pharma, company releases.

 

Advisory committee meetings in January
Project	Company	Indication	2028e SBI ($m)	Outcome
Rezafungin	Cidara/ Melinta/ Mundipharma	Candidemia and invasive candidiasis in adults	348	14-1 in favour, in adults with limited or no alternative treatment options (Pdufa Mar 22)
Eylea	Regeneron	Retinopathy of prematurity in preterm infants	-	No vote; discussions were around appropriate communication and labelling. No anti-VEGF treatments have been approved in the US for the indication but several are used off-label (Pdufa Feb 11)
-	-	Future Covid-19 vaccination regimens	-	Recommended that all future vaccines should be bivalent. Another meeting will take place in May/June to discuss the latest variant data and whether the current booster shots will be sufficient for the autumn
Source: Evaluate Pharma, company releases, FDA adcom calendar.

 

Supplementary and other notable approval decisions in January
Product	Company	Indication (clinical trial)	Outcome
Vonaprazan (Takecab)	Phathom	Erosive oesophagitis (Phalcon-ee)	Delayed (impurity found in commercial batches, additional stability data needed. Also affects approved H pylori indication)
Tukysa + Herceptin	Seagen	Adult patients with Her2-positive colorectal cancer who have received at least 1 prior treatment regimen for unresectable or metastatic disease (Ph2 Mountaineer)	Approved (accelerated)
Brukinsa	Beigene	Adults with CLL or SLL (Alpine, Sequoia)	Approved
Keytruda	Merck & Co	Adjuvant therapy for Stage IB (≥4 cm)-IIIA NSCLC following complete resection (Pearls/Keynote-091)	Approved
Myfembree	Pfizer/Myovant	Update to prescribing information (heavy menstrual bleeding associated with uterine fibroids) based on safety and efficacy data from the Liberty randomised withdrawal study	Approved
Rybelsus	Novo Nordisk	1L treatment option for adults with type 2 diabetes	Approved
Rykindo (risperidone for extended-release injectable suspension)	Luye Pharma	Schizophrenia in adults and as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder in adults	Approved
Vabysmo	Roche	Include two-year data from Yosemite and Rhine studies in diabetic macular oedema	Approved
Evusheld	Astrazeneca	Pre-exposure prophylaxis of Covid-19	EUA removed due to lack of efficacy against circulating variants
Acalabrutinib (generic to Astrazeneca's Calquence).	Alembic Pharms	Mantle cell lymphoma (after at least one prior therapy) and chronic lymphocytic leukaemia or small lymphocytic lymphoma	Tentative approval
Source: Evaluate Pharma, company releases. https://www.evaluate.com/vantage/articles/insights/nme-approvals-snippets/us-approval-tracker-january-2023

GSK Culls Celiac, S. aureus Candidates on FDA Decision Day for CKD Drug

 GSK has dropped both GSK3915393, an investigational celiac disease therapeutic, and GSK3878858, a Staphylococcus aureus vaccine hopeful from its clinical development roster, the company revealed Wednesday.

These pipeline changes, included in the company’s Q4 and full-year results, come the same day the FDA is expected to render a verdict regarding daprodustat for adult patients with anemia arising from chronic kidney disease (CKD).

GSK gained rights to the celiac disease drug GSK3915393 when it bought San Diego biotech Sitari Pharmaceuticals in September 2019. The drug works by inhibiting the transglutaminase 2 enzyme, which plays a central role in the pathologic response to gluten in celiac disease.

GSK initiated a Phase I trial of GSK3915393 in October 2020.

Meanwhile, GSK3878858 was designed to address the growing antibiotic resistance by targeting five antigens on the bacterium. The candidate was being assessed in a Phase I/II randomized, placebo-controlled, dose-escalation study in adults with recurrent S. aureus skin and soft tissue infections. The trial began in June 2020.

Aside from the discontinued assets, GSK reported strong growth in 2022, raking in more than $36 billion in sales, which represents a 19% growth at actual exchange rates. Much of this growth was driven the company’s specialty medicines, oncology and HIV businesses, sales of which grew by 37%, 23% and 20%, respectively.

To support its future growth, GSK will look to continue the development of 69 vaccines and immune system-based specialty medicines, 18 of which are in Phase III studies or ready for registration. This pipeline includes the company’s RSV vaccine candidate for older adults, which is awaiting regulatory review in the U.S., E.U. and Japan.

GSK Braces for FDA Decision on CKD Drug

As announced in its full-year financial results, GSK is anticipating four approvals in 2023:

• Respiratory syncytial virus vaccine for older adults. The vaccine hit the primary endpoint in a pivotal trial, showing a 94.1% reduction in severe disease.
• Jemperli (dostarlimab) in endometrial cancer
• Momelotinib in myelofibrosis
• Daprodustat in CKD

In October 2022, the Agency’s Cardiovascular and Renal Drugs Advisory Committee delivered a mixed vote on daprodustat, but leaned toward approving the drug only in CKD patients on dialysis. In particular, committee members flagged potential safety concerns, which may outweigh the candidate’s benefit in patients not on dialysis. The FDA is not required to follow the vote of the Committee, but it often does.

GSK submitted data from five studies under the Phase III ASCEND program to support daprodustat’s FDA bid. While the candidate met its primary efficacy endpoints in all trials, it also aggravated the risks of heart failure, bleeding gastric erosions, heart attack and stroke in patients who not dependent on dialysis.

https://www.biospace.com/article/gsk-culls-celiac-s-aureus-candidates-on-decision-day-for-ckd-drug/

FBI searches Biden’s Rehoboth home

 Federal investigators on Wednesday searched President Biden’s home in Rehoboth, Del., after classified documents were discovered in recent weeks at Biden’s Wilmington home and his old Washington, D.C., office.

Multiple outlets reported Wednesday morning that FBI personnel were at Biden’s home in Rehoboth Beach.

Bob Bauer, an attorney for the president, said the search was being conducted with “the President’s full support and cooperation” and was not shared in advance under standard Department of Justice (DOJ) procedures.

“Under DOJ’s standard procedures, in the interests of operational security and integrity, it sought to do this work without advance public notice, and we agreed to cooperate,” Bauer said in a statement.

“The search today is a further step in a thorough and timely DOJ process we will continue to fully support and facilitate. We will have further information at the conclusion of today’s search.”

No classified materials had previously been discovered at Biden’s Rehoboth residence.

https://thehill.com/homenews/administration/3839160-fbi-searches-bidens-rehoboth-home/

Quoin starts Netherton Syndrome trial

 Company’s Second Netherton Syndrome Clinical Study has been Cleared by FDA to Initiate Testing

All Six Target Clinical Sites are on Track to be Fully Opened by Year End

Quoin Pharmaceuticals Ltd. (NASDAQ: QNRX) (the “Company” or “Quoin”), a specialty pharmaceutical company focused on rare and orphan diseases, announces that the first patient has been dosed in its ongoing clinical trial evaluating the safety and efficacy of QRX003 as a treatment for Netherton Syndrome.

Quoin’s first clinical trial is a randomized, double blinded, vehicle-controlled study which is being conducted under a U.S. Investigational New Drug (IND) Application and is assessing two different doses of QRX003 topical lotion versus a vehicle lotion in Netherton patients. The test materials are applied once daily over a twelve-week period, to pre-designated areas of the patient’s body. Based on discussions with the U.S. Food and Drug Administration (FDA), a number of different clinical endpoints will be assessed in the study.

In October 2022, Quoin announced it plans to initiate a second study assessing its QRX003 topical lotion in Netherton patients who are currently receiving off-label treatment including systemic therapy for symptomatic relief. This second study, which has now been cleared by the FDA to initiate clinical testing, is an open-label, non-placebo controlled trial that will evaluate 10 Netherton patients over a twelve week period. The study, which will run concurrently with Quoin’s ongoing clinical trial, will be conducted at the same sites and by the same clinical investigators as the first study, thereby optimizing the potential for a rapid recruitment of patients.

https://finance.yahoo.com/news/quoin-pharmaceuticals-announces-dosing-first-133000182.html

Blue Water to Partner on Development of Novel Monkeypox and Marburg Vaccine

 Blue Water Vaccines Inc. (“BWV” or “Blue Water Vaccines” or the “Company”), a biopharmaceutical company developing transformational vaccines to address significant global health challenges, today announced a collaboration with AbVacc, Inc. (“AbVacc”) for the joint development of vaccine candidates targeting monkeypox and Marburg virus disease (“MVD”).

Both candidate vaccines will utilize BWV’s norovirus shell and protrusion (“S&P”) virus-like particle (“VLP”) platform, which allows for the presentation of multiple antigens on the surface of either the S or P particle of a norovirus backbone. BWV previously announced plans to explore a novel monkeypox vaccine candidate using this platform and under this agreement, AbVacc & BWV plan to work collaboratively to optimize the vaccine design and conduct preclinical immunogenicity and efficacy studies. In addition to monkeypox vaccine development, AbVacc will utilize its extensive expertise in MVD to develop a novel vaccine targeting Marburg virus using BWV’s VLP platform.

AbVacc, a recent spin-off of Integrated BioTherapeutics Inc. (“IBT”) developing rationally designed vaccines and monoclonal antibodies, is currently developing a monoclonal antibody for treatment of MVD, IBT-T03, with discovery and preclinical development supported by multiple government grants. In May 2021, IBT was awarded a $16.3M contract from the National Institute of Allergy and Infectious Diseases to support manufacturing and a Phase 1 clinical trial for IBT-T03H. Leveraging this background in MVD, AbVacc & BWV will seek to identify Marburg antigens to be presented within BWV’s VLP platform and optimize a potential vaccine candidate.

https://finance.yahoo.com/news/blue-water-vaccines-announces-partnership-141500690.html