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Monday, December 5, 2022

Aging U.S. Population 'a Challenge for Oncologists'

 By 2030 the entire Baby Boomer generation -- now estimated by the U.S. Census Bureau to number over 73 million people -- will be older than 65.

"This is really important for us who care for individuals with cancer because the peak incidence of cancer diagnosis is in the eighth decade of life," explained Tullika Garg, MD, MPH, a specialist in geriatric oncology at Penn State Health in Hershey, Pennsylvania, during a session at the Society of Urologic Oncology annual meeting. "It is also the second leading cause of death in people who are 85 and older."

Urologic oncologists are not going to be immune from the demographic trends, she noted, adding that the incidence of genitourinary cancers is going to increase precipitously in older adults in the next few years.

Garg emphasized that oncologists should realize that older cancer patients are going to be different from their younger counterparts -- particularly in terms of age-related conditions, as well as treatment goals and preferences -- pointing to results from the GOSAFE (Geriatric Oncology Surgical Assessment and functional rEcovery) study, which assessed 977 geriatric patients prior to undergoing cancer surgery, and found that:

  • 20% had difficulty walking
  • 10% had a history of one or more falls
  • 37% were taking more than five medications
  • 31% had decreased food intake prior to surgery
  • 66% screened positive for frailty

These conditions actually inform why geriatric cancer patients have different goals and preferences, Garg said. "They're worried how cancer treatment will impact their current geriatric conditions."

For example, she added, results from a survey of 226 patients ages 60 and older who had a limited life expectancy due to cancer, congestive heart failure, or chronic obstructive pulmonary disease showed that if the outcome from treatment was survival, but with severe functional impairment or cognitive impairment, 74.4% and 88.8% of these patients, respectively, would not choose treatment.

Quoting the late geriatric oncologist Arti Hurria, MD -- "Our patients want to know if they are treated, just how sick they are going to get, they want to know if they will be able to continue to function, and if their memory will be intact" -- Garg noted that "ultimately between the combination of geriatric conditions and goals and healthcare preferences, our goal is to balance under- and overtreatment in this population."

However, older adults are a heterogenous group, she said. "And we don't have great data on how to make these decisions, and our clinical trial data are largely based on younger, healthier patients. We have to find ways to evaluate our patients -- figure out who is fit, and then tailor care to what their needs are."

Furthermore, she pointed out that traditional pre-treatment evaluations focus on chronological age, "which we know is not a great marker of fitness."

Garg suggested that oncologists should consider adopting the concept of the Geriatric 5 Ms -- representing mind, mobility, medications, multicomplexity, and matters to me -- to help determine a patient's fitness for treatment.

"One thing I would really like to do more in my own practice -- and I think something which is really important for all of us -- is to do cognitive screening," she said. "Cognitive impairment really impacts the ability to provide good informed consent for surgery, and also impacts a patient's risk of delirium in the postoperative period."

Finally, Garg suggested that oncologists use frailty screening tools such as the Geriatric 8 questionnaire and the TUG (Timed Up & Go) test, assess patients' risks of chemotherapy toxicity with tools such as the Cancer and Aging Research Group's chemotoxicity calculator, and cultivate relationships with geriatricians.

She also advised oncologists to be mindful of ageism, and their own individual biases regarding age.

"My patients have taught me a lot about what is important to them, and they do worry about their cancer," Garg said. "Certainly they care about the other non-traditional outcomes I talked about -- but they do worry about their cancer, and our goal is to get them whatever treatment we can provide that is tailored to all of their goals and preferences."


Disclosures

Garg reported no conflicts of interest.

United Therapeutics started at Sell by Goldman

 Target $230

https://finviz.com/quote.ashx?t=UTHR&ty=c&ta=1&p=d

Protalix, Chiesi: FDA Accepts Resubmitted Biologics License Application for Fabry Disease Therapy

 Protalix BioTherapeutics, Inc. (NYSE American:PLX) (TASE:PLX), a biopharmaceutical company focused on the development, production and commercialization of recombinant therapeutic proteins produced by its proprietary ProCellEx® plant cell based protein expression system, and Chiesi Global Rare Diseases, a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people affected by rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has accepted the resubmitted Biologics License Application (BLA) for pegunigalsidase alfa (PRX-102) for the proposed treatment of adult patients with Fabry disease. Pegunigalsidase alfa is a purposefully-designed, long-acting recombinant, PEGylated, cross-linked α-galactosidase-A investigational product candidate. The FDA indicated in the BLA filing communication letter that the resubmitted BLA was considered a complete, class 2 response and set an action date of May 9, 2023, under the Prescription Drug User Fee Act (PDUFA).

https://finance.yahoo.com/news/protalix-biotherapeutics-chiesi-global-rare-115000944.html

New Nkarta data backs up natural killer approach to cancer treatment

 Harnessing the power of natural killer (NK) cells to attack cancer is as-yet an unproven strategy in oncology – but one that is garnering increased interest as clinical trials start to generate data.

One leading proponent of the approach – South San Francisco’s Nkarta – has just reported new results from an early-stage trial of one of its CAR-NK therapies that will likely add to the enthusiasm for the field.

A medium or high dose of its lead, CD19-targeting CAR-NK therapy candidate NKX19 achieved complete responses in seven out of 10 patients with relapsed or refractory non-Hodgkin lymphoma (NHL), driving their cancer into remission.

The complete responses came even though they had had extensive, aggressive disease that had progressed despite a median of four earlier lines of therapy, said Nkarta in an update on the trial, which involved patients with various forms of NHL including large B cell lymphoma, mantle cell lymphoma, follicular lymphoma and marginal zone lymphoma.

A lower dose of the CAR-NK achieved a complete response in one of four NHL patients, but there were no responses in a group of five patients with either acute lymphoblastic leukaemia or chronic lymphocytic leukaemia.

It thinks CAR-NK could be easier to tolerate than CAR-T therapies, and have the additional advantage of being an off-the-shelf therapy, doing away with the cumbersome cell harvesting, production and re-infusion process required with current CD19-targeting CAR-Ts like Novartis’ Kymriah (tisagenlecleucel), Gilead Sciences’ Yescarta (axicabtagene ciloleucel) and Bristol-Myers Squibb’s Breyanzi (lisocabtagene maraleucel).

In terms of safety, the CAR-NK was associated with some infusion-related side effects that were manageable and resolved quickly, and there were no cases of neurotoxicity, graft versus host disease (GvHD) or cytokine release syndrome (CRS) – all side effects associated with CAR-T therapies.

The new data build on an earlier readout from the study earlier this year, when a complete response was seen in three of six patients at the highest dose tested, as well as positive results with Fate Therapeutics’ CAR-NK therapy for multiple myeloma and another Nkarta CAR-NK for multiple myeloma acute myeloid leukaemia and myelodysplastic syndrome. There are still questions about the durability of the effects however, as NK cells have a limited lifespan within the body.

“NKX019 continues to demonstrate impressive single-agent activity, preliminary durability and an encouraging safety profile as an off-the-shelf, on-demand cell therapy for heavily pre-treated patients with NHL,” said Nkarta’s chief executive Paul Hastings.

The company is now moving ahead with dose expansion cohorts to explore combination and single-agent regimens in patients with large B cell lymphoma, to “address the large unmet need in patients who have received prior autologous CAR T therapy.” Those will get underway in 2024.

https://pharmaphorum.com/news/new-data-backs-up-nkarta-natural-killer-approach-to-cancer/

Novartis’ Pluvicto presents survival benefit for castration-resistant prostate cancer

 It has been announced today that Novartis’ Pluvicto (lutetium vipivotide tetraxetan) has shown statistically significant and clinically meaningful radiographic progression-free survival benefit in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC).

Prostate cancer is the most frequently diagnosed cancer in men in 112 countries. A vast majority of patients diagnosed with CRPC already present with metastases at the time of diagnosis. Those with metastatic prostate cancer have an estimated 30% chance of surviving five years.

Novartis’ open-label, multi-centre, 1:1 randomised phase 3 PSMAfore trial with Pluvicto – a prostate-specific membrane antigen – evaluated 469 participants and met the primary endpoint of radiographic progression-free survival (rPFS) in PSMA-positive mCRPC patients who have been treated with androgen-receptor pathway inhibitor (ARPI) therapy, compared to a change in ARPI.

Pluvicto becomes the first PSMA-targeted intravenous radioligand therapy – combining a targeting compound or ligand with a therapeutic radionuclide or radioactive particle (in this case, lutetium-177) – to demonstrate clinical benefit in mCRPC patients before receiving taxane-based chemotherapy.

No unexpected safety findings were observed in the PSMAfore trial and data was consistent with Pluvicto’s already established safety profile.

The news comes as Novartis continues to advance a broad portfolio of radioligand therapies for treating cancer and invests in manufacturing capacity to meet the growing global demand for treatment. It also marks the second positive read-out for Pluvicto in a phase 3 trial following the VISION study in which patients with PSMA-positive mCRPC received Pluvicto plus standard of care after being treated with ARPI and taxane-based chemotherapy.

In March 2022, based on the results of the phase VISION study, the FDA approved Pluvicto and, in August and September this year, the Medicines and Healthcare products Regulatory Agency (MHRA) and Health Canada approved Pluvicto in the United Kingdom and Canada, respectively. Furthermore, in October 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of marketing authorisation for Pluvicto.

The findings will be presented at an upcoming medical meeting and submitted to the FDA for regulatory approval in 2023.

Dr Shreeram Aradhye, president of global drug development and CMO at Novartis, said: “We look forward to discussing the data with healthcare authorities in order to bring this innovative new early treatment option to many more prostate cancer patients sooner after their diagnosis.”

Novartis’ announcement comes days after AstraZeneca and Merck & Co. revealed a new global prostate cancer awareness campaign, ‘Never Miss’ launching in the US and Canada.

Meanwhile, in late November, it was announced that the jointly Bayer and Orion Corporation-developed Nubeqa plus Androgen Deprivation Therapy (ADT) in combination with docetaxel was to be the first prostate cancer treatment to be made available by NHS England through an early national access agreement.

https://pharmaphorum.com/news/novartis-pluvicto-presents-survival-benefit-for-castration-resistant-prostate-cancer/

Boston’s struggle with obesity

 There are currently only six medical technologies approved by the FDA to help obese people lose weight, and, having bid $615m for Apollo Endosurgery last week, Boston Scientific will soon own two of them. However, last year saw the market entry of a powerful weight loss drug, Novo Nordisk’s Wegovy, and approval of another, Lilly’s Mounjaro, is in the offing.

Then there are the promising, though early, data on Amgen’s AMG 133, toplined last week and presented more fully on Saturday. Perhaps one day this too could become a competitor in this space, but Wegovy and Mounjaro are the threats Boston must face in the immediate term. 

The products are intended for different populations, with devices being reserved for patients with more severe, or drug-resistant, disease – so the pharmaceuticals will seize a much larger market than the devices. But Boston has at least bought probably the most effective of these devices, and the acquisition of these obesity products could still turn out to be a successful, if niche, play. 

Mechanical means

The first device specifically approved for weight loss in obese patients was the Lap-Band gastric band. This has changed hands repeatedly over the years, having been developed by Inamed’s Bioenterics subsidiary, which saw it approved in 2001. Inamed was bought by Allergan for $3.1bn in 2006, and Apollo bought Allergan’s obesity portfolio, including Lap-Band, in 2014 for $90m. Apollo then sold its surgical products, again including Lap-Band, four years later to Reshape Medical for just $10m up front. 

Apollo is one of four companies offering a gastric balloon. These are either placed in the stomach endoscopically or swallowed, and are then inflated either with nitrogen gas or saline. These can only be used temporarily, usually for around six months. 

But Apollo's newest device, used to create a “gastric sleeve” in a procedure in which the stomach is folded and stitched to reduce both its volume and the speed of its emptying, seems to be more effective than all the other devices. Apollo ESG allowed sham-adjusted total weight loss of 13.1% in its pivotal trial, and excess weight loss of 46.8% – better than Lap-Band. 

But Apollo ESG was only approved a few months ago, and as yet has no reimbursement. Stifel analysts say it could bring in around $64m a year from out-of-pocket payments. 

The pharmaceutical approach 

This is peanuts compared with the forecast sales of the new wave of obesity drugs. Wegovy, which allowed slightly greater weight loss than Apollo ESG if their respective pivotal trials are compared, is forecast to sell $867m next year, rising to $7.8bn in 2028, Evaluate Pharma’s sellside consensus shows. And that forecast might be higher were it not for the trouble Novo is having meeting the vast demand for the GLP-1 agonist. 

Mounjaro, Lilly’s GIP/GLP-1 co-agonist that is not yet approved for obesity, had even more spectacular results, at least with the higher two doses used in its pivotal obesity trial. With safety, too, looking better than Wegovy’s, expectations for Mounjaro are colossal. It is forecast to sell $5.3bn in obesity in 2028, according to Evaluate Pharma consensus. 

There are also high hopes for Amgen’s AMG 133, which has a different mechanism again, being a GLP-1 agonist but a GIP receptor inhibitor. It will be some years before robust, late-stage data emerge on this project, however. 

Devices are second fiddle to drug therapy already, and will fall further down the pecking order should Mounjaro reach patients. But demand for obesity therapies is so great that medical technologies will find a market, albeit a rather smaller one than the pharmaceutical interventions. It is now up to Boston to make the most of what opportunity it can find. 

Obesity in the US: devices vs drugs
CompanyDevice/drugFDA approval datePatient populationWeight loss in pivotal trial
Devices
Reshape MedicalLap-Band (gastric band)Jun 5, 2001BMI of 40+ or 35-40 with comorbiditiesMean excess weight loss of 36%*
Apollo EndosurgeryOrbera (balloon)Aug 5, 2015BMI of 30-40 IB-005 trial: sham-adj total weight loss of 6.9%
Reshape MedicalObalon (balloon)Sep 8, 2016BMI of 30-40 Smart trial: sham-adj total weight loss of 3.2%
BaronovaTransPyloric Shuttle (balloon)Apr 16, 2019BMI of 40+ or 35-40 with comorbiditiesEndobesity II trial: sham-adj total weight loss of 6.7%
Spatz MedicalSpatz3 (balloon)Oct 15, 2021BMI of 40+ or 35-40 with comorbiditiesSabo trial: sham-adj total weight loss of 11.7%
Apollo EndosurgeryApollo ESG
(creates gastric sleeve)
Jul 12, 2022BMI of 30-50 Merit trial: sham-adj total weight loss of 13.1%
The new obesity drugs
Novo NordiskWegovy (GLP-1 agonist)Jun 4, 2021BMI of 30+ or 27-30 with comorbiditiesStep-1 and -3 trials: pbo-adj total weight loss of 12.4% & 10.3%
LillyMounjaro (GLP-1/GIP agonist)Filing expected 2022?Surmount-1 trial: pbo-adj total weight loss of 17.8%
Selected old obesity drugs
Novo NordiskSaxenda (GLP-1 agonist)Dec 23, 2014BMI of 30+ or 27-30 with comorbiditiesScale trial: pbo-adj total weight loss of 5.4%
VivusQsymia (adrenoceptor agonist )Jul 17, 2012BMI of 30+ or 27-30 with comorbiditiesConquer and Equip trials: Pbo-adj total weight loss of 8.6-9.4%
*No sham group, and no total weight loss figures available. For drugs, only data for the highest dose approved, or used in the pivotal trial, is included.

https://www.evaluate.com/vantage/articles/news/deals/bostons-struggle-obesity

NYMOX: New Marketing Submission for Benign Prostatic Hyperplasia

 Nymox Pharmaceutical Corporation (NASDAQ: NYMX) (the “Company”) is pleased to announce today that a new formal submission has been made by the Company in Europe for Fexapotide Triflutate for the treatment of benign prostatic hyperplasia (BPH). The trademarked name for the product in the application is NYMOZARFEX (TM). The Marketing Authorization Application (MAA) was submitted to the Danish authorities. The Company will provide further information, including other expected submissions, when the information becomes available.

https://finance.yahoo.com/news/nymox-announces-marketing-submission-nymozarfex-143000386.html