Prostate Cancer Metastases at Diagnosis on the Rise

Investigators have documented a sustained and definitive increase in the incidence of prostate cancer (PCa) distant metastases at diagnosis, according to a study presentation at the 2019 American Urological Association annual meeting.

The incidence of distant metastases at PCa diagnosis increased gradually from 130.1 to 157.3 per million men aged 50 to 74 years from 2007 to 2015 following a slight decline from 2005 to 2007, Neal Patel, MD, of Weill Cornell Medical College in New York, reported. The incidence increased from 451 to 586.1 per million men aged 75 years or older from 2011 to 2015 after a progressive decline from 2004 to 2011.

The incidence of distant metastases increased significantly from 451 to 504 per million men from 2011 to 2012. Among men aged 75 years or older, the incidence increased from 532.3 to 586.1 per million men from 2014 to 2015.

In contrast, from 2004 to 2015, the incidence of nonmetastatic PCa decreased from 4618 to 2977 per million among men aged 50 to 74 years and from 6919.3 to 3221.1 per million among men aged 75 years or older.

Potential causes of the risk in metastatic disease at presentation among men aged 75 years and older include an evolution in imaging for PCa staging, including the use of positron emission tomography/computed tomography, magnetic resonance imaging, and prostate-specific membrane antigen imaging as well as shifts in PSA screening, Dr Patel told attendees.

Read more of Renal & Urology News’ coverage of the AUA 2019 meeting by visiting the conference page.

Reference

Patel N, Sedrakyan A, Bianco F, et al. Definitive and sustained increase in prostate cancer metastases in the United States. Presented at the 2019 American Urological Association annual meeting held May 3-6 in Chicago. Abstract PD30-10.

Prostate Cancer Metastases at Diagnosis on the Rise

Prostate Cancer Hormone Therapy Ups Dementia Risk

Androgen deprivation therapy (ADT) for prostate cancer is associated with an increased risk of dementia, according to separate studies presented at the 2019 American Urological Association annual meeting.

In a study of 100,414 men with PCa aged 66 years or older—37,911 (38%) of whom received ADT within 6 months of diagnosis—receipt of any pharmacologic ADT, compared with no ADT, was significantly associated with a 22% increased risk of dementia from any cause, 29% increased risk of Alzheimer’s disease, and 15% increased risk of psychiatric services use, Karl Heinrich Tully, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, reported on behalf of his research team.

The investigators observed a dose-response relationship, with ADT duration of 7 months or longer significantly associated with a 30% and 41% increased risk of all-cause dementia and Alzheimer’s disease, respectively, compared with no ADT. They observed no dose-response relationship between ADT and use of psychiatric services.

The findings come from a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. The study excluded men with a prior history of stroke, dementia, or use of psychiatric services reported in Medicare claims. The cohort included men diagnosed with localized or locally advanced PCa from January 1992 to December 2009 and followed up until the administrative end of follow-up at 36 months or death.

Separately, in a population-based study of 24,464 men with newly diagnosed PCa, Ming-Chieh Kuo, MD, of Chung-Shan Medical University in Taipei City, Taiwan, and colleagues found a significant 51% increased risk of overall cognitive decline, 38% increased risk of dementia, and 83% increased risk of Parkinson’s disease among men who received ADT compared with those who did not.

The increased risk differed by ADT type. Use of oral antiandrogens was significantly associated with 70% and 54% increased risks of overall cognitive dysfunction and overall dementia, but was not associated with Alzheimer’s dementia. Combined androgen blockade was significantly associated with a 27% increased risk for overall cognitive dysfunction but not overall dementia or Alzheimer’s dementia. Luteinizing hormone-releasing hormone (LHRH) agonists and bilateral orchiectomy were not associated with cognitive dysfunction.

In addition, the investigators found that oral antiandrogens were significantly associated with a 51% increased risk of non-Alzheimer’s dementia and 6.6-fold increased risk of Parkinson’s disease, whereas LHRH agonists were not associated with either of these conditions.

Also at the meeting, South Korean investigators reported on population-based study showing that ADT for PCa was associated with cognitive dysfunction. The study, presented by Jae Young Park, MD, of Korea University College of Medicine in Ansan, included 35,410 patients with PCa identified using South Korea’s National Health Insurance Service Database. Of these, 24,567 (70.6%) underwent ADT. During a mean follow-up of 4.1 years, 4741 patients were newly diagnosed with cognitive dysfunction. ADT was associated with a significant 17% increased risk of cognitive dysfunction.

Read more of Renal & Urology News’ coverage of the AUA 2019 meeting by visiting the conference page.

References

Krasnova A, Tully KH, Epstein M, et al. Risk of dementia following androgen deprivation therapy for treatment of prostate cancer. Presented at the 2019 American Urological Association annual meeting held May 3-6 in Chicago. Abstract PD30-12.

Kuo MC, Tseng CS, Huang CY, et al. Different androgen deprivation therapies have unequally impact on cognitive dysfunction—an analysis from a population-based study using time-dependent exposure model. Presented at the 2019 American Urological Association annual meeting held May 3-6 in Chicago. Abstract PD15-02.

Sik TB, Choi H, Park JY, et al. Correlation of androgen deprivation therapy with cognitive dysfunction in patients with prostate cancer: A nationwide population-based study using the National Health Insurance Service Database.  Presented at the 2019 American Urological Association annual meeting held May 3-6 in Chicago. Abstract PD30-11.

Prostate Cancer Hormone Therapy Ups Dementia Risk

Cancer biotech NextCure sets terms for $75 million IPO

NextCure, a clinical-stage biotech developing cancer immunotherapies, announced terms for its IPO on Monday.

The Beltsville, MD-based company plans to raise $75 million by offering 5 million shares at a price range of $14 to $16. At the midpoint of the proposed range, NextCure would command a fully diluted market value of $350 million.

NextCure was founded in 2015 and plans to list on the Nasdaq under the symbol NXTC. Morgan Stanley, BofA Merrill Lynch and Piper Jaffray are the joint bookrunners on the deal. It is expected to price during the week of May 6, 2019.

Relevant Profile: NXTC

https://www.renaissancecapital.com/IPO-Center/News/62905/Cancer-biotech-NextCure-sets-terms-for-$75-million-IPO

Avantor, a supplier for the life sciences industry, sets terms for $3.0 billion IPO

Avantor, an LBO’d provider of laboratory supplies and services, announced terms for its IPO on Friday.

The Radnor, PA-based company plans to raise $3.0 billion by offering 154 million shares at a price range of $18 to $21. Insiders are offering 100 shares. At the midpoint of the proposed range, Avantor would command a fully diluted market value of $8.6 billion.

Avantor was founded in 1904 and booked $5.9 billion in sales for the 12 months ended March 31, 2019. It plans to list on the NYSE under the symbol AVTR. Goldman Sachs, J.P. Morgan, BofA Merrill Lynch, Barclays and Jefferies are the lead bookrunners on the deal; other bookrunners include Credit Suisse, Deutsche Bank, Evercore ISI, Guggenheim Securities, Morgan Stanley, UBS Investment Bank, Citi, Cowen, Piper Jaffray, and RBC Capital Markets. It is expected to price during the week of May 13, 2019.

Relevant Profile: AVTR

https://www.renaissancecapital.com/IPO-Center/News/62999/Avantor-a-supplier-for-the-life-sciences-industry-sets-terms-for-$3.0-billi

Biotech week ahead, May 6

Last week could be termed as a mixed one for the biotech sectors. Big pharma earnings came in mostly positive, but the FDA rejected two NDAs, pressuring Nabriva Therapeutics PLC – ADR NBRV and Heron Therapeutics Inc HR 1.73%.

The following are key catalysts for the unfolding week.

Conferences

• 16th International Conference on Breast Pathology and Cancer Diagnosis: May 10-11 in Montreal, Canada.
• 2019 American Academy of Neurology annual meeting: May 4-10 in Philadelphia, Pennsylvania.
• American Urological Association 2019 annual meeting: May 3-6 in Chicago, Illinois.
• Hemostasis & Thrombosis Society 2019 Scientific Symposium: May 9-11 in New Orleans, Louisiana.

Clinical Trial Readouts

American Academy of Neurology Annual Meeting Presentations

Novartis AG NVS 0.82%: Data from the Phase 3 SPRINT study for Zolgensma (pre-symptomatic patients with spinal muscular atrophy Types 1, 2 and 3 — as well Phase 1 data for Zolgensma in SMA Type 2 — on May 5.

Cytokinetics, Inc. CYTK 4.73%: Phase 2 data for Reldesemtiv in a study dubbed FORTITUDE-ALS (amyotrophic lateral sclerosis) on May 5.

MediciNova, Inc. MNOV 3.13%: additional Phase 2b data for MN-166 (progressive multiple sclerosis) on May 6.

PTC Therapeutics, Inc. PTCT 1.74% and Roche Holdings AG Basel ADR RHHBY 0.97%: Phase 2/3 data for RG7916 from a study dubbed SUNFISH (spinal muscular dystrophy) on May 7.

Ra Pharmaceuticals Inc RARX 1.17%: already released Phase 2 data for RA101495, or zilucoplan, (myasthenia gravis) on May 7.

PTC Therapeutics: Phase 2/3 data for RG7916 from a study dubbed Firefish (spinal muscular dystrophy) on May 7.

American Urological Association 2019 Annual Meeting Presentations

Urovant Sciences Ltd UROV 3.37%: already released Phase 3 data for Vibegron (overactive bladder) on May 5.

Urogen Pharma Ltd URGN 0.46%: already released Phase 3 data for MitoGel (urothelial carcinoma) on May 5.

Progenics Pharmaceuticals, Inc. PGNX 4.56%: Phase 2/3 data for PyL (prostate cancer) on May 6.

Earnings Highlights

Monday, May 6

• GW Pharmaceuticals PLC- ADR GWPH 1.44% (after the market close)
• Ultragenyx Pharmaceutical Inc RARE 4.35% (after the market close)

Tuesday, May 7

• Regeneron Pharmaceuticals Inc REGN 0.51% (before the market open)
• Jazz Pharmaceuticals PLC JAZZ 2.12% (after the market close)

Wednesday, May 8

• Portola Pharmaceuticals Inc PTLA 2.5% (before the market open)
• Dynavax Technologies Corporation DVAX 4.03% (after the market close)

Thursday, May 9

• Ionis Pharmaceuticals Inc IONS 1.69% (before the market open)
• Puma Biotechnology Inc PBYI 1.34% (after the market close)

IPOs

Applied Therapeutics, a biotech company developing therapies for diabetic cardiomyopathy, is due to offer 4 million shares in an IPO that are likely to be priced between $14 and $16. The shares are to be listed on the Nasdaq under the ticker symbol APLT.

Axcella proposes to offer 3.57 million shares in an IPO with an estimated price range of $20-$22. The biotech developing therapies and food to treat metabolic dysregulation in the liver seeks to list its shares on the Nasdaq under the ticker symbol AXLA.

Cortexyme, which develops a novel therapy for Alzheimer’s disease, is expected to offer 4.412 million shares with an estimated price range of $16-$18. The company is to list its shares on the Nasdaq under the ticker symbol CRTX.

Milestone Pharmaceuticals, a Phase 3 biotech developing therapies for heart rate conditions, plans to offer 5 million shares to be priced between $14 and $16. The shares are to be listed on the Nasdaq under the ticker symbol MIST.

NextCure is scheduled to offer 5 million shares in an IPO, to be priced in the range of $14-$16. The shares of the cancer immunotherapy company are due to be listed on the Nasdaq under the ticker symbol NXTC.

https://www.benzinga.com/general/biotech/19/05/13643589/the-week-ahead-in-biotech-conferences-clinical-trial-readouts-earnings-and-ipos

At Big Neuro Meeting, Migraine Drug Competitors to Make Oral Arguments

The first new class of migraine drugs in decades won FDA approval last year. But the companies who commercialized these new therapies and their potential competitors are already planning new, more convenient versions, taken as pills instead of injectoins just below the skin, and they will present key data in the next few days at the annual meeting of the American Academy of Neurology in Philadelphia.

The new class of migraine drugs are called calcitonin gene-related peptide (CGRP) inhibitors, named for a protein associated with the development of migraine pain. By blocking CGRP, the drugs are meant to abort migraine attacks before they start. In clinical studies, these drugs have shown a reduction in frequency but haven’t completely stopped all migraines.

Migraines affect approximately 39 million people in the US, and 1 billion worldwide, according to the Migraine Research Foundation. Triptans, the last class of migraine drugs to win FDA approval in the 1990s, are pills and injections that treat migraine pain that’s already started. There are preventative therapies, such as Botox injections and drugs prescribed off label. But these treatments don’t work well and can cause serious side effects.

The new (and more expensive) CGRP therapies are drawing more patients into this market, Jefferies analyst David Steinberg wrote in a recent research note. The first three CGRP drugs to come to market are all subcutaneous injections. Patients can dose themselves using injection pens approved for use with each drug. Erenumab (Aimovig) from Amgen(NASDAQ: AMGN), fremanezumab (Ajovy) from Teva Pharmaceutical (NYSE: TEVA), and galcanezumab (Emgality) from Eli Lilly (NYSE: LLY) will have new long-term data at AAN.

That’s important, because heavy advertising and social media campaigns are driving their demand, according to Steinberg. While doctors are reporting positive results, they also told Steinberg that the frequency of side effects such as fingers and toes turning white or blue due to blood circulation problems is also higher than what was reported in clinical trials. Side effects associated with Amgen’s drug include constipation and stomach pain. In such cases, physicians switched patients to either the Teva or Lilly drug. Long-term data should help flesh out the anecdotal picture for both efficacy and safety.

Still Experimental

Alder BioPharmaceutical (NASDAQ: ALDR) trails its CGRP rivals. The Bothell, WA, company asked the FDA in February to review its drug eptinezumab. If approved, the company plans a first quarter 2020 launch. But Alder says its drug can set itself apart by working more quickly and lasting longer because it is an infusion into the bloodstream. More of the drug is immediately available to block CGRP, CEO Bob Azelby said during a February conference call.

Infusions, which require a visit to a clinic, and injections aren’t ideal. The door is open to competition from CGRP-blocking pills. SVB Leerink analyst Marc Goodman wrote in a recent research note that the convenience of a pill and long-term safety data would be a welcome alternative to monthly injections. Allergan (NYSE: AGN) is discussing data at AAN for its two CGRP pills. Ubrogepant has been submitted for FDA review in acute migraine, which is treatment after the onset of pain. Allergan will also present Phase 2/3 data for atogepant, which was developed for migraine prevention.

More Phase 3 data for migraine pills is coming from Biohaven (NYSE: BHVN) which has been testing rimegepant in three studies for acute migraine, and from Lilly, which aims to follow its migraine-prevention drug with lasmiditan, a pill developed to treat acute migraine. The data will be closely watched. Information about the safety and efficacy of these drugs has been limited compared with the injectable preventative therapies, RBC Capital Markets analyst Brian Abrahams wrote in a recent research note.

Biohaven plans to file for FDA approval in acute migraine before June 30 and is evaluating rimegepant for migraine prevention in a Phase 3 trial. Lilly submitted lasmiditan for FDA review last November.

Other companies aim to treat migraine with new approaches to old drugs. Impel NeuroPharma has developed a medical device that it says administers an aerosolized drug deep into the nasal cavity—much deeper than typical nasal sprays can reach. In migraine, Impel is testing an inhalable version of the migraine drug dihydroergotamine. Late last year, the privately held Seattle company raised more than $67 million to support clinical trials. Impel is scheduled to present safety and cardiovascular data at AAN about its migraine treatment, which is currently in Phase 3 testing.

https://xconomy.com/national/2019/05/03/at-big-neuro-meeting-migraine-drug-competitors-to-make-oral-arguments/

Could Common Heart Meds Lower Prostate Cancer Risk?

Good news for men: That blood pressure medication you’re taking might be doing double duty, helping reduce your risk of developing prostate cancer, a new study shows.

Researchers found that a beta blocker called atenolol cut men’s risk of intermediate-grade prostate cancer about in half, compared with men not taking a beta blocker.

It also appeared to significantly reduce the risk of low-grade prostate cancer, the findings showed.

However, the effect only was found with atenolol (Tenormin). Two other beta blockers — metoprolol (Lopressor/Toprol XL) and carvedilol (Coreg) — did not appear to provide any protection against prostate cancer.

“Atenolol was the only one that was significantly associated with a protection in having a diagnosis of prostate cancer,” said co-researcher Dr. Paul Frenette. He is chairman and director of the Institute for Stem Cell and Regenerative Medicine Research at Albert Einstein College of Medicine in New York City.

Beta blockers lower blood pressure by blocking the effects of the adrenaline hormone, allowing your heart to beat more slowly and with less force, according to the Mayo Clinic. The drugs also relax blood vessels, helping them to open up and improve blood flow.

Beta blockers also have another effect, inhibiting the cells lining the inside of veins and arteries, and making it more difficult to form new blood vessels.

“You basically change the metabolism of these cells, and they cannot make new blood vessels very well,” Frenette said.

Since cancerous tumors rely on new blood vessels for sustenance, researchers theorized that beta blockers might slow or block the progression of prostate cancer.

To test their theory, the investigators looked at nearly 4,200 men who received a prostate biopsy between 2006 and 2016.

Of those men, about 670 had been taking beta blockers. The researchers compared the beta blocker they were taking against whether they had been diagnosed with prostate cancer and, if they had, how advanced their cancer was.

Atenolol might have had an effect where the others didn’t, because it possibly could linger in the prostate longer, Frenette said.

“It’s known that some drugs concentrate in the prostate. It’s possible there’s some difference of the drugs to be able to act in the prostate,” he suggested.

Men taking a beta blocker shouldn’t immediately reach out to their doctor to switch their prescription to atenolol, however. “At this point, I think it’s too early,” Frenette said. “I think it should be looked at with bigger studies to be able to confirm this is indeed an effect.”

Dr. Sam Chang, chairman of urologic surgery at Vanderbilt University Medical Center in Nashville, Tenn., agreed that it’s too soon to turn this finding into clinical action.

“Bottom line, this appears interesting,” Chang said. “Much larger epidemiological studies are going to be necessary to see if there really is a potential benefit.”

The findings were presented Friday at the American Urological Association’s annual meeting, in Chicago. Research presented at meetings is typically considered preliminary until published in a peer-reviewed journal.

The study was funded by the U.S. National Cancer Institute.

https://www.webmd.com/prostate-cancer/news/20190503/could-common-heart-meds-lower-prostate-cancer-risk#1