Top-line phase 2 data evaluating drug candidates for treating the rare disease phenylketonuria (PKU) was announced this morning. The study compared the efficacy of 2 strains of a non-systemically absorbed drug candidate in patients with the diagnosis.
While both strains, SYNB1618 and SYNB1934, demonstrated clinically meaningful reductions in fasting plasma phenylalanine (Phe) levels, SYNB1934 will be the candidate investigated in the anticipated 2023 phase 3 clinical trial.
The rare inherited disorder is caused by a disruption in the phenylalanine hydroxylase (PAH) gene, which helps create the enzyme necessary to break down phenylalanine. As a result the phenylalanine amino acid accumulates in the body which can be dangerous and lead to serious health problems.
These patients can experience intellectual limitations in areas of thinking, understanding and communicating as well as other major health problems.Early intervention is crucialscreening for this disease is typically done at birth.
At this time there's no cure, so patients with the condition are instructed to restrict their diet to avoid foods that can increase the phenylalanine build up, typically found in high-protein foods. However, some individuals can be less restrictive if they're taking medications that are effective for them.
PKU continues to be a very challenging disease for patients, with many in need of new treatment options, Jerry Vockley, MD, PhD, Professor of Human Genetics,University of Pittsburgh, and lead investigator on the phase 2 Synpheny-1 study said in a statement. It is very promising to see these results and the potential benefits of a new, orally administered investigational product that can meaningfully lower Phe in patients with PKU.
The Synpheny-1 study was a phase 2, open-label, 28-day clinical trial that assessed the safety, tolerability and efficacy of SYNB1618 and SYNB1934 in 20 adult patients with phenylketonuria. The primary endpoint was the change in area under the curve (AUC) of plasma levels of labeled D5-phenylalanine (D5-Phe) following a meal challenge before and after the treatment period. Investigators carefully managed the patients' dietary intake to replicate their routine protein and Phe consumption.
Each candidate's ability to mitigate Phe properly was examined as the administered dose regimen was increased over 15 days of treatment and then stayed consistent at a dose of 1x1012live cells for the second half of the treatment period. Secondary endpoints included change in fasting levels of plasma Phe from baseline, incidence of treatment-emergent adverse events (TEAEs), and the levels of additional strain-specific metabolites plasma D5-TCA and urinary D5-5A.
Patients enrolled in the study had a Phe level above 600 mol/L at screening despite treatment with diet and/or sapropterin. A total of 11 patients were included in the SYNB1618 arm and with 9 in the SYNB1934 arm. At the conclusion of the investigation, 10 patients completed the SYNB1618 arm and 5 patients completed the SYNB1934 arm.
The mean change from baseline at day 14 in fasting plasma Phe was -20% for those in SYNB1618 treatment and -34% for SYNB1934. Of the patients who completed the trial, 60% had a response greater than 20% Phe reduction by day 7 or day 14, with 6 of the 10 patients dosed with SYNB1618 and 3 of the 5 dosed with SYNB1934 meeting the criteria.
No serious adverse events were reported and the mild-moderate adverse events were predominantly gastrointestinal.
The robust plasma Phe reduction demonstrated by SYNB1934 indicates that it has potential to be a transformative treatment for patients with PKU,Aoife Brennan, MB, ChB,Synlogic President, Chief Executive Officer stated. I would like to thank the patients, clinicians and staff of our investigational sites who made this study possible. We look forward to further collaboration as we initiate our Phase 3 pivotal study, with the goal of bringing this potentially life-changing innovation in the treatment of PKU to patients.
Developing company Synlogichas confirmed these data supported the decision to continue with SYNB1934 as the drug candidate advancing to a phase 3 pivotal study which is expected to begin in the first half of 2023.
Read more here:
New Rare Disease Therapy Effectively Lowers Plasma Phe in Patients with PKU - MD Magazine
- June 11th At Westport, CT: Federal Red Flags, HIPAA Security Rules and Fraud Prevention - November 7th, 2009 [November 7th, 2009]
- Do not learn Dvorak! - November 7th, 2009 [November 7th, 2009]
- You Can’t Solve Problems By Making It Illegal To Have The Problem - November 7th, 2009 [November 7th, 2009]
- A Force Fix for Healthcare - November 7th, 2009 [November 7th, 2009]
- Yahble, HIT, Bubblecon, BIZDEV!, Solid State - November 7th, 2009 [November 7th, 2009]
- 15 things that suck about the Palm Pre - November 7th, 2009 [November 7th, 2009]
- What an Indie Genomics Lab Looks Like - November 7th, 2009 [November 7th, 2009]
- Practice Fusion: Class D Felony? - February 26th, 2010 [February 26th, 2010]
- Practice Fusion Responds - March 7th, 2010 [March 7th, 2010]
- Practice Fusion: Do the math: $44,000 is a LIE - March 10th, 2010 [March 10th, 2010]
- How Much Until Doctors Approve of 23andMe? - March 10th, 2010 [March 10th, 2010]
- Biochemicals as Media, Not Methods - March 10th, 2010 [March 10th, 2010]
- More Practice Fusion Reality Distortion - March 10th, 2010 [March 10th, 2010]
- Same Test Results: 23andMe is Myriad is BRCA is Medicine - March 12th, 2010 [March 12th, 2010]
- BRCA is 23andMe is Myriad is Medicine - March 13th, 2010 [March 13th, 2010]
- Getting Serious About Genomics as Common Medical Practice - March 15th, 2010 [March 15th, 2010]
- The New John Mackey of Genetics: Linda Avey? - March 15th, 2010 [March 15th, 2010]
- Keep the Medical, Well, Medical - March 16th, 2010 [March 16th, 2010]
- If 23andMe shuts down, it won’t be for some mundane reason like the bills weren’t paid - March 16th, 2010 [March 16th, 2010]
- If I Run A Medical Practice, How Do I Use A 23andMe? - March 17th, 2010 [March 17th, 2010]
- 23andMe Contract in Bad Faith - March 19th, 2010 [March 19th, 2010]
- Doctors CANNOT Use 23andMe Due To 23andMe’s Bad Faith Contract - March 20th, 2010 [March 20th, 2010]
- Pathway Compared to 23andMe and Navigenics - March 22nd, 2010 [March 22nd, 2010]
- There’s a Word for “Views Differ” When One View Is The State - March 24th, 2010 [March 24th, 2010]
- Association for Molecular Pathology, et al. v. USPTO, et al. – Opinion - March 29th, 2010 [March 29th, 2010]
- Birth of a Super Villain - April 3rd, 2010 [April 3rd, 2010]
- “Medical Products” like 23andMe must not become the new “Financial Products” - April 4th, 2010 [April 4th, 2010]
- How I Would Apply Genomic Technology In Clinical Use Today - April 5th, 2010 [April 5th, 2010]
- Gmail Enterprise: World’s Best EMR - April 6th, 2010 [April 6th, 2010]
- Brief Primer on Health Law Compliance - April 9th, 2010 [April 9th, 2010]
- Spoiler: You ARE the “Valids” - April 9th, 2010 [April 9th, 2010]
- Rachel Lehmann-Haupt Line by Line Take Down - April 9th, 2010 [April 9th, 2010]
- Is Medicare Bankrupt? What the Hell Is Going On? - April 17th, 2010 [April 17th, 2010]
- The Big Shuffle: Medicare Cuts Rates by 21.3% (but not “technically”) - April 17th, 2010 [April 17th, 2010]
- “Tech Hiring Binge” == “Fear for Your Job, Nerds” - April 18th, 2010 [April 18th, 2010]
- How Bad is Bad? $.20 on the Private Medical Insurance Dollar - April 20th, 2010 [April 20th, 2010]
- Update: How Bad is Bad? It Used to Be $.45 on the Medical Insurance Dollar - April 20th, 2010 [April 20th, 2010]
- World’s Best “EMR” for $1000: Google Spreadsheets + iPad - April 21st, 2010 [April 21st, 2010]
- Don’t Insult Me with your “AOL Keyword” Strategy, Google Health - April 21st, 2010 [April 21st, 2010]
- How to Play LAWGAMES - April 23rd, 2010 [April 23rd, 2010]
- Top 4 Predatory Schemes Encroaching on American Medicine: Part 1 - April 25th, 2010 [April 25th, 2010]
- What’s the Big Deal About iPads? - April 27th, 2010 [April 27th, 2010]
- Got Google Android for Google I/O - April 27th, 2010 [April 27th, 2010]
- Google Enterprise meets HIPAA and HITECH Compliant Laws - April 29th, 2010 [April 29th, 2010]
- Pixels of Accuracy CHALENGE: Diagnostic Medical Imaging - April 29th, 2010 [April 29th, 2010]
- 23andMe Launder AlioGenetics Doesn’t Even Bother to Remove 23andMe Logo - April 30th, 2010 [April 30th, 2010]
- Anthem of CT Denies $600 Until “Subscriber Responds to our Coordination of Benefits Questionnaire” - May 1st, 2010 [May 1st, 2010]
- Apple And Google Team Up To Launch Revolutionary Mobile Health System - May 1st, 2010 [May 1st, 2010]
- Funny Pictures from This Year Building the Medical Practice - May 6th, 2010 [May 6th, 2010]
- Remote Medical Video Monitoring on iPad and iPhone - May 7th, 2010 [May 7th, 2010]
- Google Calendar Overhead Waiting Room Display - May 7th, 2010 [May 7th, 2010]
- Various Whiteboards on Solid State Medical Operations - May 7th, 2010 [May 7th, 2010]
- The Raw Facts about Counsyl - May 7th, 2010 [May 7th, 2010]
- Brawndo: Still Mutilating Thirst, Still Not Yet Sold at the Stop-n-Shop Pharmacy - May 9th, 2010 [May 9th, 2010]
- Video: Google Enterprise to Outsource Medical Administration - May 9th, 2010 [May 9th, 2010]
- Gattaca: “The Matrix” of Genomics - May 11th, 2010 [May 11th, 2010]
- 23andMe Now Diagnoses Fatal Tay-Sachs Disease - May 12th, 2010 [May 12th, 2010]
- Why Was Pathway Targeted for FDA Enforcement and Not 23andMe? - May 15th, 2010 [May 15th, 2010]
- John Dolan on Aging and the Horrifying Conclusion of GWAS - May 16th, 2010 [May 16th, 2010]
- Sam R. Riley Wants To Tell You About Practice Fusion - May 17th, 2010 [May 17th, 2010]
- Response to “Genomic Medicine: Lost” - May 19th, 2010 [May 19th, 2010]
- Death And Taxes: CMS to IRS - May 19th, 2010 [May 19th, 2010]
- Please Stop Antagonizing the AMA - May 26th, 2010 [May 26th, 2010]
- Dan Vorhaus, Attorney At Law, Legally Advises Medical Doctors Can Use 23andMe To Provide Medical Advice - May 28th, 2010 [May 28th, 2010]
- Singularity Summit 2010 in San Francisco to Explore Intelligence Augmentation - June 7th, 2010 [June 7th, 2010]
- OpenPCR: DNA amplification for anyone - June 10th, 2010 [June 10th, 2010]
- FDA sends letters to 5 genetic testing companies - June 11th, 2010 [June 11th, 2010]
- Amazon And The NIH Team Up To Put Human Genome In The Cloud - March 31st, 2012 [March 31st, 2012]
- ReproSource Comments on New Study Linking Infertility to Genetics - April 25th, 2012 [April 25th, 2012]
- Genetics 101 Part 1: What are genes? - Video - April 30th, 2012 [April 30th, 2012]
- Red Ice Radio - David Icke - Hour 1 - The Manipulation of Humanity - Video - April 30th, 2012 [April 30th, 2012]
- Genetics Part 5: Human Genetic Disorders - Video - April 30th, 2012 [April 30th, 2012]
- C2CAM - The Nephilim, Genetic Manipulation - April 30th, 2012 [April 30th, 2012]
- Human Nature talk with Robert Sapolsky, Gabor Mate, James Gilligan, Richard Wilkinson - Video - April 30th, 2012 [April 30th, 2012]
- Human Genetic Diseases - Video - April 30th, 2012 [April 30th, 2012]
- Alien Scientist on Genetics, Implants - April 30th, 2012 [April 30th, 2012]
- Research and Markets: Genetics, 6th Edition International Student Version Continues To Educate Today's Students for ... - May 4th, 2012 [May 4th, 2012]
- Myriad Genetics to Present at the Bank of America Merrill Lynch 2012 Health Care Conference - May 4th, 2012 [May 4th, 2012]
- Genetics may explain some people's dislike of meat - May 4th, 2012 [May 4th, 2012]
- 'Blond Genes' May Vary Around the World - May 4th, 2012 [May 4th, 2012]