CAMBRIDGE, Mass.–(BUSINESS WIRE)–AVROBIO, Inc. (Nasdaq: AVRO), a number one clinical-stage gene remedy firm with a mission to free individuals from a lifetime of genetic illness, in the present day introduced a 100% discount, or full clearance, of poisonous substrate within the kidney biopsy of the primary affected person dosed with the plato® gene remedy platform within the ongoing Section 2 FAB-GTi scientific trial of AVR-RD-01, an investigational ex vivo lentiviral gene remedy for Fabry illness. Kidney substrate discount is the trial’s major efficacy endpoint and has beforehand been utilized by the U.S. Meals and Drug Administration (FDA) in evaluating and approving remedies for Fabry illness.
The corporate additionally introduced six-month knowledge from the primary affected person dosed within the Section 1/2 trial of AVR-RD-02, an investigational ex vivo lentiviral gene remedy for Gaucher illness kind 1, displaying plasma chitotriosidase and the poisonous metabolite lyso-Gb1 – key biomarkers of Gaucher illness – had each dropped sharply under the affected person’s baseline ranges achieved on enzyme substitute remedy (ERT) earlier than gene remedy was administered. Moreover, all three cystinosis sufferers within the investigator-sponsored Section 1/2 trialii of AVR-RD-04 present sturdy knowledge throughout a number of measures and stay off cysteamine tablets and eye drops, with trial enrollment completion anticipated this yr.
“We’re thrilled to start the brand new yr with this replace, which provides to the breadth of sturdy scientific knowledge we’ve reported throughout our main lysosomal dysfunction pipeline of single-dose gene therapies,” stated Geoff MacKay, president and CEO of AVROBIO. “With 13 sufferers dosed throughout three scientific applications, now we have noticed sustained and probably transformative enhancements in key biomarkers and purposeful metrics, with knowledge from our Fabry illness program out 3 ½ years after dosing. Moreover, enrollment actions for our Fabry illness trial are accelerating, giving us added confidence in our efforts to fulfill our aim of getting dosed a cumulative 30 sufferers throughout all our scientific applications by the tip of the yr. With this sturdy momentum, we look ahead to clarifying the regulatory pathway with regulatory businesses.”
The information might be offered this week on the 17th annual WORLDSymposium™, an annual scientific assembly devoted to lysosomal problems, held just about Feb. 8-12, 2021. The displays and posters can be found on-line for WORLD attendees on the conference website.
FAB-GT biopsy knowledge: 100% discount of kidney substrate at 12 months in first affected person dosed with plato® gene remedy platform
Gb3 is a fatty substrate that accumulates within the cells of Fabry illness sufferers and can lead to harm to a number of organs, together with the kidneys, coronary heart and CNS. The kidney biopsy for Affected person 4 within the Section 2 trial confirmed a discount from a mean of 4.0 globotriaosylceramide (Gb3) inclusions per peritubular capillary (PTC) at baseline to zero inclusions per PTC one yr after dosing, a 100% discount (p<0.0001). This evaluation was made by two blinded pathologists who independently scored 99 digital pictures of the sectioned kidney from the 12-month biopsy. Each picture scored zero inclusions.
Affected person 4 is the primary within the trial handled utilizing AVROBIO’s proprietary plato® gene remedy platform, which features a state-of-the-art lentiviral vector, a customized conditioning routine with precision dosing and an automatic, closed manufacturing course of supposed to ship potent and constant drug product from manufacturing websites worldwide at industrial scale.
“The whole clearance of Gb3 substrate in kidney tissue, approaching prime of sturdy outcomes from the primary evaluable kidney biopsy on this trial, may be very thrilling,” stated Mark Thomas, M.D., the lead investigator within the FAB-GT trial, a clinician within the division of nephrology at Royal Perth Hospital and a scientific professor on the College of Western Australia Medical Faculty. “Together with the discount in plasma lyso-Gb3 noticed throughout sufferers on this trial, which has been sustained as much as 2.5 years to this point, an enormous drop in kidney substrate has the potential to considerably enhance outcomes over ERT – the present commonplace of care. Fabry illness is a severe and life-shortening situation for a lot of sufferers that requires lifelong fortnightly ERT infusions, with life-limiting signs manifesting all through the physique and mind, and we urgently want choices to halt, forestall or reverse development of the illness.”
Two of 4 FAB-GT trial contributors had evaluable kidney biopsies. As beforehand reported, the kidney biopsy for Affected person 1 confirmed an 87% discount, efficient clearance of Gb3 inclusions per PTC in comparison with baseline.
Extra Fabry illness scientific knowledge: Continued sturdiness throughout a number of biomarkers and purposeful cardiac measurements
Along with the kidney biopsy, AVROBIO reported up to date knowledge suggesting typically secure and sustained plasma and leukocyte alpha-galactosidase A (AGA) enzyme exercise and a corresponding discount in poisonous plasma lyso-Gb3 in sufferers throughout the Section 1 and FAB-GT trials of AVR-RD-01. To this point, 4 sufferers have been dosed within the Section 2 FAB-GT trial and 5 sufferers have been dosed within the absolutely enrolled Section 1 trial.
New aggregated knowledge throughout all cardiac measures for the FAB-GT sufferers present sufferers proceed to exhibit secure cardiac construction and performance at 12 months post-gene remedy, which is notable given that individuals dwelling with Fabry illness typically expertise progressive left ventricular hypertrophy and fibrosis, resulting in decreased cardiac operate.
Moreover, the corporate is leveraging current trial websites to probably develop the pool of sufferers globally, with 4 Fabry illness sufferers from Brazil at the moment shifting by means of the journey, screening, consent and enrollment course of for potential therapy at AVROBIO’s world heart of excellence in Australia.
No surprising security occasions have been recognized within the AVR-RD-01 Section 1 and Section 2 trials as of the security knowledge closing date of Nov. 26, 2020 and Dec. 7, 2020, respectively. Eight severe antagonistic occasions (SAEs) reported within the two Fabry illness trials have been in step with the conditioning routine, stem cell mobilization, underlying illness or pre-existing situations. All SAEs have been resolved with out scientific sequelae.
Enrollment within the FAB-GT trial (NCT03454893) is ongoing, and additional particulars can be found on clinicaltrials.gov.
Gaucher illness kind 1: Preliminary scientific knowledge in first affected person present enchancment in related biomarkers, plasma chitotriosidase and lyso-Gb1, over affected person’s ERT baseline
The primary affected person dosed within the Section 1/2 Guard1 trial of AVR-RD-02 exhibits substantial enchancment over pre-gene remedy ERT baseline in key biomarkers at six months post-gene remedy. This affected person, who was beforehand ERT-stable, discontinued ERT use previous to gene remedy and stays off ERT. She was handled utilizing AVROBIO’s proprietary plato® gene remedy platform.
The affected person’s plasma chitotriosidase ranges dropped 49% from her pre-gene remedy ERT baseline ranges. Plasma chitotriosidase is a biomarker of activated macrophages, which result in persistent irritation and extreme organ harm. Six-month knowledge present continued discount in plasma chitotriosidase for the reason that affected person’s three-month examination, suggesting that wholesome macrophages carrying the therapeutic gene could also be changing the diseased Gaucher cells.
At six months post-gene remedy, the affected person’s glucosylsphingosine (lyso-Gb1) metabolite ranges have been down 44% from her pre-gene remedy ERT baseline ranges. As with chitotriosidase, the lyso-Gb1 ranges have been decrease at six months than three months, suggesting continued enchancment since dosing. Lyso-Gb1 is a poisonous metabolite and a extremely delicate and particular biomarker for Gaucher illness. Elevated Lyso-Gb1 ranges contribute to the extreme organ harm generally seen in Gaucher illness.
Hemoglobin and platelet counts, that are usually low in sufferers with Gaucher illness, remained within the regular vary for the primary affected person at six months post-gene remedy.
“The early knowledge from the primary affected person dosed with AVR-RD-02, our investigational gene remedy for Gaucher illness kind 1, are in step with what now we have seen in our Fabry illness trials with lyso-Gb3,” stated MacKay. “Primarily based on the info noticed up to now, we imagine lentiviral gene remedy drives down poisonous metabolites under ranges of ERT, supporting our view that gene remedy has the potential to forestall, halt and even reverse development of those devastating illnesses with a single infusion.”
No surprising security occasions have been recognized on this first affected person. There have been no SAEs associated to AVR-RD-02 as of the security knowledge closing date of Jan. 4, 2021. Hostile occasions (AEs) reported have been in step with the conditioning routine, stem cell mobilization, underlying illness or pre-existing situations.
Enrollment within the Section 1/2 Guard1 trial (NCT04145037) is ongoing, and additional particulars can be found on clinicaltrials.gov.
Cystinosis: Continued constructive knowledge throughout a number of measures; all three sufferers stay cysteamine-independent post-gene remedy
All three cystinosis sufferers within the investigator-sponsored Section 1/2 trial of AVR-RD-04 present sturdy knowledge throughout a number of measures. Vector copy quantity (VCN/dg) knowledge for all three sufferers proceed to carry out as anticipated. The primary affected person has probably reached a VCN plateau, much like the sample seen in AVROBIO’s Fabry trials. The second affected person had a VCN of 1.7/dg at six months and the third affected person had a VCN of two.6/dg at one month. All three sufferers stay off cysteamine tablets and eye drops at 16, six and two months post-gene remedy respectively.
The renal operate knowledge for the primary affected person dosed within the trial, who has established, progressive kidney illness, recommend continued stabilization post-gene remedy. Moreover, imaging scans present a marked discount in crystal density in each corneas, in addition to a two-grade clinically significant enchancment (from grade 3 to grade 1) in his photophobia, one of many extra debilitating results of cystinosis. Photophobia may be extraordinarily painful for sufferers uncovered to any stage of sunshine, requiring some sufferers to put on darkish glasses on a regular basis, even at night time.
The investigator-sponsored Section 1/2 trial (NCT03897361) of AVR-RD-04 is predicted to be absolutely enrolled this yr. Additional particulars can be found on clinicaltrials.gov.
No surprising security occasions have been recognized within the trial, with no SAEs reported as of the Jan. 27, 2021, security knowledge closing date. AEs reported have been in step with the conditioning routine, stem cell mobilization, underlying illness or pre-existing situations.
Investor and analyst presentation in the present day at 8 a.m. ET
The convention name and presentation will start at 8:00 a.m. ET and may be accessed below “Occasions and Displays” within the Traders part of the corporate’s web site at avrobio.com or by dialing (866) 353-0165 from areas within the U.S. and (409) 217-8080 from outdoors the U.S. The convention ID quantity is 3287052. An archived webcast recording of the occasion might be obtainable on the web site for roughly 30 days.
Our imaginative and prescient is to carry personalised gene remedy to the world. We goal to forestall, halt or reverse illness all through the physique with a single dose of gene remedy designed to drive sturdy expression of therapeutic protein, even in hard-to-reach tissues and organs together with mind, muscle and bone. Our ex vivo lentiviral gene remedy pipeline contains scientific applications in Fabry illness, Gaucher illness kind 1 and cystinosis, in addition to preclinical applications in Hunter syndrome, Gaucher illness kind 3 and Pompe illness. AVROBIO is powered by our trade main plato® gene remedy platform, our basis designed to ship gene remedy worldwide. We’re headquartered in Cambridge, Mass., with an workplace in Toronto, Ontario. For added data, go to avrobio.com, and comply with us on Twitter and LinkedIn.
This press launch comprises forward-looking statements, together with statements made pursuant to the protected harbor provisions of the Personal Securities Litigation Reform Act of 1995. These statements could also be recognized by phrases and phrases comparable to “goals,” “anticipates,” “believes,” “might,” “designed to,” “estimates,” “expects,” “forecasts,” “aim,” “intends,” “might,” “plans,” “potential,” “potential,” “seeks,” “will,” and variations of those phrases and phrases or comparable expressions which are supposed to determine forward-looking statements. These forward-looking statements embody, with out limitation, statements relating to our enterprise technique for and the potential therapeutic advantages of our potential product candidates, outcomes of preclinical research, the design, graduation, enrollment and timing of ongoing or deliberate scientific trials, scientific trial outcomes, product approvals and regulatory pathways, the timing of affected person recruitment and enrollment actions, and product approvals, anticipated advantages of our gene remedy platform together with potential impression on our commercialization actions, timing and probability of success, and the anticipated advantages and outcomes of our implementation of the plato® platform in our scientific trials and gene remedy applications, together with using a customized and ultra-precision busulfan conditioning routine. Any such statements on this press launch that aren’t statements of historic truth could also be deemed to be forward-looking statements. Leads to preclinical or early-stage scientific trials will not be indicative of outcomes from later stage or bigger scale scientific trials and don’t guarantee regulatory approval. You shouldn’t place undue reliance on these statements, or the scientific knowledge offered.
Any forward-looking statements on this press launch are primarily based on AVROBIO’s present expectations, estimates and projections about our trade in addition to administration’s present beliefs and expectations of future occasions solely as of in the present day and are topic to a lot of dangers and uncertainties that might trigger precise outcomes to vary materially and adversely from these set forth in or implied by such forward-looking statements. These dangers and uncertainties embody, however are usually not restricted to, the danger that anybody or extra of AVROBIO’s product candidates won’t be efficiently developed or commercialized, the danger of cessation or delay of any ongoing or deliberate scientific trials of AVROBIO or our collaborators, the danger that AVROBIO might not efficiently recruit or enroll a ample variety of sufferers for our scientific trials, the danger that AVROBIO might not understand the supposed advantages of our gene remedy platform, together with the options of our plato® platform, the danger that our product candidates or procedures in reference to the administration thereof won’t have the security or efficacy profile that we anticipate, the danger that prior outcomes, comparable to alerts of security, exercise or sturdiness of impact, noticed from preclinical or scientific trials, won’t be replicated or won’t proceed in ongoing or future research or trials involving AVROBIO’s product candidates, the danger that we’ll be unable to acquire and keep regulatory approval for our product candidates, the danger that the scale and development potential of the marketplace for our product candidates won’t materialize as anticipated, dangers related to our dependence on third-party suppliers and producers, dangers relating to the accuracy of our estimates of bills and future income, dangers referring to our capital necessities and wishes for added financing, dangers referring to scientific trial and enterprise interruptions ensuing from the COVID-19 outbreak or comparable public well being crises, together with that such interruptions might materially delay our enrollment and growth timelines and/or improve our growth prices or that knowledge assortment efforts could also be impaired or in any other case impacted by such crises, and dangers referring to our skill to acquire and keep mental property safety for our product candidates. For a dialogue of those and different dangers and uncertainties, and different essential elements, any of which might trigger AVROBIO’s precise outcomes to vary materially and adversely from these contained within the forward-looking statements, see the part entitled “Danger Components” in AVROBIO’s most up-to-date Quarterly Report on Type 10-Q, in addition to discussions of potential dangers, uncertainties and different essential elements in AVROBIO’s subsequent filings with the Securities and Alternate Fee. AVROBIO explicitly disclaims any obligation to replace any forward-looking statements besides to the extent required by legislation.
i Previously often called the FAB-201 trial
ii Collaborator-sponsored Section 1/2 scientific trial of AVR-RD-04 is funded partly by grants to UCSD from the California Institute for Regenerative Medicine (CIRM), Cystinosis Research Foundation (CRF) and Nationwide Institutes of Well being (NIH).