- The stock price of Avrobio Inc (NASDAQ: AVRO) fell by 6.25% today. This is why it happened.
The stock price of Avrobio Inc (NASDAQ: AVRO) fell by 6.25% today. Investors are responding negatively to the company’s interim data from a collaborator-sponsored, ongoing Phase 1/2 clinical trial of AVR-RD-04, an investigational gene therapy for cystinosis, at the 18th Annual WORLDSymposium in San Diego.
The first 3 patients infused with AVR-RD-04 remain off oral cysteamine, with follow-up durations ranging between 12- and 26-months post-gene therapy infusion. And sustained engraftment has been observed in each of these patients, as demonstrated by stable vector copy number (VCN) levels. A fourth patient was infused in November 2021. No adverse events related to the drug product have been reported in the four patients infused to date.
Data support engraftment and potential durability with a reduction in symptoms
The collaborator-sponsored Phase 1/2 clinical trial is evaluating the safety and efficacy of AVR-RD-04 in adult patients who previously had been treated with cysteamine. And AVR-RD-04 consists of the patient’s own hematopoietic stem cells, genetically modified to express functional cystinosin, the protein that is deficient in people living with cystinosis.
The interim VCN data indicate that the first three patients dosed have potentially reached a plateau 12- to 26-months post-gene therapy infusion at levels between 1 and 2.6 VCN per diploid genome (dg). And VCN/dg is the average number of copies of the transgene integrated into the cell genome and is used to help assess the long-term engraftment and thus durability of gene therapy.
Skin and intestinal mucosa biopsies for the first 3 patients infused indicate a decline in the number of cystine crystals, with one-year reductions in average intracytoplasmic crystals per cell in skin ranging from 35% in patient 1, 64% in patient 2, and 81% in patient 3. In rectal biopsies, a 53% reduction was observed in patient 1 after 18 months, and 28% and 86% reductions were observed in patients 2 and 3, respectively, after 12 months. A hallmark of cystinosis is the accumulation of cystine in lysosomes, a type of cellular organelle, which leads to tissue and organ damage resulting in debilitating co-morbidities.
Why Did The Price Fall?
Investors appear to be responding to the company’s timeline, which was revealed in a company filing. The company is going to deploy a registrational-quality Phase 2 study in 2 stages (in pre-renal transplant patients in the first stage and in post-renal transplant patients in the second stage), which will not be initiated until 2023.
But there is still potential to accelerate the development of the pre-renal transplant part of the trial — which could bring ARV-RD-04 to the market sooner.
The “buy the rumor, sell the news” effect also seems to be in play.
“The significant unmet need of people living with cystinosis remains the compelling impetus for the development of new treatments. Under existing drug regimens that are both burdensome and frequently carry substantial side effects, patients still face relentless disease progression and the prospect of debilitating symptoms, kidney transplantation with life-long immunosuppression therapy and significantly shortened lives. These interim data increase our confidence in the safety and efficacy of our gene therapy approach using the patient’s own hematopoietic stem cells and lay the groundwork for the AVROBIO-sponsored clinical trial for cystinosis planned to begin in 2023.”
— AVROBIO President and CEO, Geoff MacKay
“Although this is interim data, we believe that the favorable safety profile observed to date, combined with sustained engraftment and consistent data across multiple other clinical measures, establish proof-of-concept in adult patients and support our view that gene therapy using a patient’s own hematopoietic stem cells given as a single infusion has the potential to be effective against this devastating disease.”
— AVROBIO Chief Medical Officer, Essra Ridha, M.D.
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