AIPL1

Results from the first four children to be treated have been detailed in a research paper. Credit: Tom Merton via Getty Images. MeiraGTx is advancing its investigational gene therapy toward expedited approval in the UK after 11 children who were born blind from birth gained significant vision improvements following treatment. The AAV-AIPL1 therapy is designed to address severe sight impairment caused by mutations in the AIPL1 gene. This condition is a form of retinal dystrophy that leads to severe visual impairment from birth, with affected individuals typically only able to distinguish between light and dark. The gene therapy involves injecting functional copies of the AIPL1 gene into the retina using an adeno-associated viral (AAV) vector, aiming to restore retinal cell function and prevent degeneration. Results from four of the 11 children were published in The Lancet on 21 February. The first four children treated were aged one to three years with severe retinal dystrophy linked to mutations in the AIPL1 gene. Each child received the therapy in one eye through subretinal injection. Outcome measures included visual acuity assessments, functional vision evaluations, visual evoked potentials, and retinal structure imaging. Before treatment, the children’s visual acuity was limited to light perception. At an average follow-up of three and a half years post-treatment, the treated eyes showed significant improvement, with visual acuity improving. In contrast, the untreated eyes’ visual acuity deteriorated to unmeasurable levels. Additionally, objective tests confirmed enhanced visual function and electrophysiological assessments indicated increased visual cortex activity specific to the treated eyes. Imaging revealed better preservation of retinal structure in treated eyes compared to untreated ones. MeiraGTx’s CEO Alexandria Forbes said: “These improvements extended outside the meaningful effects on vision and result in life-changing benefits in all areas of development including communication, behaviour, schooling, mood, psychological benefits and social integration.” Following these positive outcomes, a second cohort of seven children received treatment in both eyes. All 11 children treated with AAV-AIPL1 have so far exhibited meaningful visual improvements. One child experienced cystoid macular oedema in the treated eye, which partially improved over time and did not hinder the overall visual gains. No other significant safety concerns have been reported. In light of these findings, MeiraGTx has engaged in discussions with the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) and plans to submit AAV-AIPL1 for expedited approval. The company is also in talks with the US Food and Drug Administration (FDA) to explore accelerated approval pathways in the US. If approved, AAV-AIPL1 would be eligible for a priority review voucher (PRV). While gene therapies hold promise for rare diseases, commercialisation remains a challenge. High development costs, complex manufacturing processes, and limited patient populations often deter investment. Earlier this month, Italian charity Telethon Foundation submitted a marketing authorisation application (MAA) to the European Medicines Agency (EMA) for a gene therapy targeting Wiskott-Aldrich syndrome after the withdrawal of its commercial partner. This marks the second time the foundation has stepped in to support an abandoned gene therapy, following its efforts with simoladagene autotemcel for ADA-SCID. The foundation claims to be the first charity worldwide to take responsibility for drug production and distribution, highlighting the financial and logistical hurdles in bringing gene therapies to market. The incidence of AIPL1-associated severe retinal dystrophy is estimated to be around one in every million live births. During a call with investors, Forbes stated that the company is exploring all options to ensure global access to AAV-AIPL1, noting “strategic interest” in the therapy. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Optimise your cell therapy process: a guide to cell thawing Typically carried out at the point of care, errors in cell therapy thawing could compromise treatment efficacy, leading to significant patient impact as well as high costs and a compromised reputation for the product’s developer. 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These are “strong clinical data with clear evidence of efficacy in a huge unmet need pediatric population,” analysts wrote.\n Eleven children who were legally blind at birth all gained visual acuity after receiving MeiraGTx\'s investigational gene therapy, data that are prompting the biotech to seek accelerated approval in AIPL1-associated severe retinal dystrophy.Results from four of the 11 children were published in The Lancet Feb. 21.Visual acuity—measured with a child-friendly, game-like touchscreen test—in treated eyes improved after four or more weeks, while the acuity in untreated eyes became unmeasurable, according to the published results.The effects of treatment “extended outside the meaningful effects on vision and result in life-changing benefits in all areas of development including communication, behavior, schooling, mood, psychological benefits and social integration,” MeiraGTx\'s CEO Alexandria Forbes, Ph.D., said in the biotech\'s accompanying release. One child developed cystoid macular edema, a build-up of fluid, in their treated eye due to the therapy, researchers wrote in the article, which partially improved over time and didn’t prevent the child’s vision from improving. There were no other safety concerns, the scientists said.Evercore ISI analysts described the findings as “strong clinical data with clear evidence of efficacy in a huge unmet need pediatric population.”  “As should be expected from a subretinal approach, safety was clean,” the analysts added in a Feb. 21 note.After positive conversations with the U.K.’s medicines watchdog, the firm now plans to submit the gene therapy, called rAAV8.hRKp.AIPL1, for expedited approval in that country, according to the release.MeiraGTx, which is headquartered in New York and has R&D and manufacturing in England, has also been in discussions with the FDA on how to pursue accelerated approval in the U.S., the company added.The therapy uses an adeno-associated virus to deliver functional copies of the AIPL1 gene and is injected once directly into the eye.The study began with four children between the ages of one and three who were born with severe retinal dystrophy associated with mutated copies of the AIPL1 gene. These children were each treated in one eye. After the researchers saw the treatment was safe and seemed to be working, they gave the gene therapy in both eyes of a further seven children.

IPO letter in the billboard screen jxfzsy/Getty Images/iStockphoto MeiraGTx has filed with the U.S. Securities and Exchange Commission (SEC) its intentions to launch an initial public offering (IPO). New York City-based MeiraGTx has filed with the U.S. Securities and Exchange Commission (SEC) its intentions to launch an initial public offering (IPO) to raise $86 million. The company expects to use the money raised to advance several of its gene therapy products into and through clinical trials. The company expects ordinary shares will trade on the Nasdaq Global Market under the “MGTX” ticker symbol. Underwriters will be Bofa Merrill Lynch, Barclays, Evercore ISI and Chardan. According to the filing, the company currently has nine product candidates in preclinical to Phase I/II clinical trials for a variety of disorders, including achromatopsia (CNGB3 and CNGA3), X-linked RP (RPGR), RPE65-Deficiency (RPE65) and others. Its first area of clinical focus is eye diseases, with three ongoing clinical programs and a fourth expected to launch a Phase I/II trial in 2019. Both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted orphan drug designation to each product candidate in its ongoing clinical programs, including those to treat CNGB3, RPGR and RPG65, as well as for their product candidate to treat AIPL1. The FDA also granted rare pediatric disease designation for its programs to treat mutations in RPE65 and CNGB3 and Fast Track designation for its XLRP program caused by mutations in RPGR. The EMA gave it PRIME designations for its clinical program to treat mutations in CNGB3. MeiraGTx spun out of Kadmon Holdings in 2015. It also partnered with UCL Institute of Ophthalmology, a gene therapy spinout of Athena Vision . It is led by Alexandria Forbes, formerly of Kadmon. On April 23, MeiraGTx announced the FDA had granted Fast Track designation for AAV-RPGR to treat X-linked retinitis pigmentosa (XLRP) caused by defects in the retinitis pigmentosa GTPase regulator (RPGR) gene. “XLRP is a devastating condition that causes rapid progression to blindness and currently has no approved treatment options,” Forbes, president and chief executive officer of MeiraGTx, said in a statement. “This Fast Track designation is an important milestone for both patients living with XLRP and MeiraGTx, allowing our team to communicate closely and often with the FDA as we work to bring a much-needed therapy to patients. Marking the third regulatory milestone our ocular program has received this year, we look forward to continuing this momentum in our commitment to develop innovative gene therapy treatments for patients.” According to the S-1 filing with the SEC, the company’s second area of focus is xerostomia, a chronic and debilitating disorder of the salivary glands. It can be caused by several different attacks on the salivary glands, including radiation therapy for head and neck cancer and some autoimmune diseases. The company stated, “A Phase I clinical trial of our gene therapy product candidate, aAV-AQP1, is ongoing in patients who have survived cancer free for five or more years following treatment for head and neck cancer and are suffering from grade 2 or 3 radiation induced late xerostomia, or RIX….We also intend to initiate a Phase I/II clinical trial of AAV-AQP1 for the treatment of patients with chronic xerostomia caused by Sjogren’s syndrome, an autoimmune disease affecting more than two million people in the United States.”