Biogen will expand its ophthalmology portfolio with two potential first-in-class gene therapy candidates.

Biogen has a strategy to develop and expand a multi-franchise neuroscience pipeline across complementary modalities, according to CEO Michel Vounatsos. To accelerate the company’s entry into ophthalmology, Biogen announced that it will acquire London-based gene therapy company Nightstar Therapeutics for approximately $800 million.

Nightstar is a clinical-stage gene therapy company focused on adeno-associated virus (AAV) treatments for inherited retinal disorders that would otherwise lead to blindness. The biotech has potential first-in-class mid- to late-stage clinical assets, as well as preclinical programs with the potential to create long-term value, according to Vounstsos.

Nightstar’s lead candidate, NSR-REP1, is a gene therapy in phase III development for the treatment of choroideremia (CHM), a rare, degenerative, X-linked inherited retinal disorder that leads to blindness and has no approved treatments. Patients with CHM are mostly males with loss of function of the CHM gene, which encodes the Rab escort protein-1 (REP-1), a protein important in intracellular protein trafficking. When this protein is not functioning effectively, waste products are not properly eliminated from the retinal pigment epithelium and photoreceptors.

Administered by subretinal injection, the AAV vector in NSR-REP1 provides a functioning CHM gene and expression of the REP-1 protein. Treatment restores membrane trafficking and thus may slow, stop or potentially reverse the decline in vision. In a Phase I/II trial, patients treated with NSR-REP1 not only exhibited potentially meaningful slowing of decline in visual acuity compared with their historical levels of progression, but some also experienced improved visual acuity. Data from the ongoing phase III study is expected in the second half of 2020.

NSR-RPGR is Nightstar’s second lead candidate and is in a clinical trial for the treatment of X-linked retinitis pigmentosa (XLRP), a rare inherited retinal disease primarily affecting males with no approved treatments. In this disease, mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene result in a lack of active protein transport in photoreceptors, which leads to a loss of the photoreceptor cells. Retinal dysfunction is generally observed by adolescence and early adulthood, with legal blindness occurring when patients reach their 40s.

NSR-RPGR is also an AAV vector administered by subretinal injection. It provides a functioning RPGR gene that leads to expression of the RPGR protein and restoration of photoreceptor function, which may slow, stop or potentially reverse the decline in vision. In a phase I/II clinical trial, NSR-RPGR was shown to lead to an increase in central retinal sensitivity. The phase II/III dose expansion portion of this trial is currently underway.

Nightstar’s preclinical pipeline includes NSR-ABCA4 for Stargardt disease and potential programs targeting Best vitelliform macular dystrophy (Best disease) and other genetic forms of retinitis pigmentosa.