Pharm Exec’s 16th Annual Pipeline Report examines six key areas of biopharma R&D—a mix of emerging and maturing—where, for some, promising research efforts are now beginning to pay dividends, as novel advances in science usher in new treatment approaches and curative therapies.
Despite entering—or even strengthening already established footing—in today’s “new era of biopharmaceutical innovation,” developing novel drugs that will bring value and benefit to patients continues to be a difficult challenge. The common and very real prospect of failure will never go away. But, as Pharm Exec’s 16th Annual Pipeline Report illustrates, the arduous research efforts by life sciences companies are paying dividends, and leading to transformative and, in some cases, curative therapies.
For instance, cell and gene therapy (CGT), including CAR-T and the work with RNA interference (RNAi), is beginning to make an impact. The thousands of research papers and patents in areas ranging from CGT, to CRISPR technology, to CAR-T drugs for cancer are a testament that science will continue to breed new successes in product development, and will generate better outcomes for patients and value for the healthcare ecosystem as a whole.
More than 3,300 Phase II through IV CGT trials are underway, according to data provided by Signals Analytics, indicating how active R&D efforts are on this front. Oncology, hemophilia, Huntington’s disease, and sickle cell disease, as well as amyotrophic lateral sclerosis (ALS) are among those conditions targeted in clinical trials.
Research efforts include work with pluripotent stem cells (iPS), adeno-associated virus (AAV) gene therapies, and immune tolerance technology, among others. Novartis, Bayer, the National Institutes of Health, and several universities, among other entities, are involved. (Note that CRISPR technology and CAR-T therapies are the focus of their own sections later in this report.)
In early September, the UK’s National Institute for Health and Care Excellence (NICE) recommended a new gene therapy-based treatment for rare inherited eye disorder for use by the National Health Service. Luxturna (voretigene neparvovec), marketed by Novartis in Europe, is targeted to those who have lost their vision from inherited retinal dystrophy from confirmed RPE65 gene mutations and who have enough viable retinal cells.
The RPE65 gene provides instructions for making a protein essential for normal vision. Current treatment involves only supportive care, such as the use of low-vision aids. Clinical trials showed that, in the short term, Luxturna, which is injected directly into the retina, improves vision and prevents worsening of inherited retinal dystrophy.
On another front, Athersys is applying its patented MultiStem stem cell therapy for treating neurological, inflammatory, immune, and cardiovascular diseases, among other indications. For ischemic stroke, the company launched its Masters-2 Phase III pivotal study under special protocol assessment by FDA, and in partnership with Healios, a Phase II/III clinical trial recently commenced in Japan under a new accelerated regulatory framework. MultiStem has priority review designation from Japan’s Pharmaceuticals and Medical Devices Agency.
For graft-versus-host disease and hematopoietic stem cell transplantation, a Phase III pivotal study under special protocol assessment has been approved by FDA. The program was awarded orphan-drug status by FDA and the European Medicines Agency (EMA), and is being fast-tracked by FDA. (For more, see and listen to this Pharm Exec interview and podcast with Athersys CEO Gil Van Bokkelen. In August, Arrowhead Pharmaceuticals and Janssen Pharmaceuticals began dosing in a Phase IIb study of different combination regimens, including JNJ-3989 (formerly ARO-HBV), or JNJ-6379, and a nucleos(t)ide analog for treating chronic hepatitis B virus infection.
JNJ-3989 is a liver-targeted investigational antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection by RNAi. JNJ-6379 is an orally administered capsid assembly modulator of the class that forms normal capsid structures.
There also is interest in using cell and gene therapies to treat cystic fibrosis (CF) patients who experience persistent lung infections. There may be curative therapies found in using gene editing or therapy tools in stem cells. If a stem cell receives one of these therapies, every cell that is produced by the stem cell would also have the correct gene. For example, if an airway stem cell had a correct copy of the CF transmembrane conductance regulator (CFTR) gene, the new lung cells produced by that stem cell would also have a correct copy of the CFTR gene.
Scientists have shown that it is possible to make iPS cells using cells from people with CF, apply gene editing to correct CFTR mutations in those cells, and reimplant the correct cells into the lungs of CF patients.
Selecta Biosciences wants to combine its immune tolerance technology (ImmTOR) platform with several biologic therapies for rare and serious diseases that require new treatment options due to high immunogenicity. SEL-212, its lead product candidate, is being developed to treat chronic refractory gout patients and resolve their debilitating symptoms, including flares and gouty arthritis.
Abeona Therapeutics’ clinical programs include EB-101, an autologous, gene-corrected cell therapy for recessive dystrophic epidermolysis bullosa, as well as ABO-102 and ABO-101, novel AAV9-based gene therapies for Sanfilippo syndrome types A and B (MPS IIIA and MPS IIIB), respectively.
In August, Orchard Therapeutics announced it will balance its existing contract manufacturing organization (CMO) network with an internal facility to create the infrastructure needed to commercialize its gene therapies.
Orchard’s pipeline of ex vivo autologous gene therapies include five clinical stage programs and the former GlaxoSmithKline hematopoietic stem cell (HSC) gene therapy Strimvelis, which was approved by the EMA in 2016 for treating adenosine deaminase deficiency, an autosomal recessive metabolic disorder that causes immunodeficiency. It is still awaiting FDA approval.
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