According to a new report from the Alliance for Regenerative Medicine, there are a whopping 932 regenerative medicine companies worldwide that are in the process of developing 440 gene therapies, 587 cell therapies and 125 tissue engineering/biomaterials products.


Two of those regenerative medicine products gained regulatory approvals in the second quarter: Zolgensma (onasemnogene neparvovec) to treat spinal muscular atrophy (SMA) and Zynteglo (betibeglogene darolentivec) for the treatment of transfusion-dependent beta-thalassemia. (See BioWorld, April 1, 2019, and May 28, 2019.)

Novartis AG gained FDA approval for Zolgensma a little over a year after acquiring Avexis Inc. for $8.7 billion. The drug uses an AAV9 vector to deliver a functional SMN1 gene, which is mutated in SMA patients. The Basel, Switzerland-based company is charging $2.1 million for the treatment.

Cambridge, Mass.-based Bluebird got a positive opinion from the EMA's Committee for Medicinal Products for Human Use for Zynteglo in late March followed by the European Commission signing off in June. Combining gene and cell therapy, Zynteglo involves taking stem cells from patients, transfecting them with a lentiviral vector to express a working copy of the beta-globin gene and putting the repaired cells back into the patient.

"Novartis and Bluebird Bio have each introduced outcomes-based pricing over up to a five-year timeframe for their respective products, exemplifying the movement toward alternative payment models. Legislation is currently pending that would enable such payment-over-time/outcomes models to be used in Medicaid," the report notes.

Clinical data

Regenerative medicine products were being tested in more than 1,000 clinical trials at the end of June.

In May, San Rafael, Calif.-based Biomarin Pharmaceutical Inc. released phase III data for valoctocogene roxaparvovec, its gene therapy expressing factor VIII (FVIII) to treat severe hemophilia A. In a study testing the high dose of the therapy, the mean annualized bleeding rate was reduced from 10 at baseline to less than 1.5 at week 26. With expression through gene therapy, patients were able to reduce their annualized FVIII usage by a median of 84%, or 94% when measured between weeks five and 26. (See BioWorld, May 29, 2019.)

After disappointing investors earlier this year with 48-week data from its Rescue clinical trial of GS-010, in patients with 11778-ND4 Leber hereditary optic neuropathy (LHON), Paris-based Gensight Biologics SA reported follow-up 96-week data from another GS-010 phase III study, dubbed Reverse. Best corrected visual acuity improved from +14.7 ETDRS letters equivalent at week 72 to +15.4 ETDRS letters at week 96, although the improvement wasn't statistically better than the +12.9 ETDRS letters equivalent for sham-treated eyes. (See BioWorld, Feb. 5, 2019.)

On the regulatory front, the NIH recently eliminated its duplicate oversight of gene therapy, so sponsors will no longer have to register gene therapy programs with the agency and can focus their attention on the FDA's requirements.


Boston-based Vertex Pharmaceuticals Inc. announced a two-for-one gene editing deal, expanding its partnership with Crispr Therapeutics AG to include Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1) and acquiring Exonics Therapeutics Inc. (See BioWorld, June 10, 2019.)

Vertex is paying Crispr, of Zug, Switzerland, $175 million up front with the deal having the potential to reach $1 billion, including development, regulatory and commercial milestones for the two programs. Crispr has the option, at the time of IND filing, to forego the milestones and royalties for the DM1 products and choose to co-develop and co-commercialize all DM1 products globally.

Exonics, of Boston, was acquired for $245 million up front with the potential for earn-out payments to bring the deal total to approximately $1 billion if development and regulatory milestones are reached. In animal models, Exonics has used its SingleCut CRISPR to genetically repair and restore expression of dystrophin, the mutated gene in children with DMD.

Editas Medicine Inc. and Bluerock Therapeutics LP also hooked up in a cross-licensing and collaboration agreement, with Editas contributing its CRISPR genome editing technology and Bluerock adding its induced pluripotent stem cell platform. The companies plan to produce off-the-shelf cell therapies, with Bluerock focusing on neurology, cardiology and immunology, while Editas attacks oncology, including solid tumors and blood cancers. (See BioWorld, April 4, 2019.)


During the second quarter, regenerative medicine companies raised $2.6 billion, including acquisitions and up-front payments for partnerships, bringing the first half total to $4.8 billion.

While the first half financing is down 40% compared to the year-ago period, the decline is mostly due to the crazy IPO market that raised $1.9 billion in 2018 and the $4.7 billion raised in follow-on offerings in 2019. The 2019 IPOs have already raised more capital than IPOs in all of 2017, although the 2019 follow-on offerings are trailing 2017's pace.

Precision Biosciences Inc. raised $145 million in its IPO that closed at the beginning of April. A couple of weeks later, the newly public company from Durham, N.C., treated the first patient in a phase I/IIa study of PBCAR-0191, an allogeneic anti-CD19 CAR T-cell therapy that's edited with its ARCUS genome editing platform. The study is enrolling patients with relapsed or refractory (r/r) non-Hodgkin lymphoma or r/r B-cell precursor acute lymphoblastic leukemia.

Poseida Therapeutics Inc. delayed an IPO in favor of a $142 million series C round in April, with more than half — $75 million — coming from Novartis. San Diego-based Poseida will use the capital to continue development of P-BCMA-101, a nonviral autologous CAR T therapy for multiple myeloma, as well as a CAR T targeting PSMA on prostate cancer cells and an allogeneic CAR T targeting BCMA that should begin clinical development next year. The nonviral constructs use the company's Piggybac technology. (See BioWorld, April 23, 2019, and BioWorld Insight, Aug. 12, 2018.)

Following its $165.6 million IPO in 2018, Homology Medicines Inc. was able to raise another $144 million in April through a secondary offering. The Bedford, Mass.-based company plans to use the capital to get its gene therapy candidate, HMI-102, for the treatment of phenylketonuria (PKU) in adults, through a phase I/II study that began in June. The cash will also be used to advance HMI-202, a gene therapy candidate for metachromatic leukodystrophy, and HMI-103, a gene editing candidate for the treatment of PKU in children, through IND-enabling studies and potentially into initial clinical trials.

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