FDA rejects BioMarin’s gene therapy and Gilead’s filgotinib over concerns

The FDA refused to approve BioMarin’s hemophilia A gene therapy valoctocogene roxaparvovec. The U.S. regulator that had earlier told there was no requirement of an AdComm for the drug, aka, valrox, has issued a complete response (CRL) letter, which could cause a significant delay for any future approval, and canceled what would have been the first-ever approval for gene therapy in the bleeding disorder.

The removal of an AdComm was seen as a positive. Three-year data on its candidate were reported last year, but it sparked concerns regarding the durability of the therapy after factor VIII levels seemed to fall off after 12 to 18 months, increasing the possibility of patients needing to be re-dosed to maintain protection against bleeds.

The FDA has also rejected Gilead’s filing for approval of filgotinib in rheumatoid arthritis. Gilead is not likely to be able to refile until the next year, pushing it further behind its competitors for the JAK inhibitor market.

In revealing the complete response letter, Gilead said the FDA had asked data from two ongoing clinical trials, MANTA and MANTA-Ray, which evaluated the effect of the 200-mg dose of JAK1 inhibitor filgotinib on sperm concentrations. The FDA has also raised concerns regarding the overall benefit or risk profile of the filgotinib 200 mg dose.

Immune-evading cells with PD-L1 control diabetes in mice

Generating insulin-producing pancreatic beta cells from stem cells to substitute those damaged by the immune system is a promising approach for diabetes treatment. But it has proven challenging to make the cells responsive to glucose changes and stop an immune attack after the cells are transplanted.

Now, the scientists at the Salk Institute have found a potential solution to those problems. They created functional, 3D cell clusters called human islet-like organoids (HILOs) that restored glucose control in mouse models of diabetes without prompting immune rejection.

The team successfully protected HILOs from the immune system without genetic manipulation. If the method succeeds as a therapy, the patients who received islet transplants could avoid the need for chronic immunosuppression to increase the risk of dangerous infections.

J&J inks USD 6.5 Billion Momenta buyout to bag autoimmune drug

Johnson & Johnson has struck an agreement to acquire Momenta Pharmaceuticals for USD 6.5 billion. The takeover will proffer J&J control of an anti-FcRn antibody, which completed a phase 2 trial in myasthenia gravis earlier this year.

J&J has agreed to pay USD 52.50 a share in cash to get its hands on the anti-FcRn antibody, nipocalimab.

J&J’s willingness to pay that much shows its belief that Momenta can provide various blockbuster launches. Nipocalimab is in clinical development in myasthenia gravis, warm autoimmune hemolytic anemia (wAIHA), and hemolytic disease of the fetus and newborn indications.

Momenta has another asset, hyper-sialylated human immunoglobulin G m234, in the pipeline in immune thrombocytopenia purpura (ITP), but nipocalimab is a significant event. J&J is still to decide on plans for the other drugs.

Alzheon bags USD 47 Million NIH grant to bankroll Alzheimer’s trial

Alzheon is moving forward with a phase 3 study of its lead Alzheimer’s program, thanks to a USD 47 million grant from the NIH’s National Institute on Aging (NIA).

Over five years, the grant will support a study of ALZ-801. This pill inhibits amyloid oligomers’ formation or soluble amyloid molecules in the brain, which is thought to lead to Alzheimer’s disease.

Amyloid oligomers are clusters of individual amyloid proteins and represent a target that drugs can hit before full-blown amyloid plaques form. Many companies have tried to target amyloid plaques effectively, highlighting the need for new approaches in drug development of Alzheimer’s.
ALZ-801 is a prodrug of Tramiprosate, meaning the pill is metabolized inside the body to produce the drug. Tamiprosate has been tested in more than 2,000 patients with mild to moderate Alzheimer’s but did not move the needle in a general population. That is why Alzheon is taking a precision medicine approach with ALZ-801.