Biogen’s tofersen fails to meet the primary goal in the Phase III ALS trial

Biogen has announced that its investigational antisense drug, tofersen (BIIB067), flunked to meet the primary goal of Phase III VALOR clinical trial in superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS) patients.

Although the drug did not reach the primary goal, the company says that trends favouring tofersen were observed across various secondary and exploratory measures of biologic activity, and clinical function.

Tofersen was licensed by Biogen from Ionis Pharmaceuticals under a collaborative development and licence agreement.

The randomised, placebo-controlled, double-blind Phase III trial evaluated the safety, efficacy, tolerability and pharmacodynamics of 100mg tofersen in subjects with SOD1-ALS, a rare type of ALS.

It enrolled a total of 108 subjects who received either tofersen or placebo.

An open-label extension study (OLE) is currently underway. Out of the 108 subjects who were part of the VALOR trial, 95 have been enrolled.

The change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score from baseline to week 28 was the trial’s primary efficacy goal.

Tofersen did not meet statistical significance on the primary endpoint in faster-progressing patients.

Phathom’s erosive esophagitis drug bests Prevacid in head-to-head phase III trial

Phathom Pharmaceuticals’ erosive esophagitis drug vonoprazan performed as well as over-the-counter Prevacid in a head-to-head phase 3 clinical trial, potentially planning a 2022 application for FDA approval.  

Vonoprazan is a potassium-competitive acid blocker, or P-CAB, under investigation to alleviate heartburn and cure all severities of erosive esophagitis. Patients with this condition have inflammation of the esophagus, which is often caused by backed-up stomach acids, infection, some medications and allergies.

In the phase III PHALCON-EE trial, vonoprazan was compared with Takeda’s Prevacid, a common over-the-counter medication for decreasing acid and treating the symptoms of stomach and intestinal ulcers. Phathom analysed its therapy in an initial healing and maintenance phase during the study, as per the company release. 

Vonoprazan reached the primary goal of the trial in the healing phase by demonstrating non-inferiority to Prevacid. Phathom’s therapy saw a healing rate of 93% compared to 85% for Prevacid. The drug also reached a secondary endpoint showing faster healing than Prevacid in patients with moderate-to-severe disease at Week 2.

Vertex reports success in one patient after islet cell therapy

Vertex is providing an initial peek at the first patient to receive a new type of diabetes cell therapy that could stop the requirement for a cell transplant.

A single patient with type 1 diabetes achieved a robust restoration of islet cell function after receiving VX-880. Restoration of these cells could enable patients to regulate insulin or even produce it independently, rather than use daily insulin treatment or look for an islet cell transplant.

RBC Capital Markets said the single-patient data shows proof of concept for Vertex’s therapy, which could be a “game-changing off-the-shelf approach.” The data where on one patient is not considered significant when testing traditional drugs; it is considered more significant for treatments such as cell and gene therapies.

The patient, who has been dependent on insulin treatment, received a single infusion of Vertex’s VX-880 at half the target dose as well as immunosuppressive therapy during the phase 1/2 clinical trial.

In the year before receiving VX-880, the patient had five life-threatening hypoglycemic episodes, which is when the blood sugar reduces to a dangerous level and was not making insulin.

After treatment, the patient was able to reduce the insulin dose and showed signs that the body was producing insulin on its own. Safety was similar to typical immunosuppressant therapy, and no severe side effects related to the treatment were reported. The patient did, however, experience one severe adverse event, which Vertex said was a rash unrelated to treatment.

VX-880 is a stem-cell-derived islet cell replacement therapy Vertex picked up in September 2019 in its USD 950 million Semma Therapeutics buyout. The therapy won a fast-track tag from the FDA in March.

Natera launches lung DNA test for capturing transplant rejections

Capturing the tiny pieces of DNA found circulating in the bloodstream has made headlines as the basis of liquid biopsy tests for cancer. Still, Natera focuses on using the same technology for a diagnostic zeroed in at observing the progress of organ transplants.

The company has now launched its genetic Prospera test for lung transplant recipients, a new addition to its latest formed patient observing portfolio, including kidney- and heart-focused versions. The blood test sifts for donor-derived, cell-free DNA from transplanted tissues and examines the genetic material for signs of rejection.

This can proffer a non-invasive surveillance alternative to bronchoscopic biopsy tests, as per Natera, by identifying organ injuries as well as difficult-to-spot infections. 

The Prospera test’s commercial rollout comes soon after clinical data for the diagnostic was touted earlier this month as a late-breaking presentation during the annual meeting of the American College of Chest Physicians.

A prospective validation study conducted by The Ohio State University’s lung transplant program compared 204 blood tests with lung tissue biopsy samples taken from 104 organ recipients. Thirty-five cases of acute organ rejection occurred, with the Prospera test displaying a negative predictive value of 97.33% to help eliminate the condition.

David Ross, Natera’s medical director for lung transplantation, said in a statement that the Prospera test has been clinically confirmed as a tool for evaluating both kidney and heart rejection in transplant patients, and they are excited to confirm it for lung transplant assessment as well.