Pharmaceutical companies have been fielding a slate of new drugs for multiple sclerosis in the past few years—most recently the new oral pill diethyl fumarate (Tecfidera) that analysts see as a potential multibillion-dollar revenue source for Weston, MA-based Biogen Idec (NASDAQ: BIIB).
For the most part, however, the new MS drugs treat the progressive disease in its early stage, called relapsing-remitting MS, in which patients have periodic attacks of brain inflammation but then recover some of their lost muscle strength and other abilities. Unfortunately, doctors have little to offer patients who move into a later stage, secondary progressive MS, which causes a gradual and lasting decline in physical functioning.
It’s that later phase of the disabling neurodegenerative disease that the small Texas biotechnology company Opexa Therapeutics (NASDAQ: OPXA) decided to tackle. Opexa’s cell-based immunotherapy imilecleucel-T (Tcelna), if successful in clinical trials, could become the first “personalized” treatment for multiple sclerosis, says CEO Neil Warma (pictured above). The company uses a blood sample from each patient to generate cells designed to activate the immune system against the individual traits of that person’s disease. The cells are then re-injected into the patient.
Opexa is hoping its cell therapy will provide a much safer alternative to the currently approved drug for secondary progressive MS (SPMS), a repurposed cancer drug called mitoxantrone (Novantrone.) Side effects are often a significant drawback of MS drugs, but doctors have to be particularly careful with mitoxantrone, which comes with an FDA “black box” warning because it can have toxic effects on the heart.
“It’s rarely used, or it’s used with caution,” Warma says. Doctors may try keeping patients with SPMS on drugs approved for the relapsing form of MS, but often there’s little clinical evidence of efficacy in SPMS and a risk of side effects, Warma says. “An awful lot of patients are not taking anything,” he says.
Opexa, based in The Woodlands, TX, north of Houston, was once among the competitors in the crowded field of drug companies developing treatments for relapsing-remitting MS (RRMS). The Texas company saw encouraging efficacy trends and a reassuring safety record in a mid-stage trial of imilecleucel-T in both RRMS and SPMS patients that ended in late 2008, Warma says. Opexa received the FDA’s approval for a Phase 3 trial in RRMS.
But Opexa took a pause to regroup and plan its best path forward, says Warma, who became CEO in 2008. The company modernized processes at its manufacturing plant to prepare for the scale-up needed for a large clinical trial and the possible commercial launch of imilecleucel-T. Opexa also rearranged its priorities after listening to pharmaceutical industry advisors who said the company should pursue approval first in secondary progressive MS, an area of significant unmet need.
Multiple sclerosis is an unpredictable disorder whose effects vary among individuals from mild flare-ups to paralyzing disabilities. About 2.1 million people worldwide suffer from the disease, including at least 400,000 in the United States, according to the National Multiple Sclerosis Society. The relapsing form of MS accounts for about 85 percent of cases. But many early stage MS patients develop secondary progressive MS after 10 to 20 years, Warma says. A successful treatment for SPMS could compete for a 40 percent share of a U.S. market in MS drugs now worth as much as $12 billion a year, he says.
Opexa has emerged from its rebuilding phase over the past year, growing to more than 30 employees and adding experts in clinical research, manufacturing, and regulatory issues. In September, the company began a Phase 2 clinical trial of imilecleucel-T in 180 participants with secondary progressive MS. The drug has a fast track designation from the FDA.
Opexa’s experimental therapy is aimed at immune system cells called T-cells that go awry, attacking the sheath of myelin that insulates and protects nerves. Each MS patient’s destructive T-cells recognize particular sections of myelin proteins. Those peptide sections that set off the T-cell attack can be different from one individual patient to the next. The peptide triggers can also change over time for each patient as the myelin sheath deteriorates and different protein sections are exposed.
In Opexa’s ongoing trial, T-cells from each participant’s blood are induced to multiply. Like the damaging T-cells that occur naturally in patients with MS, the T-cells in preparations of imilecleucel-T react to the specific myelin peptides characteristic in each individual. But the artificially grown T-cells are irradiated, so they can’t multiply once the imilecleucel-T treatment is re-introduced into the body.
As Warma explains it, the flood of newly injected T-cells arouses the immune system to recognize the patient’s naturally occurring myelin-attacking T-cells as a threat to be destroyed. The injected T-cells, already weakened by irradiation, die off quickly.
Opexa expects to complete enrollment of the mid-stage trial in early 2014 and announce topline data in early 2016. So far, the company is funding the trial itself. But under a deal announced in February, Merck Serono has an option to license imilecleucel-T at any point during the trial and could pick up the full development costs.
Merck Serono, based in Darmstadt, Germany, is the biopharmaceutical division of German drug giant Merck KGaA (which is independent from Whitehouse Station, NJ-based Merck & Co.). The German conglomerate markets Rebif, an interferon beta product used for the relapsing form of MS. Merck’s U.S. affiliate, EMD Serono, sells mitoxantrone under the brand name Novantrone.
Under the Merck Serono deal, Opexa gained a $5 million upfront payment. A fundraising round early this year brought its total of new capital up to $9.5 million. Opexa’s cash trove will support its operations into the fourth quarter of this year. But Warma says the company will need to raise more money to keep going after that.
A success in SPMS could build the case for a Phase 3 trial of imilecleucel-T in the earlier, relapsing form of MS, Warma says. Despite the succession of new drugs approved for that early stage, current treatment options for RRMS leave room for improvement, he says. Side effects can be severe, or efficacy can be limited.
No drug offers a cure for any form of multiple sclerosis, but the new RRMS drugs have delivered substantial improvements. Biogen Idec’s diethyl fumarate (Tecfidera), approved by the FDA in March, was the latest of three drugs to offer MS patients the convenience of pills taken by mouth as an alternative to injectable drugs such as Rebif and glatiramer (Copaxone), a polypeptide marketed by Teva Neuroscience of Kansas City, MO.
Although big drug developers have raced to produce oral MS drugs, Warma says Opexa’s injected treatment could still be competitive. The company’s hope is that a therapy tailored for every patient, and made from their own cells, will deliver greater efficacy as well as greater safety than drugs currently available. If the data on imilecleucel-T in SPMS show such a favorable benefit/risk ratio, Opexa might be able to command a slight premium on the prevailing price of about $60,000 for a year’s treatment with current MS drugs, Warma says.
It’s too soon to say how many years an MS patient would take imilecleucel-T if the treatment is approved, Warma says. In the ongoing clinical trial, participants will receive a new preparation each year for two years. Trial investigators will take note whether there’s a change in the myelin peptides targeted by the T-cells in each individual from year to year. The performance of imilecleucel-T will be evaluated by measures of brain atrophy and other signs of disease progression.
Warma says big competitors such as Biogen Idec and Novartis are starting to explore the potential of secondary progressive MS treatments, perhaps because they think the relapsing form of MS is already well covered by a range of drugs.
“Hopefully, Opexa is ahead of the curve,” Warma says.