By Rex Graham
Scientists who have evaluated a variety of drug candidates to treat methamphetamine addiction (all of which failed in efficacy tests) are “gleeful” about significant positive clinical results of a novel type of drug being development by San Diego biotech company MediciNova, Inc. (MNOV).
Quitting methamphetamine is extremely difficult. Withdrawal triggers toxicity in the brain that lasts from months to more than a year, leaving addicts feeling “foggy,” slow and unable to continuously concentrate on many tasks. However, those taking MediciNova’s ibudilast in a phase 1b clinical trial performed significantly better than a placebo group in a battery of mental tests that require accuracy and attention.
The researchers conducting the trial at UCLA’s Center for Behavioral and Addiction Medicine have tested every promising drug-treatment candidate for methamphetamine addiction, and Steven Shoptaw, a professor at the center, said ibudilast has emerged as the only one with significant positive results. The news is meaningful because there is no U.S. Food and Drug Administration (FDA)-approved drug to treat methamphetamine addiction, and ibudilast is MediciNova’s lead drug candidate. Ibudilast also is in trials to treat multiple sclerosis (MS).
Methamphetamin’s cost to U.S: $23 billion
Methamphetamine-type stimulants have become the second-most abused drug type worldwide. Meth is easy to manufacture and when authorities take out kitchen-sized meth labs in homes and other buildings from Nebraska to Nigeria, residues of the drug left behind seep out and seriously sicken new occupants. Annually, about 1.2 million Americans use the inexpensive drug with street names like bikers’ coffee, poor man’s cocaine, crank and crystal, and one-third can’t quit.
A Rand Corporation study estimated the economic cost of methamphetamine use in the U.S. alone reached $23.4 billion in 2005. With an estimated 439,000 addicts in the U.S. unable to stop swallowing, snorting, injecting or smoking methamphetamine, the National Institute for Drug Abuse (NIDA), which is part of the National Institutes of Health (NIH), has made the development of a treatment for withdrawal a top research priority. The FDA gave fast-track status to ibudilast in February 2013.
Shoptaw said in an interview with San Diego Biotechnology Connection that ibudilast significantly improved the performance of mental tasks and attention of addicts who took ibudilast as part of the phase 1b double-blind, placebo-controlled trial conducted during a 27-day in-patient stay.
Shoptaw explains in a video why he is optimistic about ibudilast:
Treatment of meth addiction with PROMETA™ made headlines in 2006, prompting patients and their families to spend up to $15,000 to purchase the “miracle cure” from franchised for-profit treatment centers. However, PROMETA™ and other once-promising treatments for methamphetamine addiction have failed miserably in rigorous trials at academic centers.
“Buproprion, we’ve tried in several trials; it works in some people, but it doesn’t work in others,” Shoptaw said in a June 18, 2012, interview with San Diego Biotechnology Connection. “We tried Modafinil; that doesn’t work. We tried baclofen. We’ve tried gabapentin. We’ve tried amantadine. There has been a whole slew of drugs we’ve tried over the years and nothing has shown efficacy, so the idea that in an 11-patient [ibudilast] study we get a significant finding with attention and continuous performance tasks makes us gleeful, and it also makes us very sober because we have to do it again.”
Ibudilast was approved in Japan more than 20 years ago and has been prescribed to over one million patients for asthma and other medical conditions. It has a good safety profile in nearly 15,000 patients studied.
Ibudilast clinical trials
The phase 2 trial of ibudilast, using the most effective dose, 100 mg per day, will start in July 2013 and enroll 140 patients.
HIV-infected people who use methamphetamine face a heightened health risk because the drug further dampens their already-impaired immune systems, and tends to reduce their adherence to HIV-treatment regimens. In the phase 2 trial to being in July 2013, half of the 140 participants will be people who are HIV positive.
MediciNova’s lean business approach
MediciNova has maintained a lean corporate model, relying on collaborations with medical centers like UCLA, and federal grants to advance ibudilast.
MediciNova’s share price has risen as high as $4.63 and fell as low as $2.31 in the past nine months. The stock rose 25 percent after Shoptaw announced the phase 1b results on June 18, 2012, at the annual meeting of the College on Problems of Drug Dependence in San Diego.
The UCLA group’s rigorous evaluations of ibudilast’s health effects and influence on neurological performance have clearly demonstrated safety and efficacy. The group, which includes distinguished addiction specialist Keith Heinzerling, has a $3 million grant from NIDA to conduct the phase 2 trial.
Caution and passion
MediciNova has collaborated closely with Heinzerling, Shoptaw and their team at UCLA. “It’s a team of people that not only has the scientific, medical interest and caution and scrutiny, but still have the passion to affect, positively, human health,” said Kirk Johnson, MediciNova’s chief scientific officer.
Unlike other drug candidates to treat methamphetamine dependence and withdrawal, ibudilast is a non-opioid that doesn’t make addicts feel high. Instead, ibudilast helps addicts feel close to normal by reducing withdrawal symptoms. The drug is an inhibitor of phosphodiesterase 4 (PDE4) and PDE-10. (Viagra is an inhibitor of PDE5.)
Ibudilast inhibits a variety of inflammatory processes in the brain and decreases the activation of brain glial cells, which is thought to contribute to its therapeutic action. Ibudilast also is being developed by MediciNova to treat MS, which affects 250,000 to 350,000 people in the U.S. Ibudilast reduces brain-volume loss, or atrophy, commonly associated with progressive MS, in a dose-related fashion over at least 10 months.
Ibudilast for MS
In January 2012 MediciNova was awarded a method-of-use patent, which would expire no earlier than 2029 and covers a method of treating primary progressive multiple sclerosis (PPMS) or secondary progressive MS (SPMS) by administering ibudilast alone or with other drugs.
However, ibudilast’s first use, if clinical trials continue to show positive results, may be to treat meth addiction.
“We anticipate [FDA] drug approvals in 2016 to as late as the 2020 timeframe,” said MediciNova’s Johnson. “All of our clinical development recently and moving ahead is essentially funded by the NIH or divisions of NIH.”
The company has only a dozen full-time employees plus a consulting network. MediciNova had occupied a 5,089-square-foot office in La Jolla, Calif., for $12,672 a month. On Feb. 27 the company leased a 5,219-square-foot office nearby for an initial rate of $10,700 a month, increasing to $12,800 a month in March 2017. “Because we’ve got low internal expenses and grant support, our funding needs are not as high as some people would anticipate,” Johnson said.
MediciNova seeking business alliances
Upon completion of the phase 2 trials, MediciNova said it will seek strategic alliances “with leading pharmaceutical or biotech companies to support further clinical development, and plan to maintain certain commercialization rights in selected markets.”
MediciNova has eight products in its product pipeline, but it is primarily developing ibudilast and MN-221 (bedoradrine), a novel, highly selective ß2 -adrenergic receptor agonist being developed for the treatment of acute exacerbations of asthma and chronic obstructive pulmonary disease.
The U.S. Patent and Trademark Office recently notified MediciNova that the agency will approve the company’s application to patent the intravenous use of MN-221 (bedoradrine) for the treatment of acute exacerbations of asthma. MediciNova acquired the worldwide (excluding Japan) licensing rights to MN-221 from Kissei Pharmaceutical Co., Ltd., for $2.5 million.
Funding MediciNova’s strategic plan
MediciNova had $4 million in cash on hand to start 2013 and has raised another $1.5 million, but needs more to execute its strategic plan. The company has a common stock purchase agreement with Aspire Capital Fund LLC. MediciNova plans to cause Aspire to acquire up to 3.2 million new shares of stock not to exceed $20 million, and the company is pursuing other opportunities to raise capital. MediciNova has about 20 million shares outstanding as of June 2013.
MediciNova’s sophisticated yet spare drug-development approach, the expected upside from positive phase 2 results, and likelihood of significant business collaborations lead me to be cautiously optimistic about MediciNova.
I recommend MediciNova to investors as a calculated risk. It has cut its overhead and employee compensation, including stock-based compensation, and has a viable fundraising plan and options to collaborate with larger pharmaceutical companies. Issuing more stock involves dilution of its outstanding shares by up to 16 percent, but that is far less than the upside potential, which one analyst estimated is 100 percent.
Disclosure: Rex Graham owns MediciNova common stock.