Significant Catalysts And Company PR Error Present Significant Opportunity In AcelRx Pharmaceuticals

Submitted by Scott Matusow as part of our contributors program.

AcelRx Pharmaceuticals (ACRX) is a specialty pharmaceutical company focused on the development and commercialization of innovative therapies for the treatment of acute and breakthrough pain. Its lead product, ARX-01, is designed to address intravenous (IV) PCA problems which can cause harm to patients following surgery such as the side effects of the invasive IV route for morphine delivery and inherent potential programming and delivery errors associated with the complexity of infusion pumps. ARX-01 uses the generic pain medication sufentanil, which is a common anesthetic agent. The difference is in the method of delivery through AcelRx’s patented NanoTab technology. Patients receive their dosage of sufentanil sublingually (under the tongue) through this system, instead of the traditional IV drip. AcelRx emphasizes that sublingual delivery of sufentanil through its Nanotab system allows for more prolonged plasma levels relative to IV, a lower maximum concentration, as well as a more consistent concentration during dosing.

To minimize the possibility of abuse or overdose, the device is programmed to dispense only the amount prescribed via a pre-programmed schedule.

The post-operative pain market in the United States, Europe and Japan has been growing steadily over the last few years and is expected to reach $6.5 billion by 2018. Acelrx’s Nanotab tech could potentially grab a significant piece of this market, which makes its current market cap of $104.62M absurdly low when we factor in that the company already has 2 positive Phase III data releases, with ARX-01’s main data release due by June of this year.

Yet despite its multi-billion dollar size, the post-operative pain market remains under served. Annually, approximately 16 million procedures requiring post-operative pain control using intravenous patient-controlled analgesia (IV PCA) are conducted in the United States and 5 main European countries (UK, France, Germany, Spain and Italy), typically utilizing morphine or hydromorphone.

Studies report that up to 75% of patients experience inadequate pain relief after surgery. Inadequate pain relief can lead to decreased mobility, which increases the risks of other medical complications, including deep vein thrombosis and partial lung collapse, and can result in extended hospital stays — besides the fact that patients have to deal with the mental trauma of this pain, which can lead to an entirely different set of costly issues.

The many deficiencies associated with the current use of IV PCA that ARX-01 addresses are:

• Side effects associated with the most commonly used opioid, morphine, and its active metabolites
• Infection risk, analgesic gaps and decreased mobility associated with the invasive nature of IV delivery, and
• Medication errors, which in some instances may be fatal, due to the complexity of IV PCA pumps. Many IV PCA medication errors are the result of human factors such as programming errors.

According Acelrx’s Website,

“the estimated annual error rates are 407 errors per 10,000 people treated with IV PCA in the United States. The most common and serious types of errors involve human factors, such as mis-programming the PCA pump or administering the wrong dose. In 2002 and 2003, approximately 5% of operator errors reported to the FDA resulted in patient deaths. Approximately 56,000 adverse events were reported to the FDA between 2005 and 2009, prompting 70 Class II infusion pump recalls of devices that could cause temporary or reversible adverse effects and 14 Class I infusion pump recalls of devices that could cause serious injury or death. These issues with infusion pumps have resulted in the issuance of new draft guidance by the FDA, significantly increasing the data required to be submitted by manufacturers to address safety problems.”

As mentioned, ARX-01 has the potential to address many of the key disadvantages of IV PCA which also include:

• Reducing the incidence of drug-related side effects,
• Eliminating the risk of IV PCA-related infections, reducing analgesic gaps and enhancing mobility, and
• Eliminating the risk of pump programming errors.

ARX-01 is designed to provide a favorable safety, efficacy and tolerability profile, enabling the treatment to potentially become the new standard of care for patient-controlled analgesia. Use of ARX-01 should result in increased patient satisfaction and reduced overall healthcare costs.

According to PropThink from their December 2012 article, the post operative pain market is a multi-billion dollar opportunity;

“The NanoTab PCA System is a handheld device designed to allow patients to self-administer ‘NanoTabs’, a dissolvable formulation of the synthetic opioid analgesic sufentanil. Sufentanil NanoTabs are delivered sublingually (under the tongue) and providers can electronically limit dosing. Similarly, traditional IV PCA morphine allows patients to control the administration of analgesics as necessary, but the intravenous administration and side effects of morphine make it an imperfect therapy. The NanoTab system proved non-inferior to standard IV PCA morphine in a Phase III study that reported top-line data in mid-November, and both nurses and patients reported greater satisfaction with AcelRx’s system. If the Sufentanil NanoTab PCA System receives approval from the FDA (New Drug Application expected mid-2013), the market for post-operative analgesics is immense and offers significant revenue potential, even if AcelRx achieves only marginal penetration. The post-operative analgesic market topped $5.9 billion in 2010 and is expected to grow at a CAGR of 3% through 2017. Including the rest of the company’s pipeline, AcelRx could potentially address a substantial portion of the total pain management market, which is expected to reach $35B by 2017.”

On March 4, AcelRx announced top-line data results demonstrating that the second of three Phase III studies, and the first of two pivotal placebo-controlled Phase III studies for its investigational sublingual Sufentanil NanoTab PCA (patient-controlled analgesia) System met its primary endpoint:

– Patients experienced significantly greater reduction in pain as measured by SPID-48 vs. placebo (p=0.001) –
– Adverse events in sufentanil-treated patients similar to placebo –

The primary endpoint evaluated pain intensity over the 48-hour study period compared to baseline, or Summed Pain Intensity Difference (SPID-48), in patients following major open abdominal surgery. Results demonstrated that patients receiving Sufentanil NanoTabs realized a significantly greater SPID-48 during the study period than placebo-treated patients (p=0.001). Secondary endpoint data also showed that 24 hours and 72 hours after first dose, SPID was significantly greater in the sufentanil-treated patients than in the placebo-treated patients (p<0.001 and p=0.004 respectively).

The March 4th data followed the first of the three Phase III trials for the NanoTab system, with the first data set released in November of 2012. That trial evaluated NanoTab PCA effectiveness treating acute pain immediately following major abdominal or orthopedic surgery. The trial was a randomized 1:1 design comparing Sufentanil NanoTab PCA to IV-administered PCA morphine. Data demonstrated that the Sufentanil NanoTab PCA System was non-inferior (p<0.001) to IV PCA morphine for the primary endpoint of PGA (patient global assessment, an accepted means of evaluating pain control effectiveness) over the 48-hour period immediately after surgery as demonstrated by the combined percentage of patients with PGA ratings of “good” or “excellent” (78.5% vs. 66.1% respectively).

According to CEO Richard King,

“the company also collected a large amount of secondary endpoint data in the study. In particular, conclusions from validated ease-of-care questionnaires, configured by both patients and nurses during and at the end of the study, pointed to superiority in favor of the NanoTab System over IV morphine for both satisfaction and ease-of-care for both nurses and patients. Nurses identified the NanoTab System as less bothersome to set up and monitor than IV PCA. In addition, patients reported having high confidence in the NanoTab System, that they could ambulate more easily than when they were tethered to an IV PCA pump, and that they achieved better pain control from the NanoTab System than with IV PCA with morphine. In light of the fact that hospitals are very focused on achieving high patient satisfaction, since Medicaid and Medicare reimbursement and patient throughput are linked to this measure, there is reason to believe that the performance of the NanoTab System in this study supports prospects for commercial adoption once AcelRx has received regulatory approval.”

One additional pivotal Phase III double-blind, placebo-controlled study of the Sufentanil NanoTab PCA System is underway. The study began in August 2012, and is designed to enroll approximately 400 patients in a 3:1 randomization following hip or knee replacement surgery at up to 35 sites. The primary endpoint, SPID-48, is identical to the primary endpoint for the abdominal surgery trial. The company expects top-line results for this trial to be available in the second quarter of 2013, which should make for a nice catalyst price appreciation trade.

An October 3rd, 2012 announcement by the company noted that the three Phase III trials’ data would be sufficient to meet EMA requirements for regulatory approval if the data were positive. Marketing approval for the European Free Trade Association countries is very significant, representing a potential market tap from over 500 million people who reside in the area.

The company also has three additional product candidates in clinical development: ARX-02 for the treatment of cancer breakthrough pain; ARX-03 for providing mild sedation, anxiety reduction and pain relief for patients undergoing painful procedures in a physician’s office; and ARX-04, a non-invasive, fast-onset sublingual product for the treatment of moderate-to-severe acute pain.

At the end of 2012, Acelrx had $60M in cash and investments, which is more than enough capital to fund the company through Q3, 2014.

With the positive result of the first phase III study, coupled with the positive responses of nurses and patients initiated a substantial increase in the company’s share price, reaching a high of $5.19 in late November. As is often the case with developmental stage pharmaceuticals, however, the excitement was quickly muted in early December when the company announced a stock offering of 12.5 million shares at a price of $3.31. After netting $44 million from the stock offering, investors became comfortable with Acelrx’s cash position, and the stock began a nice climb back up and rallied to an intraday high of $5.97 on February 13.

Partnership/Buyout potential:

AcelRx CEO Richard King has continuously stated that the company plan is to bring ARX-01 to market in the U.S by themselves, and to seek out a potential partner for the rest of the global market. Unlike many developmental stage biotechs, AcelRX seems poised to take that route if necessary. In this 8k released on Jan 25^th, the company announced a material definitive agreement for the manufacturing of Sufentanil NanoTabs for use with the company’s Sufentanil NanoTab PCA System, or ARX-01. Additionally, King discussed his rollout plan, scalability, and projected sales force numbers on the conference call. Rumors of potential suitors are linked to nearly every biotech that nears FDA approval, and AcelRx is no exception. Big Pharma will almost certainly come calling soon, and King has done an admirable job positioning the company for any partnership or buyout talks. With a healthy cash position, a realistic rollout plan, a marketable story of patients and nurses preferring ARX-01, and a manufacturing agreement already in place, King will be negotiating from a position of strength.

Regardless of any partnership or buyout thoughts, AcelRx is a company I am comfortable with for at least a short term trade and potentially long term because of its upcoming catalysts and position in a huge market.  In addition, they just did a cash raise which gives them approx. $60 million to work with.

Considering the company’s solid cash position, positive late stage data, along with the substantially large market potential of its pipeline and a market cap of around $100M, Acelrx is both a strong long based trade and speculative long term investment.

My shorter term catalyst trade target opinion is 6.25, with a one year price target of $12.