Investors in Heron Therapeutics Inc. received the good news they were awaiting when the phase III MAGIC study of Sustol (granisetron injection, extended release) hit its primary endpoint as part of a three-drug regimen together with the intravenous (I.V.) neurokinin-1 (NK1) receptor antagonist fosaprepitant and the I.V. corticosteroid dexamethasone to prevent delayed-onset chemotherapy-induced nausea and vomiting (CINV) following administration of highly emetogenic chemotherapy (HEC) agents.

The findings for Sustol – the first 5-hydroxytryptamine type 3 (5-HT3) antagonist to show superiority to standard of care for delayed nausea and vomiting after HEC – worked their magic on Heron's shares (NASDAQ:HRTX), as well, which rocketed 71.8 percent to a 52-week high of $21.22 before closing at $19.76 for a gain of $7.41 on the day. More than 19 million shares – nearly 70 times the daily average – changed hands.

"This is a great day for patients," Heron CEO Barry Quart told BioWorld Today, suggesting the findings confirmed the significant need for improvement in treating and preventing delayed CINV after HEC. "This is why I come to work every day."

The Redwood City, Calif.-based company has had a long haul with Sustol, the subject of two previous FDA complete response letters (CRLs). Quart, who joined Heron in 2013, rebranded the company (previously A.P. Pharma Inc.) and moved quickly to resolve issues with the manufacturing supply chain, the primary focus of the CRLs.

The MAGIC study was not even required by the FDA. Heron proactively conducted the additional phase III to differentiate its product by demonstrating its thesis for Sustol in delayed-onset CINV after HEC.

The findings suggest the move paid off. MAGIC is the first phase III CINV prophylaxis study in a HEC population to use the current standard of care – in this case, Zofran (ondansetron, Glaxosmithkline plc) – as the comparator drug in the regimen. The study was conducted entirely in the U.S., mostly at community oncology centers rather than academic medical settings, Quart pointed out, enrolling more than 900 patients undergoing HEC treatment for various tumor types.

"We selected ondansetron as the comparator of choice because it's one of the most commonly used comparators in CINV trials and it's been reviewed by the FDA as an appropriate comparator to evaluate the effect of the drug in delayed nausea and vomiting in patients receiving HEC," Quart explained on a conference call with analysts.

The study met the primary endpoint – the proportion of patients who achieved a complete response, defined as no emesis and no rescue medications during the delayed-onset phase of CINV – with statistical significance of 64.7 percent in the Sustol group compared to 56.6 percent in the comparator group (p = 0.014).

The percentage of patients who achieved complete control, defined as complete response plus no more than mild nausea during the delayed-onset phase, also reached statistical significance in favor of Sustol (p = 0.022), according to Heron, with Quart calling the magnitude of outcome difference "compelling."

The percentage of patients who experienced no nausea or infrequent nausea during the delayed-onset phase was significantly higher in the Sustol arm compared with the comparator arm (p = 0.032), and the company said more patients in the Sustol arm were satisfied with their therapy based on a quality-of-life questionnaire (p = 0.040).

Sustol was well tolerated, with no clinically significant differences in the rate or severity of adverse events (AEs) between the two study arms. Company officials said injection site reactions observed were consistent with previous trials and generally mild, as were the majority of AEs observed in the study.

Sustol is formulated with Heron's Biochronomer drug delivery technology, designed to maintain therapeutic drug levels of granisetron for up to five days with a single subcutaneous injection. Although granisetron has a relatively short half-life, thus benefiting from the company's extended-release formulation, the drug has a long history of use and a demonstrated safety record, without the cardiotoxicity observed with many other 5-HT3 antagonists, Quart pointed out.

DATA SHOULD 'EASILY ALLOW FOR AN EARLY 1Q16 APPROVAL'

Heron has only received and analyzed "20 or 30 tables out of 100 or so" from the MAGIC study, but its focus is shifting quickly to resubmission of the new drug application for Sustol, which Quart aims to achieve by the end of June. With an anticipated six-month PDUFA date, based on the response to the CRL, "I want to see this drug approved this year," he said, though he quickly added, "either way, the launch is still planned for the first quarter of next year."

Heron, which in April reported full enrollment in the MAGIC study, plans to take Sustol to market on its own using a targeted sales force of fewer than 100 reps – a ploy that piggybacks on the exposure to Sustol gained by many community oncologists during MAGIC, Quart pointed out. (See BioWorld Today, April 3, 2015.)

The MAGIC findings received solid support from the analyst community.

"Importantly, the trial was 90 percent powered for a 10 percent relative difference in response rate and was able to show a 14.3 percent relative difference," Brean Capital LLC analyst Jonathan Aschoff wrote in a company update.

"Heron can now resubmit its Sustol NDA by mid-2015 and the new superiority data, together with manufacturing data from its current, different contract manufacturer, should be enough to easily allow for an early 1Q16 approval," he added. "In our view, the new management has clearly rectified all that has stymied Sustol in the past."

Jefferies Group LLC analyst Biren Amin agreed, calling the findings "the MAGIC touch" and raising the company's price target to $28 from $22.

"Data from the trial [are] expected to potentially lead to a broader, differentiating FDA approved label, since Aloxi [palonosetron, Eisai Inc.] is not currently indicated to treat delayed HEC," Amin wrote. "As a reminder, Aloxi showed a 7 percent improvement over ondansetron in its pivotal trial, and did not demonstrate superiority due to the smaller trial size. Positive data from the MAGIC trial likely leads to a broad CINV label and would differentiate from Aloxi's approved indications."

Leerink Partners LLC analyst Jason Gerberry predicted Sustol will become the new standard of care in CINV – a market that encompasses approximately 75 percent of the estimated 7 million annual chemotherapy patients in the U.S.

"Sustol is the only 5-HT3 for CINV treatment to have shown a statistically significant benefit in delayed CINV in HEC patients, which represent approximately 20-25 percent of the overall market," he wrote. "We expect 5-HT3s to remain a backbone of CINV treatment and Sustol to receive FDA approval with the differentiated HEC label which we believe will: (1) support faster adoption among specialists; (2) allow for premium pricing to the current market leader Aloxi; and (3) support payer coverage."

Gerbery projected peak sales of approximately $430 million assuming a conservative estimate of just 25 percent of market share for Sustol.

No Comments