Upcoming events: Phase III confirmation for Amgen's T-Vec and Otsuka's brexpiprazole

Welcome to your weekly digest of approaching regulatory and clinical readouts. Mature overall survival (OS) data is expected in the first half of the year from Amgen’s oncolytic virus talimogene laherparepvec in melanoma. While positive trends in response rates and OS have been reported, the rapid progress being made with the anti-PD-1s means a very strong readout is needed for the product to remain relevant.

The European Congress of Psychiatry is taking place March 1-4 in Munich, Germany. First phase III results on brexpiprazole, Otsuka’s potential Abilify successor, are expected on March 2. Headline data from the trial in major depressive disorder looked good, and with further results reading out in the coming months in schizophrenia, expectations are rising for brexipripazole to help alleviate Otsuka’s patent woes.

Amgen: talimogene laherparepvec (T-Vec)

Amgen recruited over 400 patients with unresected stage IIIB, IIIC or IV melanoma for the phase III study, which compared talimogene laherparepvec or T-Vec to GM-CSF, a white blood cell growth factor that can help to activate the immune system. The oncolytic virus was given intralesionally every two weeks, with GM-CSF administered subcutaneously.

Last year Amgen reported interim data showing statistically significant durable response rate (DRR), the primary endpoint, with 16% DRR in the T-Vec arm, versus 2% in the GM-CSF arm. The overall response rate was 26% with T-Vec and 6% with GM-CSF (Asco – Despite promise, future of oncolytic viruses remains clouded, June 3, 2013).

More importantly positive trends in overall survival (OS) were also seen although not statistically significant at this point. The median OS was 23.3 months in the T-Vec arm and over 19 months in the GM-CSF arm. The hazard ratio was 0.79 with a p value of 0.07. A more profound benefit was evident in patients with stage IIIB, IIIC, or IV M1a disease (HR=0.56) and in patients who received T-Vec as first-line treatment (HR=0.49).

Serious adverse events occurred in 26% of T-Vec patients and 13% of GM-CSF patients. The most common were disease progression in both arms, and cellulitis and pyrexia (fever) in the T-Vec arm.

In combo

The current biggest seller in melanoma is Bristol-Myers' intravenous Yervoy, but the new anti-PD-1 antibodies have shown robust data in this cancer type. As such, many believe the commercial outlook for T-Vec depends heavily on its use in combination with other agents.

Earlier this month Merck announced collaborations with its anti-PD-1, MK-3475 or lambrolizumab, that included testing it with T-Vec (Merck tries to climb back into PD-1 combo race, February 6, 2014). The phase Ib/II trial is expected to start later this year.

A phase Ib/II trial testing T-Vec in combination with Yervoy, compared to Yervoy alone, is currently looking to recruit 149 patients. The primary completion date is December 2015.

Current sales expectations for T-Vec are low with 2018 forecasts at $55m according to EvaluatePharma. T-Vec also suffers from its route of administration; it needs to be injected directly into tumour tissue, reducing its practicality. With oncolytic viruses still needing validation, Amgen has a tough battle on its hands to establish this agent as viable option.

22nd European Congress of Psychiatry, Munich, Germany

First phase III data from Otsuka and Lundbecks’ brexpiprazole will be presented at a poster session at the congress on March 2. The Pyxis trial studied brexpiprazole as an adjunctive therapy to antidepressants in patients with major depressive disorder (MDD). Three additional studies in depression and schizophrenia will conclude in the first half of this year and a US filing is expected in April or June.

Headline Pyxis data showed statistically significant improvements in the primary endpoint, mean Montgomery-Asberg Depression Rating Scale (MADRS) total score, in patients receiving treatment compared with placebo. All secondary endpoints showed a statistically significant advantage over placebo.

Commonly reported adverse events in the test group were weight gain, 8%, and akathisia (restlessness) at 7.4%. Analyst’s have pointed out that weight gain is at a slightly higher incidence than experienced with Abilify.

Sales in 2018 are forecast to reach $638m according to EvaluatePharma, which results in an NPV of $2bn for Otsuka, equivalent to 12% of the company's market value. Brexpiprazole is predicted to become the Japanese drug maker's second largest growth driver, behind its once-monthly injected version of Abilify, Abilify Maintena.

With the original Abilify pill losing US patent protection next year resulting in the loss of $3bn of sales, brexpiprazole needs to live up to high expectations.

Trial ID
T-Vec versus GM-CSF NCT00769704
Pyxis NCT01360645

All information is sourced to analyst notes and the EvaluatePharma Calendar of Events tool.

To contact the writer of this story email Joanne Fagg in London at joannef@epvantage.com or follow @JoEPVantage on Twitter

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