Eleven years after spinning out of Bayer, Aicuris has finally got across the finish line with its lead project, Prevymis. Or rather its partner Merck & Co has, recently bagging the first US approval for a cytomegalovirus (CMV) therapy in 15 years.
Aicuris now has a €105m ($125m) milestone payment in the bank which, along with an undisclosed royalty stream, could allow the private German group to complete clinical development of at least some of its pipeline alone. Its chief executive, Holger Zimmermann, tells EP Vantage: “Our idea is to build a sustained, integrated biopharma company – we’d like to use the funds to move our projects on.”
However, he will not say whether the anti-infectives specialist will go solo with its next most-advanced candidate, pritelivir. The project is in two phase II trials: one testing a topical formulation in labial herpes, and the other evaluating an oral version in immunocompromised herpes patients resistant to the antiviral acyclovir.
Acyclovir resistance emerges in 4-7% of immunocompromised patients, and the standard of care for this group is foscarnet, an intravenous drug that requires hospitalisation.
As well as providing a more patient-friendly alternative for resistant patients, pritelivir could have an advantage over first-line nucleoside analogues like acyclovir, Mr Zimmermann believes. “Nucs need to be activated by a viral enzyme in order to become active. By definition that means you can only protect cells that harbour the virus, and not uninfected cells.”
Current therapies do not adequately reduce the number of herpes episodes or fully block transmission, according to Aicuris. Pritelivir, meanwhile, is designed to hit the helicase primase enzyme of the virus, a novel mechanism that does not require activation by any viral enzyme, which might translate into improved efficacy versus older drugs.
The project still has a way to go. Phase II results with the topical formulation should be available soon, while the oral trial is due to complete next year.
|Upcoming pritelivir readouts|
|Study||Trial ID||Primary completion|
|Phase II in recurrent herpes labialis vs placebo or Zovirax (Lipp1)||NCT02871492||Aug 2017|
|Phase II in acyclovir-resistant herpes simplex virus infections (Prioh-1)||NCT03073967||Sep 2018|
On the possibility of Aicuris carrying out phase III studies itself, Mr Zimmermann will only say: “It’s a strategic decision, but I think we might have the opportunity to do so.”
And might the group launch pritelivir alone? “It depends on the indication and the region. For some indications it’s probably much better [to have] a partner or out-license it, but if it’s more a specialist thing it might be something a smaller company could do on its own.”
If Aicuris does choose to take the plunge, the experience with Merck and Prevymis could stand the company in good stead.
Prevymis was approved in the US in early November for prophylactic treatment of CMV in patients receiving an allogeneic hematopoietic stem cell transplant (HSCT), and received a positive opinion in Europe soon after.
HSCT patients are not prophylactically given the current gold standard for CMV, ganciclovir, because it can cause bone marrow suppression – “something you clearly do not want after a bone marrow transplant”.
Instead, ganciclovir is used in HSCT pre-emptively, which Mr Zimmermann says differs from prophylaxis given that patients are monitored and treatment is started only if viral load reaches a certain threshold.
He argues that prophylactic therapy is preferable because it can begin straight after transplantation, when the risk of infection is highest. The pivotal trial of Prevymis effectively compared prophylactic versus pre-emptive therapy. “If placebo failed, they were given ganciclovir as a rescue medication.”
After numerous failures in CMV in recent years, Mr Zimmermann is confident that competition is unlikely to come any time soon, at least in the prophylactic arena.
It is now up to Merck whether it attempts to expand Prevymis into other CMV indications, but Mr Zimmermann identifies solid organ transplantation as a logical step. Indeed, he believes that the product “will be useful in any instance where CMV makes problems”, citing HIV and intensive care unit patients as other potential uses.
Prevymis is forecast to bring in $192m by 2022, according to EvaluatePharma sellside consensus – but this is entirely based on the CMV prophylaxis indication.
With Merck now in charge of Prevymis's destiny, Aicuris had better hope that there is still room for its three follow-on CMV candidates, one of which is also licensed to the big pharma.
Mr Zimmermann notes that these projects' mechanisms of action differ from Prevymis. “We clearly do not want to position those drugs against Prevymis – we’re looking for points where we might differentiate them.”
|Prevymis (letermovir)||Cytomegalovirus||Viral terminase complex inhibitor||Approved||Licensed to Merck & Co|
|Pritelivir||Herpes simplex virus||Helicase-primase complex inhibitor||Phase II||Topical and oral version in development|
|AIC649||Hepatitis B||Hepatitis B polymerase inhibitor||Phase I||Potential functional cure|
|AIC476||Cytomegalovirus||Anti-CMV agent||Phase I|
|AIC387||Cytomegalovirus||Anti-CMV agent||Phase I|
|AIC499||Gram-negative infections||Beta lactam antibiotic||Phase I||Supported by Innovative Medicines Initiative|
|AIC284||Autoimmune diseases||IL-2 mutein||Phase I|
|AIC813||Cytomegalovirus||Anti-CMV agent||Preclinical||Licensed to Merck & Co|
|Source: Company website.|