When Johnson & Johnson highlighted 12 potential blockbusters from its pipeline in May there were a few on the list that raised eyebrows. Two of these – the flu project pimodivir and the respiratory syncytial virus candidate lumicitabine – are in a sector where the company is not currently well known: infectious diseases.
“It’s a new area to J&J to a certain extent,” Julian Symons, head of Janssen’s respiratory infections division, tells EP Vantage. “But it’s a huge unmet medical need, and all our medicines are first-in-class agents.” J&J still has a long way to go, however, before it can show that these assets live up to its lofty expectations.
New in flu
The unit has four clinical-stage projects, the most advanced of which is the Vertex-originated flu candidate pimodivir, which recently yielded positive data from the phase II Topaz trial in outpatients (Snippet roundup: Novartis enters Advair generic race, Biogen dealt CFO blow, June 16, 2017).
But J&J’s main focus is on hospitalised patients who currently do not have any treatment options. “390,000 people are hospitalised with influenza in the US every year, and no drugs have been approved for that patient segment,” says Mr Symons.
Roche’s Tamiflu, which has the go-ahead for acute, uncomplicated flu, is often also used in the hospital but its efficacy here has not been proven. Still, J&J studied pimodivir as an add-on to Tamiflu in Topaz and is taking a similar approach in its second phase II study, in hospitalised patients, which is due to report data this year.
The latter trial will be more important for gauging pimodivir’s chances – so far, the project has flown under the radar, with EvaluatePharma sellside consensus seeing sales of just $19m in 2022. Mr Symons admits that this has not garnered much attention, but says this could soon change. As more data emerge, he says: “I think the profile of the compound will increase over the next six months.”
Phase III studies are slated to start in the second half of this year, but the design has not yet been finalised so Mr Symons will not say whether pimodivir will be going head to head against Tamiflu or in combination with it.
Giving the products together makes sense because they have a different mechanism of action. “Neuraminidase inhibitors [like Tamiflu] work by preventing that very final step in the lifecycle of the virus. Our approach is to go much earlier in the lifecycle and inhibit the viral polymerases,” Mr Symons explains.
J&J is also working on an internal project, JNJ-5806, that could be combined with pimodivir. Both assets target viral polymerase, which is vital for the replication of the flu virus genome, but hit different components: pimodivir inhibits PB2 while JNJ-5806 acts against the PA subunit.
“In vitro at least, we see very nice synergistic activity between these two compounds,” says Mr Symons.
J&J has carried out a phase I study of the combination in healthy volunteers and plans to progress this into phase II – but does not intend to take JNJ-5806 forward as a monotherapy, he adds.
|J&J’s clinical-stage respiratory infection projects|
|Pimodivir||Influenza A||PB2 inhibitor||Phase II||Hospital study (NCT02532283)|
|Lumicitabine||Respiratory syncytial virus||RSV nucleoside analogue||Phase II||Adult phase II (NCT02935673); Paediatric phase I (NCT02202356)|
|JNJ-5806||Influenza||PA inhibitor||Phase I||Pimodivir combo (NCT02888327); Challenge study (NCT02588521)|
|JNJ-678||Respiratory syncytial virus||RSV fusion inhibitor||Phase I||-|
J&J’s other main focus for this business is respiratory syncytial virus (RSV), where it is developing what it believes is another potential blockbuster, lumicitabine, gained through the 2014 purchase of Alios Biopharma. This is in phase I in children and phase II in adults who have been hospitalised with the virus.
Drug development in RSV has proven tricky but, as with flu, there is a large untapped market for any product that does succeed. Most infants contract the virus before their second birthday and, while many cases are mild, a “significant number” end up in hospital, according to Mr Symons. Elderly and immunocompromised people are also at risk, and overall the virus “probably causes at least as many hospitalisations as influenza”.
Once again, analysts remain cautious about lumicitabine’s prospects, with EvaluatePharma putting 2022 sales at $27m. Still, it is a reflection of the state of the RSV pipeline that this would still make it the fourth-biggest product in the disease. Also featuring is Novavax’s RSV F Vaccine, in spite of its phase III failure last year.
|Top five RSV products in 2022|
|Global sales ($m)|
|RSV F Vaccine||Novavax||RSV vaccine||Phase III||-||360|
|Suptavumab||Regeneron Pharmaceuticals||Anti-RSV MAb||Phase III||-||79|
|Lumicitabine||Johnson & Johnson||RSV nucleoside analogue||Phase II||-||27|
|MEDI8897||AstraZeneca||Anti-RSV MAb||Phase II||-||6|
J&J is also taking a dual approach in RSV. Lumicitabine is a nucleoside analogue designed to prevent viral replication, while its second RSV project, JNJ-678, is an RSV fusion inhibitor that aims to stop the virus getting into a patient’s cells. Combination studies are on the company’s radar, Mr Symons says – possibly in patients undergoing bone marrow stem cell transplant, who have a high level of mortality with RSV.
As for the future of the respiratory infections unit, J&J has earlier-stage projects in development for rhinovirus and coronaviruses such as Sars and Mers, according to Mr Symons. Perhaps it can uncover new potential money-spinners in these areas. First, though, it has work to do to make its current candidates a success.