Friday Five - The week in review

The FDA invites Gilead to the CAR-T PAR-T

Gilead Sciences' Yescarta is the second CAR-T therapy to be approved for use in the US market, specifically as a treatment for refractory diffuse large B-cell lymphoma (DLBCL). Following Gilead's $12-billion acquisition of Kite Pharma in August, approval marks an important – if not unexpected – regulatory breakthrough. The onus will now be on Gilead to prove it can successfully operate at the cutting edge of the oncology market. Yescarta's label notes that 72 percent of patients treated in the ZUMA-1 trial had an objective response rate and 51 percent benefited from complete remission.

See ViewPoints: And so it begins- Gilead's CAR-T approval sets off the cell therapy race

A list price of $373 000 per patient (for a one-off treatment) has been set for Yescarta, which seemingly undercuts the price of Novartis' Kymriah, which was approved as a treatment for paediatric leukaemia in August and costs $475 000. There are, however, a number of factors to consider; primarily Novartis' promise that patients won't be charged for Kymriah if they fail to respond to treatment after a month and the notably smaller patient population eligible for treatment.

Respective prices will converge further when labelling for both Kymriah and Yescarta is expanded and both products are approved for identical indications. Broader use will also determine the commercial success of these products; while both approvals have shifted the paradigm in cancer care, near-term annual revenues will do little to move the needle at either Novartis or Gilead.

See also – ViewPoints: Is outrage over drug pricing sustainable- at least, as far as investors are concerned?

One in the eye for Allergan

It is probably fair to say that Allergan's efforts to shore up intellectual property protection on its Restasis franchise have backfired spectacularly.

Last month, the company struck a controversial agreement with the St. Regis Mohawk Tribe, whereby Allergan paid it $13.8 million to assume control of its Restasis patents and use its sovereign immunity protection as a defence in an ongoing inter partes review (IPR) challenge. Allergan has argued in favour of this approach by claiming that IPR challenges are unconstitutional, but the company has attracted significant backlash. Speculation has abounded that the drugmaker was willing to take on the risk because it was confident in a positive outcome for a separate lawsuit ongoing in a district court; by winning at the district level and also making itself exempt from IPR, it would likely see Restasis protection continue through to 2024.

Instead, the company is contending with the worst of both worlds; a federal judge ruled against Allergan on Monday, invalidating four Restasis patents on grounds of obviousness and rendering moot much of the bad publicity it has generated by seeking out the tribal deal. The presiding judge added insult to injury; while sovereign immunity was not a factor in the federal case, he wrote that he has "serious concerns" about the validity of Allergan's "tactic."

See ViewPoints: Well that was fast- Allergan patent debacle looks to quickly close the door on sovereign immunity deals

The Cabometyx comeback continues

With immunotherapies playing an increasingly dominant role in the cancer market, it is hard not to be impressed by the continued performance of Exelixis and Ipsen's Cabometyx. Approved for the treatment of thyroid cancer and second-line renal cell carcinoma (RCC), the targeted small-molecule therapy is heading towards approval in first-line RCC and looks well positioned as a future treatment for refractory hepatocellular carcinoma (HCC).

The latter indication represents positive upside if a relatively niche commercial opportunity, note analysts, with returns in first-line RCC potentially much larger. In some quarters, Cabometyx has been largely written off at the expense of Bristol-Myers Squibb's Opdivo and Yervoy combination, but clinical data suggests there is an opportunity for Exelixis and Ipsen's drug to also be used as a first-line therapy; a view supported by its recent adoption into NCCN guidelines some months ahead of potential approval in February – ViewPoints: Exelixis, Ipsen's Cabometyx continues to defy expectations.

Failure in a pivotal-stage prostate cancer study back in 2014 – an event which prompted Exelixis to slash 70 percent of its workforce – provides additional backdrop for Cabometyx's continued revival.

See also – KOL Views: Exelixis, Ipsen’s Cabometyx succeeds in refractory HCC – can it be more than a niche product?

Niche lung cancer indications take spotlight at WCLC

With a number of pivotal-stage studies set to read out over the next six months, new data will provide a clearer indication as to how the market for metastatic non-small-cell lung cancer (NSCLC) therapies will evolve; the key question being whether PD-(L)1 inhibitor and chemotherapy combinations or PD-(L)1 and CTLA-4 inhibitor pairings provide definitive results that will allow dominance of this treatment space.

In the meantime, standout data presented at this week's World Conference on Lung Cancer (WCLC) in Japan focused on smaller lung cancer indications, namely patients whose tumours harbour ALK and ROS-1 mutations.

In the former, Roche looks set to dominate in the first-line setting, forcing Pfizer into a position of market retreat – Spotlight On: Pfizer's efforts to stay relevant in ALK-positive lung cancer. One it is looking to offset with a rapid approval of lorlatinib, a follow-up to its previous first- and best-in-class treatment Xalkori. Pfizer will be looking to sweep into the second-line setting and also targeting the smaller indication of ROS-1 positive NSCLC, although in this market it could face competition from Ignyta's entrectinib – ViewPoints: Ignyta takes on Pfizer in niche lung cancer segment.

Novo Nordisk gets thumbs up for key diabetes drug

Novo Nordisk looks set to secure US approval for its next-generation GLP-1 agonist semaglutide following a positive advisory committee meeting this week. This should allow the company to build on its market-leading position with Victoza and provide notable competition to Eli Lilly's Trulicity, note analysts.

Wary of repeating the previous two-year delay for its insulin treatment Tresiba, this week's AdCom was no forgone conclusion. One Phase III study had indicated an imbalance in diabetic retinopathy incidence; a finding which if replicated in additional trials would potentially kill semaglutide as a viable therapy, one key opinion leader recently noted to FirstWord. The FDA, however, while referencing the findings for discussion, appears not overly concerned and argue these data should not impact how semaglutide is used. Approval and launch of semaglutide are now the key future events for Novo Nordisk, but will be followed quickly in 2018 by initial readout of Phase III data for an oral version of semaglutide. If positive, that product could have a seismic impact on the diabetes market.

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