BioPharm Insight

There is rationale for evaluating antifibrotics in COVID-19 given the SARS-CoV-2 virus’ impact on the lungs, but several unknowns persist on the overlap between idiopathic pulmonary fibrosis (IPF) and COVID-19 related fibrosis, making the therapeutic impact of antifibrotics unclear, experts noted. While Fibrogen’s (NASDAQ:FGEN) idiopathic pulmonary fibrosis (IPF) data is strong enough for pamrevlumab to be considered in Phase II, the potential of Blade Therapeutics’ BLD-2660 is tougher to determine given the existence of only in vitro data for the product, they noted.

Rising reports of thromboembolic cases among COVID-19 patients have prompted physicians and also several trials to evaluate higher doses of heparin than are typically used as an anticoagulant strategy, but experts noted there is still a lack of clarity on the optimal regimen. Additionally, they said, while all hospitalized patients stand to benefit from a prophylactic dose, whether to use the higher therapeutic dose in those patients is an open question.

An investigator-led Phase III trial studying hydrocortisone for community-acquired pneumonia has been redesigned to also recruit COVID-19 patients, according to a source familiar with the trial. The France-based study has so far recruited about 300 COVID-19 patients and enrolment is estimated to close in two weeks, he added. As of today (7 April), France has 98,984 confirmed cases and 8,911 deaths.

Seattle Genetics’ (NASDAQ:SGEN) tisotumab vedotin needs to show longer responses in metastatic cervical cancer patients in a Phase II study than those previously seen in Phase I/II data in order to prove clinical significance and potentially support approval, experts said.

Lexicon Pharmaceuticals (NASDAQ:LXRX) and Sanofi’s (EPA:SAN) Zynquista (sotagliflozin) has experts reserving judgement on the drug’s value without a direct comparison to SGLT2 inhibitors following topline data in type 2 diabetes (T2D) patients with chronic kidney disease (CKD).

Improving patient identification tools will be key to getting full market traction for Merck KGaA’s (ETR:MRK) tepotinib and Novartis’ (SIX:NOVN) capmatinib after an expected approval in non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping mutations, experts said. Presentations at ASCO earlier in June on initial Phase II data for both drugs were impressive, however, with experts citing interest in using the drug in the first-line (1L) setting.

Pfizer’s (NYSE:PFE) Xeljanz (tofacitinib) safety alert in rheumatoid arthritis (RA) patients could lead to exclusion of riskier ulcerative colitis (UC) patients from receiving the 10mg BID dose, some experts said, while others noted the need for more data to influence treatment decisions.

A new US Department of Health and Human Services (HHS) proposal to curb rebates will increase biosimilar competitiveness, and positively impact low-cost and generic alternatives in the hepatitis C (HCV) and diabetes spaces, experts said. The latter are currently given lower formulary priority compared to high-cost branded alternatives in Medicare Part D plans, they explained.

Roche’s (SIX:ROG) cobas EGFR Mutation Test v2 liquid biopsy diagnostic used with and after initial treatment with its own drug Tarceva (erlotinib) is becoming increasingly redundant as more physicians choose AstraZeneca’s (LON:AZN) Tagrisso (osimertinib) for first-line (1L) treatment of EGFR mutant non-small cell lung cancer (NSCLC).

Bristol-Myers Squibb’s (NYSE:BMY) bid for Opdivo (nivolumab) and Yervoy (ipilimumab) as a maintenance therapy following chemotherapy in small cell lung cancer (SCLC) will likely be thwarted by the expected addition of Roche’s (SIX:ROG) Tecentriq (atezolizumab) to the first-line (1L) setting, experts said.

Novartis’ (VTX:NOVN) outcome-based contracts (OBCs) for reimbursing its CAR-T therapy Kymriah (tisagenlecleucel) for acute lymphoblastic leukemia (ALL) remain a viable option for treatment centers, despite recent conflicting media reports saying otherwise, experts said. But private payer enthusiasm for engaging in OBCs and how the arrangement can overall reduce healthcare costs is unclear in light of nebulous financial logistics, they noted.

AstraZeneca’s (LON:AZN) Fasenra (benralizumab) failures in chronic obstructive pulmonary disease (COPD) could be due to the antibody’s activity being limited to only those patients with an asthma-COPD overlap syndrome (ACOS) phenotype, where the drug’s use could be further explored, said experts.

Jounce Therapeutics’ (NASDAQ:JNCE) JTX-2011 mechanism as an inducible T-cell co-stimulator (ICOS) agonist holds promise to spur immune responses in gastric and breast cancer, experts said. However, the absence of validated clinical data draws pause on forecasting Phase I/II trial success, they noted.

AstraZeneca’s (LON:AZN) benralizumab will likely have a dosing advantage over competitors in severe eosinophilic asthma, but may struggle to reach optimal market expectations, experts said. Convincing some physicians that it offers a superior efficacy profile for the majority of patients will be the major challenge, experts said.

Pfizer (NYSE:PFE) and Merck KGaA’s (ETR:MRK) Phase III first-line advanced renal cell carcinoma (RCC) JAVELIN 101 study of PD-L1 inhibitor Bavencio (avelumab) in combination with Pfizer’s Inlyta (axitinib) met its initial recruitment target of 583 patients in summer 2017, said a source familiar with the trial.

Global Blood Therapeutics’ (NASDAQ:GBT) GBT440 has a mixed Phase II outlook in idiopathic pulmonary fibrosis (IPF) patients due to challenges in recording accurate improvements in oxygen saturation and clinical translation of such changes, expert said.

Coherus’ (NASDAQ:CHRS) latest motion to stay legal proceedings with Amgen (NASDAQ:AMGN) for its Neulasta (pegfilgrastim) biosimilar faces an unclear court decision -- on which the company hinges financially -- but may find favor if the court decides to conserve resources, said experts.

Experts said it is not clear if courts will accept Coherus’ recent motion to stay, filed last week, on its prior motion to dismiss Amgen’s patent infringement case —a bid to conserve funds until a final approval.

Despite the broad label received in recent ovarian cancer approvals, experts said they are still considering using homologous recombination deficiency (HRD) tests to whittle down eligible patients before treatment.

Tesaro’s (NASDAQ:TSRO) Zejula (niraparib) was the first PARP inhibitor to be given a broad label for second-line ovarian cancer maintenance therapy, while Clovis Oncology’s (NASDAQ:CLVS) Rubraca (rucaparib) is also anticipated to have a similar label.

Roche’s (VTX:ROG) slim benefit with Perjeta (pertuzumab) in the APHINITY trial in Her2+ breast cancer has experts predicting a smaller than anticipated market use in the adjuvant setting including the more hopeful higher risk subset.

Roche had earlier announced the trial reaching its primary endpoint on 2 March, leading to an upward share price movement of 6.5% and expectations of Perjeta being added to the standard of care -- Roche’s (VTX:ROG) Herceptin (trastuzumab) and chemotherapy -- for adjuvant therapy in Her2+ patients.

GlaxoSmithKline’s (LON:GSK) closed triple FF/UMEC/VI combination carries dampened enthusiasm for use in chronic obstructive pulmonary disease (COPD)with questionable risk/benefit profile of the inhaled corticosteroid (ICS), experts said.

The closed triple is a once-daily inhaler with an inhaled corticosteroid (ICS)/long acting muscarinic antagonist (LAMA)/ long acting beta agonist (LABA) combination of GSK’s Flovent (fluticasone), Incruse (umeclidinium) and vilanterol, respectively.

Mylan's (NASDAQ: MYL) bid for approval of MGR001—generic of GlaxoSmithKline’s (LON:GSK) Advair (fluticasone/salmeterol) inhaler—is within reach but dependent on the data-package’s precision to specific FDA guidelines introduced in 2013, said experts.

AstraZeneca’s (LON:AZN) Lynparza (olaparib) is not exhibiting an alarming level of secondary malignancies, said experts based on an FDA adverse events (AEs) document this news service obtained through a Freedom of Information Act (FOIA) request.

The risk for secondary malignancies developing due to Lynparza treatment was a concern for the Advisory Committee that reviewed the drug’s maintenance treatment approval application.

Pfizer's (NYSE:PFE) Sutent (sunitinib) may face uptake barriers in the adjuvant setting for renal cell carcinoma (RCC) due to its side-effect profile despite the Phase III S-TRAC study reaching its primary endpoint, said experts.

In the absence of any approved adjuvant therapies, the S-TRAC trial' (NCT00375674) improving disease-free survival (DFS) is significant, said experts. It is nonetheless surprising, they noted, since the previous NCI-led Phase III ASSURE trial (NCT00326898) of Sutent as an adjuvant therapy did not reach its DFS primary endpoint.

Roche's (VTX:ROG) Perjeta (pertuzumab) spurs confidence in experts about its success in the adjuvant setting APHINITY trial for HER2-positive (HER2+) breast cancer but with a pause due to statistical complexities.

Neoadjuvant trials are said to be largely predictive of success in the adjuvant setting, according to an analyst report. While experts agreed they also cautioned against extrapolating neoadjuvant results, owing to the complexity of large trials.

Off-label prescribing and drugs used for multiple oncology indications will complicate efforts to consolidate billing codes under Medicare Part B per recommendations from a legislative-branch agency, experts said.

Under recommendations issued in a 15 June report by the Medicare Payment Advisory Commission (MedPAC), cancer drugs will be disproportionately affected by the consolidation, they explained. Nonetheless, other drugs covered under Part B for indications like autoimmune diseases, chronic obstructive pulmonary disease (COPD) and others will also be impacted, they noted.

Clovis Oncology's (NASDAQ:CLVS) scope with rucaparib may be limited to use in ovarian cancer patients with BRCA mutations, said experts, though rucaparib investigators were less pessimistic.

The change in the cutoff for loss of heterozygosity (LOH) led to a subdued outlook for identifying non-BRCA responders, as was earlier envisioned with the development of the LOH assay, several experts noted. However, Ariel2 investigators emphasized that that the intent of the preplanned analysis was to develop a better tool to identify responders, and refining the LOH score allowed that.

Medivation's (NASDAQ: MDVN) Phase II ABRAZO trial with talazoparib in metastatic gBRCA mutant breast cancer patients was closed for enrollment before it reached its target, to allow focus on the ongoing Phase III EMBRACA trial, said an investigator.

Astellas Pharma (TYO:4503)/Medivation's (NASDAQ:MDVN) prostate cancer drug Xtandi (enzalutamide) has drawn debate from Capitol Hill experts on whether the National Institutes of Health (NIH) will hold a hearing to address its price. Most doubted the government agency would weigh in on the controversial topic whilst others said it's possible in an election year.

Novartis' (VTX:NOVN) buparlisib faces an uphill battle in improving overall survival (OS) in the BELLE-2 Phase III breast cancer trial to an extent that it would justify its side-effect profile, said experts. Targeting the PI3K pathway as buparlisib does would cause significant side effects, since it is involved in a number of cellular functions, experts said. The number of patients that discontinued treatment due to side effects adversely affected the drug's risk-benefit profile, they added.

Immunomedics' (NASDAQ:IMMU) clivatuzumab exhibits potential as a third-line therapy in pancreatic cancer, experts said, while noting that an overall survival (OS) of two months over the control arm would be clinically significant. Yet the slew of failed trials in this space warrants caution regarding Phase III success, they added.

Exelixis' (NASDAQ:EXEL) Cometriq (cabozantinib) faces uptake challenges due to competition with existing drugs and investigational immunotherapy, but may find a niche in smaller patient subsets, said experts.

Pfizer's (NYSE:PFE) Xeljanz (tofacitinib) is likely to be approved in moderate-to-severe plaque psoriasis but market uptake will be poor due to competition from other drugs and pricing, experts agreed.