Harmony Biosciences Holdings, Inc. (HRMY) Earnings Call Transcript & Summary

Good morning. My name is Ashley, and I will be your conference operator today. At this time, I would like to welcome everyone to Harmony Biosciences Phase III INTUNE study top line results conference call. [Operator Instructions] Please be advised that today's conference call may be recorded. [Operator Instructions] I will now turn the call over to Luis Sanay, Head of Investor Relations. Please go ahead.

Thank you, operator. Good morning, everyone, and thank you for joining us today to discuss the top line results from the Phase III INTUNE study. Our speakers on today's call are Dr. Jeffrey Dayno, President and CEO; and Dr. Kumar Budur, Chief Medical Officer. Following our prepared remarks, Sandip Kapadia, Chief Financial Officer and Chief Administrative Officer, will also be available for the Q&A portion of the call. During today's call, we will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties. Our actual results may differ materially, and we undertake no obligation to update these statements even if circumstances change. We encourage you to consult the risk factors referenced in our SEC filings for additional details. I would now like to turn the call over to Dr. Jeffrey Dayno. Jeff?

Thank you, Luis, and good morning, everyone. I also want to thank you for joining our call this morning and for your interest in Harmony and the top line results from the INTUNE study. First, I would like to take a moment to thank all the patients and their families and the clinical investigators and their staff who participated in the INTUNE study, along with all of my colleagues at Harmony, who oversaw the conduct of this trial and supported the patients and clinicians who are involved in the trial. Based on our initial read of the top line data from the INTUNE study, we are encouraged by the magnitude of the response that patients experienced in the initial open-label treatment period and by the totality of the data thus far that clearly shows patients with IH experienced a positive clinical effect with pitolisant. In fact, almost 90% of the patients who completed the trial elected to continue into the long-term extension trial. Although the separation between pitolisant and placebo did not reach statistical significance on the primary endpoint during the randomized withdrawal phase of the trial, there was a positive trend for pitolisant on this endpoint as well as many of the prespecified secondary endpoints, including the idiopathic hypersomnia severity scale and the sleep inertia questionnaire. As you know, the INTUNE study completed enrollment 9 months ahead of plan, reflecting the significant interest from both the patient and health care professional communities. We also received orphan drug designation for pitolisant for the treatment of idiopathic hypersomnia, reflecting the FDA's interest in the potential utility of pitolisant in patients with IH. And based on our careful listening to the IH community, we know that they have a strong desire for a non-scheduled treatment option to treat their IH symptoms. We remain committed to the IH patient community and pursuing an indication for pitolisant in IH. At this point, we will continue our review with the full data set, which will inform the path forward. We believe that based on the totality of the evidence that we have seen thus far, along with pitolisant receiving orphan drug designation for IH, there is an opportunity for us to work with the FDA on a path forward for pitolisant in idiopathic hypersomnia. Once we have completed our review of all the data, we look forward to engaging with the agency. I will now turn the call over to Dr. Kumar Budur, our Chief Medical Officer, to provide additional details on the INTUNE study. Kumar?

Thank you, Jeff. Good morning, everyone, and thank you for joining the call. I'd like to echo Jeff's comments in thanking those who participated in the INTUNE study, and I'm also encouraged with the totality of the data that clearly showed patients experienced a positive clinical benefit with pitolisant. I would like to start my comments with a brief overview of the study design. The INTUNE study was a placebo-controlled, double-blind, randomized withdrawal trial, conducted in adult patients with idiopathic hypersomnia at 52 clinical trial sites across the U.S. The primary objective was to evaluate the safety and efficacy of pitolisant compared with placebo in treating excessive daytime sleepiness in patients with idiopathic hypersomnia. The secondary objectives were to assess the impact of pitolisant on other important aspects of idiopathic hypersomnia, such as idiopathic hypersomnia severity, daytime functioning and cognitive performance. Other outcome measures include patient impression of overall change in symptoms and investigator assessment of overall disease severity. The study itself consisted of 2 periods, a 8-week open-label period consisting of 3 weeks of dose titration, 3 weeks of dose optimization and 2 weeks of stable dose period followed by a 4-week double-blind randomized withdrawal period to assess the primary, key secondary and other endpoints. During the open-label period, all patients were treated with pitolisant for 8 weeks and 83% of the patients -- that's 83% of the patients who completed the 8-week open-label period, were considered as treatment responders as defined by [ 3 ] or higher point improvement in Epworth Sleepiness Scale. A total of 139 patients were randomized in the double-blind randomized withdrawal phase, where half of them continued to receive pitolisant, while the other half received placebo. On-efficacy assessments were measured from the end of stable dose period to end of randomized withdrawal period and analyzed to compare the differences between the pitolisant group and the placebo group. Now moving on to the data. We are very encouraged by the magnitude of response seen in the initial open-label treatment period, with 83% of the patients completing this period responded with an average of 9.4 points improvement in the Epworth Sleepiness Scale. A positive trend favoring pitolisant was observed during the 4-week double-blind randomized withdrawal period. However, no statistically significant difference was observed between pitolisant and placebo group on the primary endpoint of ESS. Positive trends favoring pitolisant were also observed across all 3 specified endpoints, including the idiopathic hypersomnia severity scale, which approached statistical significance as well as other endpoints, including PROMIS SRI, [indiscernible] and sleep inertia questionnaire. Equally encouraging is the number of patients that's almost 90%, almost 90% who completed the randomized withdrawal period elected to continue into the 12-month long-term extension study, which is currently ongoing. Importantly, the safety and tolerability profile of pitolisant was consistent with the established safety profile of pitolisant and no new safety segments were observed in adult patients with idiopathic hypersomnia. As Dr. Jeff Dayno mentioned earlier, we remain committed to the idiopathic hypersomnia patient community, and we understand their strong desire for a non-scheduled treatment option for idiopathic hypersomnia. Following the thorough review of the full data set, we will work closely with the FDA to discuss next step and a path forward for pitolisant in idiopathic hypersomnia. We look forward to sharing additional information in the future. In closing, I would like to thank all the patients and their family members who participated in the study as well as the clinical investigators and site personnel for their efforts and commitment in helping us advance this development program. I would also like to thank the patients advocacy group for this relentless efforts on behalf of patients with idiopathic hypersomnia. I'll now turn the call over to the operator to start the Q&A session. Operator?

[Operator Instructions] We'll take our first question from Charles Duncan with Cantor Fitzgerald.

Congrats on the responder rate, but the randomized withdrawal makes this a little bit more complex to interpret. So I guess I'm wondering what do you -- what rate of relapse had you assumed in the randomized withdrawal portion? And in terms of next steps, could you imagine conducting a new trial with the parallel group design or give us a little bit of color on the timing of your discussions with the agency and path forward?

Yes. Sure, Charles. Thanks for the question. With regards to -- yes, I think that the initial -- we were very pleased and encouraged by the magnitude of the response, as you mentioned, 83% as well as the range of response almost a 10-point improvement on the upper scale in the open-label phase. As for what we have seen initially and it's early in the randomized withdrawal phase as we keep sort of going through the data, the placebo response group and the sort of the worsening of about 4 points was not consistent with the expectations of what we thought in that group. So the dynamic during the 4-week randomized withdrawal phase is obviously what we are looking at much more closely as we go through the full data set. And I think that based on that, it's really -- it's too early to -- we are just going through the full data set, and that's for next steps with the agency. We'll provide an update on that after the full data analysis. I think we're encouraged with regards to what we've seen thus far in the data with regards to the robust effect in the open-label phase and up to 90% of patients electing to go into the long-term extension study. So I think what it tells us is a positive clinical effect overall in this patient population that we've seen. And along with pitolisant receiving orphan drug designation by the FDA, we're encouraged that we'll have a step forward. And obviously, we'll provide an update on that at that time.

Okay. That's helpful. If I may, one follow-up, and that is regarding that open-label extension study or phase of the study. I'm intrigued to about what -- not only the interest in rolling over but also the persistent. So first of all, with regard to the control patients in the randomized withdrawal, are they given an opportunity to restart pitolisant? And then secondarily, what have you seen in terms of persistence within the open-label extension for those patients currently on pitolisant?

Yes, sure, Charles, great question. I'll turn that over to Kumar to respond to that one.

Yes. Charles, thanks for the question. The long-term extension study was always in the plan, along with the main study. So all patients who completed the randomized withdrawal period were offered an opportunity to participate in the long-term extension study. And as I mentioned earlier, almost 90% of the patients elected to participate in the long-term extension study. The study is ongoing, and we have seen very little attrition in the long-term extension study. We are collecting safety and efficacy data from the long-term study as well. And those data will be available in due course of time.

But -- I'm sorry to be dense, but the patient -- I guess, all patients were -- had an opportunity to continue on the pitolisant in the long-term extension even if they were on the, call it, controller placebo arm in the randomized withdrawal?

[indiscernible], Charles. So whoever completed the randomized withdrawal portion of the study, whether they were on placebo or pitolisant, because when they complete the study, we wouldn't know what they were taking because the study was still ongoing at that time. They were given an opportunity to participate in the long-term extension study and they started on pitolisant at 8.9, titrated to 17.8 and [ 35.6 ] based on their tolerability and efficacy response.

We will take our next question from François Brisebois with Oppenheimer.

Just -- so I was just wondering in terms of the randomized withdrawal, can you just help us understand maybe the thought process behind using that study design?

Yes. Frank, so I think that with regards to the randomized withdrawal design, with idiopathic hypersomnia being a sort of adjacency to narcolepsy, the thinking is once the efficacy is established -- has been established with pitolisant in narcolepsy, then a randomized withdrawal design is available with regards to an enriched design -- what is thought to be an enriched design looking at maintenance of effect. Obviously, I think as you're aware, there's precedent with IH in the space based on the trial that Xywav conducted and regulatory sort of precedent there. So the thinking was with a randomized withdrawal and enriched design, it would give us the opportunity to demonstrate an open label on the effect there and then the benefit with regards to going forward. What -- as I mentioned before, given the mechanism of action of pitolisant, which is different than some of the other agents in this class, the way that we saw in the randomized withdrawal phase in the placebo group did not have as much of the worsening over that time as was expected. And we're -- obviously, we're looking into that more closely in terms of that dynamic and why that was the case. But the overall thinking was an enriched design opportunity to assess the efficacy and safety of pitolisant in this patient population. Kumar, any additional thoughts?

No, I think you've covered everything, Jeff. And also the minimizing the number of patients who are on placebo and to the extent they will be on placebo that also played into our -- played a role into the randomized withdrawal study design. As we mentioned earlier, it's just that the response rate in the open-label period, 83%, not only the response rate, but the magnitude of response of 9.4% from baseline was pretty impressive. But in the randomized withdrawal period, we are looking into the factors that could have potentially affected the rate at which placebo arm declines. So we are evaluating those data further.

Okay. And if I could just sneak in a follow-up here. Are you guys ready to discuss hypotheticals of what could have happened to the placebo arm that maybe didn't happen and we talked about other trials, maybe in Xywav or whatnot? Or are we -- are you guys just going to look through the data more before you're ready to discuss maybe hypotheticals of the placebo response? And then just on that back, with the FDA open, how important in a disease like this with -- what the treatment options that are out there or the treatment option that's out there is open-label data, you think, to the FDA?

Sure, Frank. So I think that with regards to your question, and it's early, and I don't want to speculate. But some of the thinking in the design -- in the randomized withdrawal period, we actually extended to a full 4 weeks in the randomized withdrawal period. The thinking of that was we knew that the mechanism of action of pitolisant sort of being different. Obviously, the other study conducted with Xywav and in oxybate. The mechanism of action is different with regards to histamine modulation. And from a pharmacodynamic perspective, the potential with regards to patients coming off of active drug, pitolisant, in the open-label phase, how long it would take with regards to experiencing the placebo response and washing out. So that's some early thinking that we are digging into the data, looking at the trend over that 4-week period. With regards to open-label data, I think that as we talked about the totality of the data and the trends, not only in the primary endpoint, but the key secondary outcomes, namely the idiopathic hypersomnia severity scale that approach significance and along with the overall benefit risk profile of pitolisant and as a non-scheduled treatment option. So after review of all the data and all these factors, we will work with the agency. And I think we're optimistic in terms of identifying a path forward, and we're committed to pitolisant and in the IH patient population and pursuing the indication.

We'll take our next question from David Amsellem with Piper Sandler.

So I just wanted to switch gears a little bit and get your thoughts on commercial implications here, given the overlap between NT2 and IH in terms of how patients present in symptoms. So do you think that there is the potential that this could -- that physicians could interpret the data in a way that perhaps has been putting the brakes on further usage or significant usage in the NT2 subgroup? And just how do you think about that from a commercial perspective to the extent that there is any ill effects?

Yes. David, thanks for the question. I mean I think at this point, IH is a distinct diagnosis with regards to diagnostic codes, first of all, differentiating IH from NT2 and then the diagnostic criteria with regards to IH versus NT2 based on the ICSD III criteria. So I think that -- and with regards to in a clinical trial, part of the inclusion/exclusion criteria. So that -- the initial thinking is the populations are distinct. And with regards to the overall response and the meaning of the data, it's obviously still early as we explore the full data set. So we're not -- at this point, this is an idiopathic hypersomnia patient population. And I think I can have Kumar comment with regards to the study population that we were investigating aside from -- in terms of the commercial impact.

Thank you, Jeff, and thank you, David, for the question. Yes, as Jeff mentioned, idiopathic hypersomnia is a distinct ICSD III diagnostic category with a clear characteristic features and those were our inclusion/extrusion criteria in the clinical trial. And if you look at the baseline characteristics of our study, these are the patients who had a diagnosis of idiopathic hypersomnia and any NT1 or NT2 patients were clearly excluded from the study. And even in this patient population, granted that the primary endpoint did not separate during the randomized withdrawal period, but the totality of the data that I alluded to earlier in terms of the open-label period where 83% of the patients showed response and the response was defined as greater than are equal to 3 points improvement in ESS score, which, by the way, is larger than what AASM guidelines suggest, which is a 2-point change is considered as clinically meaningful and also the magnitude of response, which is 9.4 points from baseline to the end of open label period is pretty impressive. And also in the randomized withdrawal period, as Jeff alluded to earlier, idiopathic hypersomnia severity scale, which actually measures all aspects of idiopathic hypersomnia, it approached almost statistical significant and all the other endpoints like PROMIS SRI, [indiscernible], sleep inertia questionnaire, they are all trended in a favorable direction to pitolisant and, of course, the long-term extension study where we have almost 90% of the patients electing to participate in that study. So the totality of the data in idiopathic hypotonia is encouraging, and we are evaluating this data further, especially in the random withdrawal period, to see -- to basically better understand the data.

Yes. [indiscernible].

If I may...

Yes. Go ahead, David.

Yes. If I may sneak in a follow-up, I mean -- and I might have missed this. Can you comment on background medications and how that could have been a confounding factor here?

Yes, sure, David. So I think that -- so patients were allowed in the trial on background medications as long as their baseline level of sleepiness met the inclusion/exclusion criteria. So that is an important follow-on analysis that is being conducted along with others with regard to the impact of other potential confounders. But to your original question, I think that in terms of real-world treatment and real-world management, we're encouraged with regards to in the open-label phase. We've got the magnitude of response that Kumar shared, 83% responders close to a 10-point improvement in sort of open-label real-world dosing in this patient population as well as the interest of patients of around 90% electing to go into the long-term extension. So with regards to a clinical effect, outside of the 4-week randomized withdrawal phase that we're obviously digging in real hard to the full data set. We're encouraged by that clinical response, and whether it's patients with IH or overlap with NT2, I think that's our current sort of position on this.

We'll take our next question from Graig Suvannavejh with Mizuho.

I was wondering -- I didn't -- I think I didn't see a key value included in the press release. I was wondering if you could share what the P value was? And also, if you could share what the exact placebo response rates so we can kind of assess what the delta was? And lastly, a question around if you have any additional data cuts from this study before you have a chance to meet with FDA?

Sure, Graig. Kumar, would you like to respond to that?